Haaga - CT and MRI of the whole body 6th Ed. [2017]

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CT AND MRI OF THE WHOLE BODY

VOLUME I

CT AND MRI OF THE WHOLE BODY Sixth Edition John R. Haaga, MD, FACR, FSIR, FSCBT, FSRS Gold Medalist AARS and SCBTMRI Professor of Radiology Case Western Reserve University School of Medicine Emeritus Chairman and Professor of Radiology University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio

Daniel T. Boll, MD, FSCBT Professor of Radiology Section Chief Abdominal and Oncologic Imaging University Hospital of Basel Basel, Switzerland

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

CT AND MRI OF THE WHOLE BODY, SIXTH EDITION

ISBN: 978-0-323-11328-1 Volume 1 Part Number: 9996117383 Volume 2 Part Number: 9996117324

Copyright © 2017 by Elsevier, Inc. All rights reserved. The copyright for chapter 2 is owned by the author, Mark Patrick Supanich. Seth Kligerman retains right for his original images. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher, except that, until further notice, instructors requiring their students to purchase CT and MRI of the Whole Body by John R. Haaga, MD, may reproduce the contents or parts thereof for instructional purposes, provided each copy contains a proper copyright notice as follows: Copyright © 2017 by Elsevier Inc. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this ield are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identiied, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2009, 2003, 1994, 1988, and 1983. Library of Congress Cataloging-in-Publication Data Names: Haaga, John R. (John Robert), 1945- , editor. | Boll, Daniel T., editor. Title: CT and MRI of the whole body / edited by John R. Haaga, and Daniel T. Boll. Description: Sixth edition. | Philadelphia, PA : Elsevier, [2017] | Includes bibliographical references and index. Identiiers: LCCN 2016001268 | ISBN 9780323113281 (hardcover : international edition : alk. paper) | ISBN 9780801670572 Subjects: | MESH: Tomography, X-Ray Computed | Magnetic Resonance Imaging | Whole Body Imaging Classiication: LCC RC78.7.T6 | NLM WN 206 | DDC 616.07/54—dc23 LC record available at http://lccn.loc .gov/2016001268 Executive Content Strategist: Robin Carter Senior Content Development Specialist: Ann Ruzycka Anderson Publishing Services Manager: Patricia Tannian Senior Project Manager: Cindy Thoms Design Direction: Amy Buxton Printed in China Last digit is the print number: 9

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This book is dedicated to Elizabeth E. Haaga, daughter of John and Ellen Haaga, who was born on August 19, 1972, and died December 9, 1985. Beth had a disseminated neuroblastoma, which was diagnosed in 1984. She was treated with a bone marrow transplant and died from graft-versus-host disease and infection. As her parents, we loved her dearly and cherish the memory of her early years when she was well. After the onset of her illness, we came to know that her gentle and loving nature was accompanied by a remarkably strong character. She endured her pain and suffering without bitterness and never sought to hurt those who loved her. Indeed, most incredulously, she tried to lessen our emotional pain even while enduring her physical discomforts. Many authors have marveled at the qualities of children, and although Beth’s short life and premature death have left us saddened beyond comprehension, her remarkable courage and sweetness have given us a lasting pride and respect. We remember her lovingly. The book is also dedicated to my wonderful family: my wife and soul mate, Ellen, and our children, Matthew and Stacie Haaga, Timothy and Molly Haaga, and Rebecca Haaga. Although professional successes are important and rewarding, the joy and pride of a loving family far surpass such accomplishments. All my love to my current family (and any future additions).

John R. Haaga

I am proud that my efforts as a “narrative diagnostician” have helped young physicians familiarize themselves with the challenges of modern clinical radiology. Hence, professionally, I want to dedicate this book to the wonderful mentors with whom I was honored to work over the years. A hallmark of any medical science is its continuously evolving and expanding knowledge base which, in turn, requires regular reevaluation and revitalization of established worklows. I want to thank my mentors for never tiring in reminding me of this fact and inspiring me to ind new approaches to improve patient care. Jonathan S. Lewin, MD (Emory University, Atlanta, GA), a gentleman scholar who guided me through the continuously evolving ield of applied MRI physics and the parallel research methods; as a role model he inluenced me greatly as I evolved into a scientist and mentor myself. Jeffrey L. Duerk, PhD (Case Western Reserve University, Cleveland, OH), an exceptional teacher and visionary inventor, never tiring of “translating” formulas, igures, and (magnetic) ield theories, thereby bringing together physicists and physicians in order to broaden everyone’s horizon beyond expectation. Erik K. Paulson, MD (Duke University Medical Center, Durham, NC), an outstanding diagnostician, teacher and leader who inspired me not only with his expertise and devotion to medical science and clinical practice but also through his willingness to explore unbeaten paths, thereby assembling an outstanding group of like-minded physicians and clinicians who cross-inspire each other. And inally, my life-long friend, visionary academician and exceptional mentor, Elmar M. Merkle, MD (University Hospital of Basel, Basel, Switzerland), who has been there every step of the way and without whom my career would not have been possible. When we all met initially, we all were in young stages of our careers. Over the evolving decades, our friendships formed and matured, emphasizing this most important characteristic of mentorship. Even now, meeting together with the now Executive Vice President for Health Affairs, the Dean of Biomedical Engineering, and two Chairmen of visionary and fascinating radiology departments, respectively, helpful and honest advice is always obtained, for mentorship is seen by these outstanding individuals as a lifelong responsibility. Thank you to all. I also want to dedicate this book to my parents, brother, and wife, who, without having (too much of) a choice, have been there every step of the way and always encouraged me to live a life as a Weltbürger, inding friends and mentors all across the world. I will see you at home, wherever this will be; thank you for everything.

Daniel T. Boll

SECTION EDITORS Kristine A. Blackham, MD

Raj M. Paspulati, MD

Assistant Professor Divisions of Radiology and Neurosurgery University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio

Associate Professor Department of Radiology University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio

Mauricio Castillo, MD

Prabhakar Rajiah, MD

Distinguished Professor of Radiology Chief of Neuroradiology University of North Carolina Chapel Hill, North Carolina

Associate Professor of Radiology Cardiothoracic Imaging Associate Director of Cardiac CT and MRI University of Texas Southwestern Medical Center Dallas, Texas

Thorsten R. Fleiter, MD Associate Professor Department of Diagnostic Imaging and Nuclear Medicine University of Maryland Medical Center R Adams Cowley Shock Trauma Center Baltimore, Maryland

Robert C. Gilkeson, MD Director of Cardiothoracic Imaging Professor of Radiology University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio

Claudia M. Hillenbrand, PhD Associate Member Department of Diagnostic Imaging Division of Translational Imaging Research St. Jude Children’s Research Hospital Memphis, Tennessee

Richard A. Leder, MD Associate Professor of Radiology Clinical Associate in Surgery Duke University School of Medicine Durham, North Carolina

Mark R. Robbin, MD Professor Department of Radiology Chief, Musculoskeletal Imaging University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio

Ehsan Samei, PhD, DABR, FAAPM, FSPIE Professor of Radiology, Medical Physics, Biomedical Engineering, Physics, and Electrical and Computer Engineering Director, Carl E. Ravin Advanced Imaging Laboratories Founding Chief Clinical Imaging Physics Group Duke University Medical Center Durham, North Carolina

Jeffrey L. Sunshine, MD, PhD Professor of Radiology, Neurology, Neurosurgery Vice Chairman, Department of Radiology University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Chief Medical Information Oficer, University Hospitals Cleveland, Ohio

Frank K. Wacker, MD Jeong Min Lee, MD Professor Department of Radiology Seoul National University Hospital Seoul, Korea

Suresh K. Mukherji, MD, MBA, FACR Professor and Chairman Department of Radiology Walter F. Patenge Endowed Chair Chief Medical Oficer and Director of Health Care Delivery Michigan State University Health Team East Lansing, Michigan

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Institute of Diagnostic and Interventional Radiology University School of Medicine Hannover, Germany

CONTRIBUTORS James J. Abrahams, MD

Mustafa R. Bashir, MD

Donna G. Blankenbaker, MD

Professor, Diagnostic Radiology Diagnostic Radiology Program Fellowship Director, Neuroradiology Yale University School of Medicine New Haven, Connecticut Orbit

Assistant Professor Department of Radiology Duke University Medical Center Durham, North Carolina Tissue Characterization in Liver Imaging Using Advanced MR Techniques

Professor of Radiology Department of Radiology University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Hip and Pelvis

Michael Abrahams, MD

Javier Beltran, MD, FACR

Uttam K. Bodanapally, MBBS

Department of Emergency Medicine University of Toledo Toledo, Ohio Orbit

Chairman Department of Radiology Maimonides Medical Center Brooklyn, New York Clinical Director of Musculoskeletal Radiology Radisphere National Radiology Group Beachwood, Ohio Knee

Assistant Professor Department of Diagnostic Radiology and Nuclear Medicine University of Maryland Medical Center R Adams Cowley Shock Trauma Center Baltimore, Maryland Traumatic Brain Injury

Federica Agosta, MD, PhD Neuroimaging Research Unit Institute of Experimental Neurology Division of Neuroscience San Raffaele Scientiic Institute Vita-Salute San Raffaele University Milan, Italy Neurodegenerative Disorders

Muneeb Ahmed, MD, FSIR Chief Division of Vascular and Interventional Radiology Beth Israel Deaconess Medical Center Associate Professor of Radiology Harvard Medical School Boston, Massachusetts Image-Guided Ablation of Parenchymal Organs

Stuart Bentley-Hibbert, MD, PhD Associate Professor of Radiology Department of Radiology Columbia University Medical Center New York, New York Mesentery

Professor Radiodiagnosis Tata Memorial Hospital Mumbai, India Pharynx

Associate Professor Department of Imaging Sciences University of Rochester Rochester, New York Kidney

Department of Radiology University Hospitals/Case Medical Center Cleveland, Ohio Knee Musculoskeletal Tumors

Sotirios Bisdas, MD, PhD, MSc Yong Ho Auh, MD Professor of Radiology Weill Cornell Medical College of Cornell University Attending Radiologist New York-Presbyterian Hospital New York, New York Mesentery

Romulo Baltazar, MD Attending Radiologist Imaging Subspecialists of North Jersey St. Joseph’s Regional Medical Center Paterson, New Jersey Knee

Professor of Radiology Associate Dean for Academic and Clinical Affairs Harvard Medical School Boston, Massachusetts Airway

Daniel T. Boll, MD, FSCBT Shweta Bhatt, MD

Nicholas Bhojwani, MD Supreeta Arya, MD, DMRD, DNB

Phillip M. Boiselle, MD

Neuroradiology Consultant National Hospital for Neurology and Neurosurgery Honorary Senior Lecturer University College London London, United Kingdom Professor of Radiology Department of Neuroradiology Karls Eberhard University Tübingen, Germany Adenopathy and Neck Masses

Professor of Radiology Section Chief Abdominal and Oncologic Imaging University Hospital of Basel Basel, Switzerland Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases Tissue Characterization in Liver Imaging Using Advanced Magnetic Resonance Techniques

Eliana Bonfante, MD Assistant Professor of Radiology Department of Diagnostic and Interventional Imaging University of Texas Health Science Center Houston, Texas Spinal Trauma

Jeffrey R. Brace, MD Assistant Professor of Radiology University of Minnesota Medical Center, Fairview Hennepin County Medical Center Minneapolis Veterans Affairs Medical Center Minneapolis, Minnesota Intracranial Neoplasms

Kristine A. Blackham, MD Assistant Professor Divisions of Radiology and Neurosurgery University Hospitals/Case Medical Center Case Western Reserve University Cleveland, Ohio Intracranial Neoplasms

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Contributors

Miriam A. Bredella, MD

Onofrio Catalano, MD

Jared D. Christensen, MD

Associate Professor of Radiology Harvard Medical School Department of Radiology Musculoskeletal Imaging and Interventions Massachusetts General Hospital Boston, Massachusetts Shoulder

Assistant Professor of Radiology Division of Abdominal Surgery Harvard Medical School Boston, Massachusetts Pancreas

Assistant Professor Radiology Duke University Medical Center Durham, North Carolina Mediastinal Disease

Majid Chalian, MD

Michael Coffey, MD

Radiology House Staff, PGY3 Radiology University Hospitals Case Western Reserve University Cleveland, Ohio High Resolution 3T Magnetic Resonance Neurography: Applications, Techniques, Pitfalls

Assistant Professor Radiology Case Western Reserve University School of Medicine Cleveland, Ohio Demyelinating Disease and Leukoencephalopathies

Michael K. Brooks, MD, MPH Clinical Assistant Professor of Radiology SUNY-Stony Brook Department of Radiology Division of Musculoskeletal Imaging and Intervention Winthrop University Hospital Mineola, New York Degenerative Disease

Christopher Brown, MD Research Analyst Department of Diagnostic Radiology University of Maryland Medical Center Baltimore, Maryland Coronary Arteries, Heart, and Pericardium

Ji Y. Buethe, MD Chief Resident Department of Radiology University Hospitals/Case Medical Center Cleveland, Ohio Image-Guided Drainages

John A. Carrino, MD, MPH Vice Chairman of Radiology Department of Radiology and Imaging Hospital for Special Surgery New York, New York High-Resolution 3T Magnetic Resonance Neurography: Applications, Techniques, and Pitfalls

Brian Cox, MD Ronil V. Chandra, MBBS (Hons), MMed, FRANZCR Associate Professor Neuroradiology Service Monash Imaging Monash Health Stroke and Ageing Research Centre Monash University Melbourne, Victoria, Australia Stroke

Tushar Chandra, MD Clinical Instructor Radiology Medical College of Wisconsin Milwaukee, Wisconsin Pharynx

Apeksha Chaturvedi, MD Assistant Professor Radiology University of Rochester Medical Center Rochester, New York Chest Imaging in the Pediatric Patient

Francesca Caso, MD

Avneesh Chhabra, MD

Neuroimaging Research Unit Institute of Experimental Neurology Division of Neuroscience San Raffaele Scientiic Institute Vita-Salute San Raffaele University Milan, Italy Neurodegenerative Disorders

Department of Radiology University of Texas Southwestern Medical Center Dallas, Texas High-Resolution 3T Magnetic Resonance Neurography: Applications, Techniques, and Pitfalls

Mauricio Castillo, MD

Dong-il Choi, MD

Distinguished Professor of Radiology Chief of Neuroradiology University of North Carolina Chapel Hill, North Carolina Brain Proton Magnetic Resonance Spectroscopy Cystic Lesions

Associate Professor Sungkyunkwan University School of Medicine Faculty, Department of Radiology Samsung Medical Center Seoul, Republic of Korea Biliary Tract and Gallbladder

Department of Radiology University of Texas Southwestern Medical Center Dallas, Texas High-Resolution 3T Magnetic Resonance Neurography: Applications, Techniques, and Pitfalls

Kelly L. Cox, DO Assistant Professor Radiology and Imaging Sciences Emory University Hospitals and School of Medicine Atlanta, Georgia Female Pelvis

Sheilah Curran-Melendez, MD Department of Diagnostic Radiology Allegheny General Hospital Pittsburgh, Pennsylvania Meningeal Processes

Hugh D. Curtin, MD Professor of Radiology Harvard Medical School Chief of Radiology Massachusetts Eye and Ear Boston, Massachusetts Larynx

Carlo N. De Cecco, MD, PhD Assistant Professor Department of Radiology and Radiological Sciences Division of Cardiovascular Imaging Medical University of South Carolina Charleston, South Carolina Advanced Cardiovascular CT Imaging

Contributors Alfred Delumpa, MD

Massimo Filippi, MD

Ritu R. Gill, MD, MPH

Fellow Department of Neuroradiology Baylor College of Medicine Houston, Texas Spinal Tumors

Professor Neuroimaging Research Unit Department of Neurology Division of Neuroscience Institute of Experimental Neurology San Raffaele Scientiic Institute Vita-Salute San Raffaele University Milan, Italy Neurodegenerative Disorders

Associate Radiologist Assistant Professor of Radiology Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts Disease of the Pleura, Chest Wall, and Diaphragm

David R. Di Lorenzo, MD Diagnostic Radiology University Hospitals/Case Medical Center Cleveland, Ohio Peritoneum

Thorsten R. Fleiter, MD

Professor of Radiology and Urology Department of Imaging Sciences University of Rochester Rochester, New York Kidney

Associate Professor Department of Diagnostic Imaging and Nuclear Medicine University of Maryland Medical Center R Adams Cowley Shock Trauma Center Baltimore, Maryland Traumatic Brain Injury

David Dreizin, MD

Tomás Franquet, MD

Assistant Professor Department of Diagnostic Radiology and Nuclear Medicine University of Maryand Medical Center R Adams Cowley Shock Trauma Center Baltimore, Maryland Spinal Cord Injury Traumatic Brain Injury

Chief, Section of Thoracic Imaging Radiology Hospital de Sant Pau Associate Professor of Radiology Universitat Autonoma de Barcelona Barcelona, Spain Nonneoplastic Parenchymal Lung Disease

Vikram S. Dogra, MD

Melanie B. Fukui, MD Jeremy J. Erasmus, MBBCh Professor Diagnostic Radiology University of Texas MD Anderson Cancer Center Houston, Texas Neoplastic Disease of the Lung

Maryam Etesami, MD Radiology Case Western Reserve University University Hospitals Case Medical Center Cleveland, Ohio Chest Imaging in the Pediatric Patient

Steven Falcone, MD, MBA Professor Radiology, Neurological Surgery, Ophthalmology Executive Dean for Clinical Affairs Miller School of Medicine Chief Executive Oficer University of Miami Medical Group Associate Vice President for Medical Affairs University of Miami Miami, Florida Systemic Diseases Affecting the Spine

Aurora Neuroscience Innovation Institute St. Luke’s Medical Center Milwaukee, Wisconsin Meningeal Processes

John L. Go, MD Director of Head and Neck Imaging Medical Director of the Imaging Science Center University of Southern California Keck School of Medicine Los Angeles, California Cerebral Infections and Inlammation

Joseph R. Grajo, MD Assistant Professor of Radiology University of Florida College of Medicine Gainesville, Florida Male Pelvis

Sachin K. Gujar, MBBS, MD Assistant Professor Neuroradiology Division Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore, Maryland Functional Magnetic Resonance Imaging

Junyu Guo, PhD Stephen R. Fuller, BS Department of Radiology and Radiological Sciences Division of Cardiovascular Imaging Medical University of South Carolina Charleston, South Carolina Advanced Cardiovascular CT Imaging

MR Scientist Diagnostic Imaging St. Jude Children’s Research Hospital Memphis, Tennessee Contrast-Enhanced Magnetic Resonance Imaging

Amit Gupta, MD Nicholas L. Fulton, MD Resident Radiology University Hospitals/Case Medical Center University Heights, Ohio Vasculogenesis

Fellow, Neuroradiology University Hospitals/Case Medical Center Cleveland, Ohio Demyelinating Disease and Leukoencephalopathies

Hyun Kwon Ha, MD Romyll Garcia, MD Voluntary Assistant Professor Radiology University of Miami Miami, Florida Systemic Diseases Affecting the Spine

Amilcare Gentili, MD Professor Radiology University of California–San Diego San Diego, California Musculoskeletal Tumors http://pdf-radiology.com/

Professor of Radiology University of Ulsan College of Medicine Professor and Chief of Gastrointestinal Section Department of Radiology Asan Medical Center Seoul, Republic of Korea Gastrointestinal Tract

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Contributors

John R. Haaga, MD, FACR, FSIR, FSCBT, FSRS Gold Medalist AARS and SCBTMRI Professor of Radiology Case Western Reserve University School of Medicine Emeritus Chairman and Professor of Radiology University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio Image-Guided Aspirations and Biopsies Imaging Principles in Computed Tomography Peritoneum Vasculogenesis

Ellen Hoeffner, MD

Stephen A. Kieffer, MD

Professor of Radiology University of Michigan Ann Arbor, Michigan Pharynx Temporal Bone

Professor of Radiology (Neuroradiology) University of Minnesota Medical School Attending Radiologist University of Minnesota Medical Center, Fairview Hemepin County Medical Center Minneapolis Veterans Affairs Medical Center Minneapolis, Minnesota Intracranial Neoplasms

Alena Horská, PhD Assistant Professor Russell H. Morgan Department of Radiology and Radiological Science Division of Neuroradiology Johns Hopkins University School of Medicine Baltimore, Maryland Brain Proton Magnetic Resonance Spectroscopy

Timothy L. Haaga, MD Clinical Assistant Professor Radiology University Hospitals/Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio Image-Guided Aspirations and Biopsies

Mukesh G. Harisinghani, MD Professor of Radiology Harvard Medical School Boston, Massachusetts Male Pelvis

Tobias Heye, MD Department of Radiology University Hospital of Basel Basel, Switzerland Tissue Characterization in Liver Imaging Using Advanced Magnetic Resonance Techniques

Claudia M. Hillenbrand, PhD Associate Member Department of Diagnostic Imaging Division of Translational Imaging Research St. Jude Children’s Research Hospital Adjunct Associate Professor Department of Biomedical Engineering University of Memphis Memphis, Tennessee Magnetic Resonance Imaging in the Pediatric Patient

Lisa M. Ho, MD Associate Professor of Radiology Department of Radiology Duke University Medical Center Durham, North Carolina Adrenal Glands

David W. Jordan, PhD Senior Medical Physicist, Radiology University Hospitals/Case Medical Center Assistant Professor, Radiology Case Western Reserve University Cleveland, Ohio Imaging Principles in Computed Tomography Imaging Principles in Magnetic Resonance Imaging

Ah Young Kim, PhD Associate Professor of Radiology University of Ulsan College of Medicine Associate Professor of Radiology Division of Abdominal Radiology Asan Medical Center Seoul, Republic of Korea Gastrointestinal Tract

Jung Hoon Kim, MD Assistant Professor Medicine-Geriatrics Baylor College of Medicine Houston, Texas Mesentery

Kyoung Won Kim, MD, PhD Varsha Joshi, DNB, DMRD Senior Consultant Division of CT and MRI Vijaya Diagnostic Centres Hyderabad, India Visiting Consultant Tata Medical Center Kolkata, India Paranasal Sinuses

Sue C. Kaste, DO Full Member Department of Diagnostic Imaging Department of Oncology St. Jude Children’s Research Hospital Full Professor, Radiology University of Tennessee School of Health Sciences Memphis, Tennessee Magnetic Resonance Imaging in the Pediatric Patient

Simon Rupe Khangure, MD, MBBS, BMdSc, FRANZCR Neuroradiology Service Monash Imaging Monash Health Melbourne, Victoria, Australia Stroke

Assistant Professor of Radiology University of Ulsan College of Medicine Faculty Member, Department of Radiology Asan Medical Center Seoul, Republic of Korea Biliary Tract and Gallbladder

Paul E. Kim, MD University of Southern California Keck School of Medicine Los Angeles, California Cerebral Infections and Inlammation

Seth Kligerman, MD Associate Professor of Radiology Diagnostic Radiology and Nuclear Medicine University of Maryland Baltimore, Maryland Coronary Arteries, Heart, and Pericardium

Satoshi Kobayashi, MD, PhD Professor Quantum Medical Technology Kanazawa University Graduate School of Medical Science Kanazawa, Japan Liver: Focal Hepatic Mass Lesions

Christos Kosmas, MD Assistant Professor of Radiology Division of Musculoskeletal Imaging University Hospitals/Case Medical Center Case Western Reserve University Cleveland, Ohio Foot and Ankle

http://pdf-radiology.com/

Contributors

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Gerdien Kramer, MD

Jae Hoon Lim, MD

Osamu Matsui, MD, PhD

Department of Thoracic Imaging Hopital Calmette Universite Lille Nord de France Lille, France Coronary Arteries, Heart, and Pericardium

Department of Radiology Myongji Hospital Goyang, Republic of Korea Biliary Tract and Gallbladder

Professor Emeritus Radiology Kanazawa University Graduate School of Medical Science Kanazawa, Japan Liver: Focal Hepatic Mass Lesions

Chia-Shang J. Liu, MD, PhD Timo Krings, MD, PhD, FRCPC The David Braley and Nancy Gordon Chair in Interventional Neuroradiology Chief of Diagnostic and Interventional Neuroradiology Toronto Western Hospital and University Health Network Professor of Radiology and Surgery University of Toronto Toronto, Ontario, Canada Vascular Lesions

Assistant Professor Radiology University of Southern California Keck School of Medicine Los Angeles, California Cerebral Infections and Inlammation

Minh Lu, MD Radiology University of Maryland Baltimore, Maryland Coronary Arteries, Heart, and Pericardium

Lester Kwock, PhD Professor of Radiology University of North Carolina School of Medicine Chapel Hill, North Carolina Brain Proton Magnetic Resonance Spectroscopy

Kenneth Lury, MD Assistant Professor (Retired) Radiology University of North Carolina Chapel Hill, North Carolina Noninfectious Inlammatory Diseases Affecting the Spinal Cord

Theodore C. Larson III, MD Director of Neurointervention Centura Neurosciences St. Anthony Hospital Lakewood, Colorado Cerebral Aneurysms and Cerebrovascular Malformations

Calvin T. Ma, MD

Leslie K. Lee, MD

Henry Ma, MBBS, FRACP

Instructor in Radiology Harvard Medical School Boston, Massachusetts Male Pelvis

Associate Professor Stroke Unit, Monash Health Stroke and Ageing Research Centre Monash University Melbourne, Victoria, Australia Stroke

Seung Soo Lee, MD Assistant Professor of Radiology University of Ulsan College of Medicine Seoul, Republic of Korea Gastrointestinal Tract

Young-Jun Lee, MD, PhD Associate Professor, Radiology Hanyang University Hospital Seoul, South Korea Spinal Vascular Diseases

Alexander Lerner, MD Assistant Professor of Clinical Radiology Radiology University of Southern California Keck School of Medicine Los Angeles, California Cerebral Infections and Inlammation

Staff Radiologist Sutter Imaging Sutter Health Sacramento Sierra Region Sacramento, California Knee

Bahar Mansoori, MD Department of Radiology University Hospitals Case Western Reserve University Cleveland, Ohio High-Resolution 3T Magnetic Resonance Neurography: Applications, Techniques, and Pitfalls

Joseph P. Mazzie, DO Clinical Assistant Professor of Radiology SUNY-Stony Brook Department of Radiology Division of Musculoskeletal Imaging and Intervention Winthrop University Hospital Mineola, New York Degenerative Disease

H. Page McAdams, MD Professor of Radiology Radiology Duke University Medical Center Durham, North Carolina Mediastinal Disease

Indu Rekha Meesa, MD, MS Neuroradiology and Pediatric Radiologist Summit Radiology Fort Wayne, Indiana Neuroradiology and Pediatric Radiology Fellow Department of Radiology University of Michigan Ann Arbor, Michigan Imaging of the Head and Neck in the Pediatric Patient

Carolyn Cidis Meltzer, MD William P. Timmie Professor and Chair Department of Radiology and Imaging Sciences Associate Dean for Research Emory University School of Medicine Atlanta, Georgia Meningeal Processes

Elmar M. Merkle, MD Department of Radiology University Hospital of Basel Basel, Switzerland Tissue Characterization in Liver Imaging Using Advanced MR Techniques

Daniel Mascarenhas, BS

Achille Mileto, MD

Department of Diagnostic Radiology and Nuclear Medicine University of Maryland Medical Center R Adams Cowley Shock Trauma Center Baltimore, Maryland Spinal Cord Injury Traumatic Brain Injury

Department of Radiology Duke University School of Medicine Durham, North Carolina Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases

http://pdf-radiology.com/

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Contributors

Suyash Mohan, MD, PDCC

John P. Nazarian, MD

Manuel Patino, MD

Assistant Professor of Radiology Radiology, Neuroradiology Division University of Pennsylvania Philadelphia, Pennsylvania Pharynx Temporal Bone

Resident, Radiology University Hospitals/Case Medical Center Cleveland, Ohio Demyelinating Disease and Leukoencephalopathies

Postdoctoral Fellow Division of Abdominal Imaging Massachusetts General Hospital Boston, Massachusetts Pancreas

Manal Nicolas-Jilwan, MD

Thanh Phan, MD, MBBS, FRACP

Radiology University of Virginia Health System Charlottesville, Virginia Congenital Abnormalities

Professor Stroke Unit, Monash Health Stroke and Ageing Research Centre Monash University Melbourne, Australia Stroke

Jesse Montagnese, MD Assistant Professor Radiology University of Pittsburgh Pittsburgh, Pennsylvania Intracranial Neoplasms

Sameh K. Morcos, FRCS, FFRRCSI, FRCR Professor of Diagnostic Imaging University of Shefield Consultant Radiologist Northern General Hospital Shefield, United Kingdom Contrast Nephropathy and Its Management

Sherif G. Nour, MD, FRCR Director, Interventional MRI Program Associate Professor of Radiology and Imaging Sciences Department of Radiology and Imaging Sciences Emory University Hospitals and School of Medicine Atlanta, Georgia Female Pelvis MRI-Guided Interventions

Fanny E. Morón, MD Associate Professor of Diagnostic Radiology Baylor College of Medicine Houston, Texas Spinal Neoplasms

Suresh Mukherji, MD, MBA, FACR Professor and Chairman Department of Radiology Walter F. Patenge Endowed Chair Chief, Medical Oficer and Director of Health Care Delivery Michigan State University Health Team East Lansing, Michigan Imaging of the Head and Neck in the Pediatric Patient

A. Orlando Ortiz, MD, MBA, FACR Clinical Professor of Radiology SUNY-Stony Brook Chairman, Department of Radiology Winthrop University Hospital Mineola, New York Degenerative Disease

Theeraphol Panyaping, MD Diagnostic Neuroradiology Division Department of Radiology Ramathibodi Hospital Mahidol University Ratchathewi, Bangkok, Thailand Spinal Infection

Dean A. Nakamoto, MD

Seong Ho Park, MD

Section Chief, Abdominal Imaging Radiology University Hospitals/Case Medical Center Cleveland, Ohio Computed Tomography—Guided Drainage Spleen

Associate Professor of Radiology University of Ulsan College of Medicine Asan Medical Center Seoul, Republic of Korea Gastrointestinal Tract

Raj M. Paspulati, MD Sadhna B. Nandwana, MD Assistant Professor Department of Radiology and Imaging Sciences Emory University Hospitals and School of Medicine Atlanta, Georgia Female Pelvis

Associate Professor Radiology University Hospitals/Case Medical Center Case Western Reserve University Cleveland, Ohio Liver Transplantation Rectum

http://pdf-radiology.com/

Jay J. Pillai, MD Director of Functional MRI Associate Professor Neuroradiology Division Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore, Maryland Brain Proton Magnetic Resonance Spectroscopy Functional Magnetic Resonance Imaging

Colin S. Poon, MD, PhD, FRCPC Assistant Clinical Professor Department of Diagnostic Radiology Yale University School of Medicine New Haven, Connecticut Staff Radiologist Orillia Soldiers’ Memorial Hospital Orillia, Ontario, Canada Orbit

Andrea Prochowski, MD Postdoctoral Fellow Division of Abdominal Imaging Massachusetts General Hospital Boston, Massachusetts Pancreas

Anandh Rajamohan, MD Assistant Professor Radiology University of Southern California Keck School of Medicine Los Angeles, California Cerebral Infections and Inlammation

Prabhakar Rajiah, MD Associate Professor of Radiology Cardiothoracic Imaging Associate Director of Cardiac CT and MRI University of Texas Southwestern Medical Center Dallas, Texas Chest Imaging in the Pediatric Patient

Contributors Parvati Ramchandani, MD

Nisha Sainani, MD

Eric Schrauben, PhD

Professor of Radiology and Surgery, Section Chief GU Radiology Department of Radiology Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Retroperitoneum

Assistant Professor of Radiology Harvard Medical School Staff Radiologist Abdominal Imaging and Intervention Brigham and Women’s Hospital Boston, Massachusetts Pancreas

Medical Physics University of Wisconsin–Madison Madison, Wisconsin Imaging Principles in Magnetic Resonance Angiography

Wilburn E. Reddick, PhD Member Faculty Diagnostic Imaging St. Jude Children’s Research Hospital, Memphis, Tennessee Contrast-Enhanced Magnetic Resonance Imaging

Matthias Renker, MD Visiting Scholar Department of Radiology and Radiological Services Division of Cardiovascular Imaging Medical University of South Carolina Charleston, South Carolina Resident, Department of Medicine I, Cardiology/Angiology University Hospital Giessen Giessen, Germany Advanced Cardiovascular CT Imaging

Roy Riascos, MD, DABR Associate Professor Chief of Neuroradiology Department of Diagnostic and Interventional Imaging University of Texas Health Science Center at Houston Houston, Texas Spinal Trauma

Mark R. Robbin, MD Professor Department of Radiology Chief, Division of Musculoskeletal Imaging University Hospitals/Case Medical Center Case Western Reserve School of Medicine Cleveland, Ohio Musculoskeletal Tumors

Haris I. Sair, MD Assistant Professor Neuroradiology Division Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore, Maryland Functional Magnetic Resonance Imaging

Dilan Samarawickrama, MD Neuroradiology Fellow Radiology University of Michigan Ann Arbor, Michigan Temporal Bone

Rima Sansi, DNB Clinical Associate Department of Radiology Sir H.N. Reliance Foundation Hospital and Research Centre Prarthana Samaj, Girgaum, Mumbai, India Paranasal Sinuses

Asha Sarma, MD Resident Radiology Brigham and Women’s Hospital Boston, Massachusetts Disease of the Pleura, Chest Wall, and Diaphragm

Piyush Saxena, DNB, MBBS Consultant Radiologist and Chief of MRI Radiodiagnosis Vishesh Hospital and Diagnostics Indore, Madhya Pradesh, India Paranasal Sinuses

Santiago E. Rossi, MD Centro de Diagnostico Dr Enrique Rossi Buenos Aires, Argentina Neoplastic Disease of the Lung

Dushyant Sahani, MD Associate Professor of Radiology Harvard Medical School Director of Computed Tomography Massachusetts General Hospital Division of Abdominal Imaging and Intervention Boston, Massachusetts Pancreas

Ken L. Schreibman, MD, PhD Professor of Radiology Division of Musculoskeletal Imaging University of Wisconsin–Madison University of Wisconsin Hospitals and Clinics Madison, Wisconsin Foot and Ankle

Danielle M. Seaman, MD Staff Radiologist Radiology Durham Veterans Affairs Medical Center Durham, North Carolina Mediastinal Disease

Nicole Seiberlich, PhD Assistant Professor Biomedical Engineering Case Western Reserve University Cleveland, Ohio Imaging Principles in Magnetic Resonance Imaging

Saugata Sen, MD Senior Consultant Radiology and Nuclear Medicine Tata Medical Center Kolkata, West Bengal, India Paranasal Sinuses

Rickin Shah, MD Department of Radiology University of Michigan Health System Ann Arbor, Michigan Temporal Bone

Steven Shankman, MD Vice-Chairman, Department of Radiology Maimonides Medical Center Brooklyn, New York Knee

U. Joseph Schoepf, MD Professor Department of Radiology and Radiological Sciences Division of Cardiovascular Imaging Director, CT Research and Development Medical University of South Carolina Charleston, South Carolina Advanced Cardiovascular CT Imaging

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xv

Kenneth Sheah, MBBS FRCR MMed (Diagnostic Radiology) Consultant Radiologist Lifescan Imaging Pte Ltd Singapore Shoulder

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Contributors

Haojun Shi, MD

Mark Patrick Supanich, PhD

Charles S. White, MD

Assistant Professor of Radiology Huazhong University of Science and Technology Department of Radiology Union Hospital Wuhan, Hubei Province, China Normal Anatomy

Associate Professor Diagnostic Radiology and Nuclear Medicine Rush University Medical Center Chicago, Illinois Computed Tomography Imaging Operation

Professor of Radiology and Medicine University of Maryland Medical Center Baltimore, Maryland Coronary Arteries, Heart, and Pericardium

George Shih, MD Adjunct Assistant Professor of Radiology Columbia University College of Physicians and Surgeons Associate Attending Radiologist New York-Presbyterian Hospital Associate Professor of Clinical Radiology Weill Cornell Medical College New York, New York Mesentery

Julian Lukas Wichmann, MD Katarina Surlan-Popovic, MD, PhD Associate Professor of Radiology Clinical Institute of Radiology University Medical Center Ljubljana Ljubljana, Slovenia Adenopathy and Neck Masses

Janio Szklaruk, PhD, MD Professor of Diagnostic Radiology University of Texas MD Anderson Cancer Center Houston, Texas Spinal Tumors

Mark S. Shiroishi, MD

Visiting Instructor Department of Radiology and Radiological Sciences Division of Cardiovascular Imaging Medical University of South Carolina Charleston, South Carolina Resident Department of Diagnostic and Interventional Radiology University Hospital Frankfurt Frankfurt, Germany Advanced Cardiovascular CT Imaging

Oliver Wieben, PhD

Assistant Professor Radiology University of Southern California Keck School of Medicine Los Angeles, California Cerebral Infections and Inlammation

Gustavo A. Tedesqui, MD Research Fellow Neuroradiology University of North Carolina Chapel Hill, North Carolina Cystic Lesions

Associate Professor Medical Physics and Radiology University of Wisconsin–Madison Madison, Wisconsin Imaging Principles in Magnetic Resonance Angiography

Stephanie Soriano, MD

Aaryani Tipirneni-Sajja, MS

Leo Wolansky, MD

Radiology University Hospitals/Case Medical Center Cleveland, Ohio Spleen

Research Assistant Division of Translational Imaging Research Department of Diagnostic Imaging St. Jude Children’s Research Hospital Research Assistant Department of Biomedical Engineering University of Memphis Memphis, Tennessee Magnetic Resonance Imaging in the Pediatric Patient

Professor, Radiology Case Western Reserve University School of Medicine Cleveland, Ohio Demyelinating Disease and Leukoencephalopathies

Cathy Soufan, MD Neuroradiology Service Monash Imaging Monash Health Melbourne, Victoria, Australia Stroke

Drew A. Torigian, MD, MA Jason W. Stephenson, MD Assistant Professor of Radiology Department of Radiology University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Hip and Pelvis

Stephen L. Stuckey, MBBS, MD, MMed, FRANZCR, FAANMS, PGDA Director Monash Imaging Monash Health Department of Imaging Monash University Melbourne, Victoria, Australia Stroke

Associate Professor of Radiology Department of Radiology Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Retroperitoneum

Erik M. Velez, MD Department of Radiology Beth Israel Deaconess Medical Center Boston, Massachusetts Image-Guided Ablation of Parenchymal Organs

Thomas J. Vogl, MD Professor of Radiology Chair Department of Diagnostic and Interventional Radiology University Hospital Frankfurt Frankfurt, Germany Adenopathy and Neck Masses

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Hanping Wu, MD Resident Department of Radiology University Hospitals/Case Medical Center Cleveland, Ohio Image-Guided Aspirations and Biopsies Normal Anatomy

Haibo Xu, MD Chairman Department of Radiology Zhongnan Hospital of Wuhan University Wuhan, Hubei Province, China Normal Anatomy

Chi-Shing Zee, MD Professor of Radiology and Neurosurgery Department of Radiology Keck Hospital of University of Southern California Los Angeles, California Cerebral Infections and Inlammation

P R E FA C E This sixth edition of CT and MRI of the Whole Body represents a monumental accomplishment for Elsevier and our many contributing authors, editors, and section editors who have contributed past and present. The authors of the current chapters are due many, many kudos because of the changes that have occurred in healthcare with the emphasis on “productivity” and RVUs. Institutions have reduced physician support in the form of secretaries, assistants, etc., which makes it very dificult for academic physicians to contribute to projects such as this book. THANK YOU, THANK YOU! Being senior editor of this book has been a remarkable honor for me because it enabled me to collaborate with many radiologists and physicists. Everyone who has been involved for the past 40 years can take great pride in this book because it has formed the foundation for educating thousands of fellow radiologists in the United States and around the world. Over the years, radiologists from all over the world have expressed their gratitude for having this book available as a reference. As I relect back, I become nostalgic just thinking about how exciting radiology has been for the past 40 years. So many innovations and advances have been made. Of the contributions I have made, I am the most proud of developing CT interventions such as biopsies, abscess drainages, nerve blocks, the Topogram/Scoutview, and radiation dose reduction. It is very lattering that the Smithsonian Institution asked for and accepted for curation several personal artifacts related to these innovations. Over the years I have met many pioneers in the ield of imaging, but my two favorites were Sven Seldinger, MD (Fig. 1), and Paul Lauterbur, PhD (Fig. 2), as pictured below. Dr. Seldinger was a very dynamic person who developed the Seldinger Technique for angiography.

Unfortunately, he didn’t receive the recognition he deserved until late in his career. Few know that he did not receive an academic appointment until we awarded him with one at Case Western Reserve University. Paul Lauterbur was the genius who received the Nobel Prize for MRI. Strangely enough, he and I lived in the same small town, Troy, Ohio, for a number of years. His sense of humor as well as his science was of Nobel quality. I have taken the editor’s prerogative of referencing and publishing my own innovations in this book. My last innovation, which I am conident will improve the diagnosis and treatment of cancer, is the ALPHA concept, which is discussed in Chapter 70. The concept has been published in the journals Surgery and the American Journal of Roentgenology (AJR). We have just inished the experimental proof of ALPHA, which includes standard laboratory tests, but also the latest RNA sequencing tests. We will be submitting it for publication soon. This concept explains how aerobic metabolism has been overemphasized and that glycolysis is more important for the development and treatment of cancer. I hope and believe that we will be able to diagnose and cure many more cancers with this knowledge. Readers are encouraged to search the literature for future publications by my protégés who are continuing this work. There are numerous young physicians working on this concept who have accomplished much to date. I would like to acknowledge a number of young investigators, Hooman Yarmohammadi, MD; Luke Wilkins, MD; Steven Dreyer, MD; Dan Patel, MD; Nicholas Fulton, and Ji Buethe, for their hard work and commitment to continue work on this ALPHA concept.

FIG 1 Sven Seldinger (right) and John R. Haaga.

FIG 2 Paul Lauterbur (right) and John R. Haaga.

John R. Haaga

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P R E FAC E TO T H E F I R S T E D I T I O N Since the introduction of computed tomography (CT) in 1974, there has been a remarkable revolution in the medical treatment of patients. The clinical use of CT has had a broad positive impact on patient management. Literally thousands of patients have been saved or their quality of life improved as a result of the expeditious and accurate diagnosis provided by CT. This improvement in diagnosis and management has occurred in all medical subspecialties, including neurological, pulmonary, cardiac, gastrointestinal, genitourinary, and neuromuscular medicine. Aside from the imaging advantages provided, the role of CT in planning and performing interventional procedures is now recognized. It is the most accurate method for guiding procedures to obtain cytological, histological, or bacteriological specimens and for performing a variety of therapeutic procedures. The evolution and reinement of CT equipment have been as remarkable as the development of patient diagnosis. When we wrote our irst book on CT, the scanning unit used was a 2-minute translaterotate system. At the time of our second book the 18-second translaterotate scanning unit was in general use. Currently standard units in radiological practice are third and fourth generation scanners with scan times of less than 5 seconds. All modern systems are more reliable than the earlier generations of equipment. The contrast and spatial resolution of these systems are in the range of 0.5% and less than 1 mm, respectively. The sophistication of the computer programs that aid in the diagnosis is also remarkable. There are now programs for three-dimensional reconstructions, quantitation of blood low, determination of organ volume, longitudinal scans (Scoutview, Deltaview, Synerview, and Topogram), and even triangulation programs for performing percutaneous biopsy procedures. CT units are now being installed in virtually every hospital of more than 200 beds throughout the United States. Most radiologists using these units are generalists who scan all portions of the anatomy. Because of the dissemination of this equipment and its use in general diagnosis, there exists a signiicant need for a general and complete textbook to cover all aspects of CT scanning. Our book is intended to partially supplement the knowledge of this group of physicians. We have attempted to completely and succinctly cover all portions of CT scanning to provide a complete general reference text. In planning the book, we chose to include the contributions of a large number of talented academicians with expertise different from and more complete than our own in their selected areas. By including contributors

from outside our own department, we have been able to produce an in-depth textbook that combines the academic strengths of numerous individuals and departments. The book is divided into chapters according to the organ systems, except for some special chapters on abscesses and interventional procedures. In each of the chapters the authors have organized the material into broad categories, such as congenital, benign, or neoplastic disease. Each author has tried to cover the major disease processes in each of the general categories in which CT diagnosis is applicable. Speciic technical details, including the method of scanning, contrast material, collimation, and slice thickness, are covered in each chapter. The interventional chapter extensively covers the various biopsy and therapeutic procedures in all the organ systems. Finally, the last chapter presents an up-to-the-minute coverage of current and recent developments in the CT literature and also provides extensive information about nuclear magnetic resonance (NMR) imaging. At this time we have had moderate experience with the NMR superconducting magnetic device produced by the Technicare Corporation and have formulated some initial opinions as to its role relative to CT and other imaging modalities. A concise discussion of the physics of NMR and a current clinical status report of the new modality are provided. We would like to thank all those people who have worked so diligently and faithfully for the preparation of this book. First, we are very grateful to our many contributors. For photography work, we are deeply indebted to Mr. Joseph P. Molter. For secretarial and organizational skills, we are indebted especially to Mrs. Mary Ann Reid and Mrs. Rayna Lipscomb. The editorial skills of Ms. B. Hami were invaluable in preparing the manuscript. Our extremely competent technical staff included Mr. Joseph Agee, Ms. Ginger Haddad, Mrs. E. Martinelle, Mr. Mark Clampett, Mrs. Mary Kralik, and numerous others. Finally, we are, of course, very appreciative of the support, patience, and encouragement of our wonderful families. In the Haaga family this includes Ellen, Elizabeth, Matthew, and Timothy, who provided the positive motivation and support for this book. Warm gratitude for unswerving support is also due to Rose, Sue, Lisa, Chris, Katie, Mary, and John Alidi.

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John R. Haaga Ralph J. Alfidi

F O R E WO R D I am honored and pleased to write the foreword for the 40th anniversary edition of CT and MRI of the Whole Body, a textbook of radiology edited by John Haaga, MD. The esteemed Dr. Haaga has been its editor since its irst edition in 1976. Professor Haaga has received a Gold Medal from the American Roentgen Ray Society (ARRS), which is the society’s highest honor for distinguished service to radiology. He received this award for his contributions in leadership, teaching, and research, work that he continues to this day. His major innovations include CT-guided interventions that guide biopsies and treatments for abscess, nerve blocks, and cancer. Artifacts from his early work are archived at the Smithsonian Institution. At the age of 36, Dr. Haaga became a tenured professor in the Department of Radiology at Case Western Reserve University School of Medicine and University Hospitals of Cleveland. He later served for 14 years as department chairman at that institution. He has mentored and taught many hundreds of residents, fellows, and junior faculty members, many of whom have advanced to become distinguished names in their own ields. I am one such beneiciary, having had the fortune of being mentored and guided by John in my early years in radiology. His values and wisdom have allowed me to progress in the ield of radiology. I have been inspired to write many books, such as Genitourinary Radiology: Kidney, Bladder and Urethra, The Pathologic Basis, published by Springer. I also became Editor-inChief of the Journal of Clinical Imaging Science, published by Wolters Kluwer. John is bigger than a ilm celebrity in India, which I witnessed irsthand when I had the opportunity to accompany him. Everywhere he lectured in India the venue was at capacity. He was literally mobbed by radiology residents wanting to take pictures with him. This book is considered the bible of radiology in India. Every aspiring radiology resident, as well as established faculty, reads this book. I am sure the story is no different in other countries. CT and MRI of the Whole Body is the largest selling radiology textbook in the world and has been translated into Spanish, Portuguese, and Persian. More than 25,000 copies have been sold in the world. I have been an integral part of this book for the past many years,

as I have contributed a complete chapter on Imaging of the Kidney and have been Associate Editor for Genito-Urinary Radiology for its ifth edition. Dr. Haaga, a world renowned radiologist, anchors this book. He has assembled an impressive team of coauthors who are experts in various subspecialties of radiology. The book is divided into four parts: PART I—Principles of Computed Tomography and Magnetic Resonance Imaging, which is further subdivided into sections on Computed Tomography and Magnetic Resonance Imaging; PART II—CT and MR Imaging of the Whole Body, which has seven sections: Neuroradiological Imaging of the Brain and Meninges, Neuroradiological Imaging of the Head and Neck, Neuroradiological Imaging of the Spine, Imaging of the Chest, Imaging of the Abdominal and Pelvic Organs, Imaging of the Cardiovascular System, and Imaging of the Musculoskeletal System; PART III—Image-Guided Procedures; and PART IV—Leading Edge Imaging Concepts. The sixth edition of Haaga’s CT and MRI of the Whole Body is a welcome addition. The book is well organized, the chapters are uniformly structured, and each section is richly illustrated. The quality of the paper, printing, illustrations, and igures is excellent. There is ample use of line drawings to explain dificult concepts. The sixth edition of Haaga’s CT and MRI of the Whole Body is a welcome addition. I am not aware of any other radiology book in the market that is as complete and uniquely illustrated. The cost is reasonable considering the number of illustrations and the quality of work. This book meets the needs of its intended audience. The current edition is completely up to date in the ield of diagnostic radiology. It is a must have for radiology residents, radiology faculty, radiology libraries, and serious academic radiologists.

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Vikram S. Dogra, MD, FSAR, FESUR, FAIUM, FSRU Professor of Radiology, Urology & Biomedical Engineering Associate Chair of Education and Research Department of Radiology University of Rochester Rochester, New York

F O R E WO R D Very rarely does a textbook fulill the promise of being both comprehensive and readable. CT and MRI of the Whole Body, edited by Drs. John Haaga and Daniel Boll, not only fulills that promise, but has continued a legacy of success that has been sustained over multiple editions. It is an honor to have the opportunity to write this foreword. Having trained under the expert eye of Dr. John Haaga, I studied the earliest editions of this book, providing my introduction into the intricacies of cross-sectional imaging. I then had the privilege of watching this true pioneer of CT and MRI take his personal experience and use it to create a resource that has evolved as the ield has matured over the past four decades. The current edition of this text covers the wide breadth of CT and MRI anatomically, and the editors have enlisted experts in neuroradiology, head and neck imaging, abdominal imaging,

thoracic imaging, musculoskeletal radiology, physics, and a long list of other subspecialties in our ield to create a textbook that is as deep as it is broad. With the addition of the energy, talent, and creativity that Dr. Daniel Boll brings to this edition, the result is truly remarkable. I have no doubt that you will agree as you dig into this text, and learn from the combined wisdom of a team of true expert authors, as guided by the steady hands of Drs. Haaga and Boll. Enjoy!

Jonathan S. Lewin, MD, FACR Executive Vice President for Health Affairs, Emory University Executive Director, Woodruff Health Sciences Center President, CEO, and Chairman of the Board, Emory Healthcare Atlanta, Georgia

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1 Imaging Principles in Computed Tomography David W. Jordan and John R. Haaga

Computed tomography (CT) has grown quickly from an innovative specialized tool to a mainstay of medicine in every healthcare setting. Hospitals, outpatient clinics, and physician ofices ind CT to be an essential tool for patient diagnosis and management. Every year brings new advances in CT technology and applications. This chapter is dedicated to the basic principles and physics of CT operation. The practicing radiologist who can evaluate new technology with a good understanding of these principles will be successful in choosing the best tools for his or her practice and in getting the greatest beneit from them.

THE CT IMAGE Radiography reduces a three-dimensional (3D) body part to a twodimensional (2D) image with limited contrast, because structures that lie on top of one another are projected onto a single image. The contrast can be improved by using exogenous agents to enhance certain structures or by taking extra projections from different angles to separate the structures in the image plane, but there are limits to how well this can work. The advantage of CT is the improvement in image contrast that comes from using a 2D image to show an almost-2D section of the patient without the effect of overlapping structures. The CT image is a cross-sectional view of the patient rather than an x-ray shadow of the beam passing through the body part (Fig. 1-1). An x-ray beam is used to collect information about the tissues, but the image is not an ordinary projection view from the perspective of the x-ray tube looking toward the ilm or detector. The image is a crosssectional map of the x-ray attenuation of different tissues within the patient. The typical CT scan generates a transaxial image oriented in the anatomic plane of the transverse dimension of the anatomy. Reconstruction of the inal image can be reformatted to provide sagittal or coronal images; these are viewed from the same perspective as a digital radiograph, but they show thin slices of tissue rather than superimposed tissues and structures. The pixel values show how strongly the tissue attenuates the scanner’s x-ray beam compared to the attenuation of the same x-ray beam by water. The CT image is produced by the process of reconstruction: digitally combining information from x-ray projections through the patient from many different angles to produce the cross-sectional image. Because the image is digital, it is made up of a group of pixels (shortened from “picture elements”). Each pixel has a grayscale value that is displayed to the viewer. The image is 2D, but it represents a 3D volume of tissue with a inite thickness (usually a very small thickness compared to the ield-of-view (FOV) size [≈2-5 mm]). Each pixel is the projection, or 2D representation, of the x-ray attenuation of a voxel (shortened from “volume element”) of physical tissue. The size of the pixels and the thickness of the voxels relate to some important image quality features, such as detail, noise, contrast, accuracy of the attenu-

ation measurement (CT number value), and artifacts. These will be discussed in more detail as they relate to the processes of acquiring and reconstructing CT data.

CT ACQUISITION OVERVIEW The basic process of collecting data in CT is illustrated in Figure 1-2. In a CT of a single section of tissue using a single detector, the x-ray beam is collimated to the desired image thickness. The detector array has a number of individual detector elements that each record the intensity of the beam passing through the tissue along the path from the x-ray tube to the element. The system captures a simple projection x-ray through the patient, consisting of a thin strip or row of pixels. It can be thought of as a one-dimensional (1D) radiograph. The scanner then rotates the source and detector to capture additional 1D “strip x-rays” through the same section of the patient, viewed from a number of angles. Each strip radiograph (projection) is stored in the computer memory for later reconstruction. In multislice CT (Fig. 1-3) this operation is performed simultaneously for many arrays of detectors stacked side by side along the z-axis (long axis) of the patient. The x-ray beam collimators can be opened so that a wider section of the patient is irradiated, and each row of detectors can measure a separate transmission signal for the tissue section that lies between the detector row and the tube. The width of tissue that is sampled by each detector row is determined by the physical width of the detector elements along the z-axis. CT images and individual rotations of the scanner gantry are often called slices because a single data acquisition and reconstruction produces an x-ray map of a thin section of the patient’s body. The tissue displayed in the image represents the same tissue as if a thin slice or section of the patient’s body were cut in a plane perpendicular to the long axis (superior-inferior) of the patient’s body and ixed for viewing. Early CT scanners collimated the width of the x-ray beam to the width of a slice (e.g., 5 mm), irradiated one slice at a time, and collected data for transmission through one slice at a time. Multislice scanners use a wider beam to cover more tissue with each pass of the tube, and the detectors contain arrays that are arranged to collect data for multiple individual adjacent slices at the same time. The detector element(s) for each slice store data separately and represent different physical sections of tissue. The term slice can be confusing because in common use it can refer to several different things. When a CT scanner is called a “16-slice” model, it usually means that the scanner can acquire up to 16 individual detector data sets at one time. It is more precise to call this a 16–detector row CT scanner. The individual data elements acquired should be referred to as acquired images or acquired projection data. In a multidetector-row scanner, the data are often acquired in thicknesses of 0.5 to 0.7 mm and reconstructed in image thicknesses of 3 to 5 mm.

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4

PART I

Principles of Computed Tomography and Magnetic Resonance Imaging Y

XRT

Z X

FIG 1-1 A CT image represents a cross section of the imaged subject rather than the x-ray shadow of the anatomy, as in a conventional radiograph. a

b

c

d

FIG 1-3 In multislice CT, several independent detectors arranged side by side sample data from unique locations within the x-ray beam.

l (x-rays/cm2)

l0 l l0 L l = l0e −µL

L (cm)

FIG 1-4 Exponential attenuation of x-ray beam intensity in an absorber, FIG 1-2 A simple CT scan produces a one-dimensional strip radiograph

such as tissue.

for each projection through the patient.

The images that are presented to the operator or physician for viewing should be called reconstructed images, although many people continue to refer to these as slices.

Linear Attenuation and Projections The fundamental x-ray physics of CT are the same as those for radiography. A source of ionizing radiation is transmitted through an object to recreate an image of the object based on its x-ray absorption (Fig. 1-4). The intensity of the transmitted radiation beam is given by the equation: I = I0e− µx where: I0 is the incident intensity of an x-ray beam on the surface of an object of thickness x

I is the transmitted intensity e is Euler’s constant (2.718) µ is the linear attenuation coeficient Attenuation of an x-ray beam with a particular spectrum depends on two distinct properties of the tissue: the atomic number and the density of the attenuating material. When collecting one projection, it is not possible to determine what combination of atomic number and density resulted in the measured attenuation. Thus both very dense materials (e.g., bone) and materials with a high atomic number (e.g., iodine contrast media) produce strong attenuation. Both would have a similar appearance on CT even though they have very different physical properties. The key advantage of dual-energy and spectral CT techniques (discussed later) is that they can be used to probe the attenuation arising from density and atomic number separately by making two different measurements of the same sample, object, or body part.

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CHAPTER 1

Imaging Principles in Computed Tomography

The transmission of the beam (the ratio I:I0) determines the signal that is collected by the CT scanner detectors at each projection angle, and the attenuation differences along different paths through the patient’s body result in the patterns that are formed in the data for each projection acquisition.

CT Reconstruction and Image Display Overview Once the 1D projection radiographs have been collected, they are transformed into the cross-sectional image to be displayed to the user. There are several approaches to image reconstruction, broadly classiied as iltered backprojection (FBP) and iterative reconstruction (IR) techniques. All of these methods use computerized mathematical operations to combine the 1D projection attenuation information into 2D maps of the attenuation of the scanned subject.

CT Number Scale The reconstructed CT image is a map of tissue attenuation, and these maps are quantitative owing to the use of a scale called the Hounsield unit (HU) scale. The scale is named for the inventor of the x-ray CT scanner, Sir Godfrey Hounsield. The HU scale is a relative scale for linear attenuation of the tissues. It is valuable to quantify the pixel values so that the physician can compare the composition of one tissue with another. The HU scale is based on relating all measured attenuation values to the attenuation of water. A CT numbering system that relates a CT number to the linear attenuation coeficients of x-rays in different absorbers compared to water is given by: CT Number =

K (µ − µw ) µw

where: µw equals the attenuation coeficient of water µ is the attenuation coeficient of the pixel in question When K = 1000, the CT number scale is the HU scale. Other K values can be used to change the scaling of the entire system. When the HU scale is used, air has a value of −1000 HU, water has a value of 0 HU, and dense bone has a value of +1000 HU. The advantage of the HU scale is that density differences of 1 part in 1000 (0.1%) can be represented by distinct values. The inherent density resolution of CT scanners is about 0.5%, so the HU scale is suficient to display all attenuation differences the scanner can measure. Increasing the value of K would not improve on the density resolution of the system. As a general rule, the human eye cannot appreciate contrast differences of less than about 10%, whereas CT scanners can easily demonstrate differences of less than 1%. Thus the small density-resolution difference measured by the CT scanner must be exaggerated for viewing. This is accomplished by enabling the user to select a small range of gray levels from the entire CT number scale and to reset the black and white limits. This is done automatically for many scanners by presetting an appropriate “window/level” setting to be used for display; this setting can be modiied by the user, both on the scanner and when the image is displayed on other workstations and picture archiving and communication systems (PACS).

GENERATION OF A CT IMAGE Components of a Data Acquisition System Gantry. Modern CT systems use slip ring technology to permit the scan frame to rotate continuously for spiral or helical CT scanning. Slip rings are used to transmit power and some control signals to the system components mounted on the gantry rotor. Systems with many

5

detector elements and data input channels use broadband wireless communication to transmit collected image data from the detector assembly to a receiver on the stationary base of the scanner. To enable high-speed scanning with good temporal resolution, CT system developers have focused on providing high gantry rotation speeds. For high-performance systems with mechanical roller gantry bearings, gantry rotation times of 0.33 seconds are achievable.63 Operating modes are available to acquire data over a partial arc (1 minute per image) because of acquisition sequence design, hardware limitations, and the requirement for higher spatial resolution.65,120 However, because of improvements in the acquisition sequences and hardware improvements, DCE-MRI can now be acquired as a volume data set

with a temporal resolution of approximately 3 seconds.68 DCE-MRI can be used to measure perfusion and permeability simultaneously but has to have both a high temporal resolution and a suficiently long acquisition time of approximately 8 to 10 minutes.68,113 DCE-MRI measures of perfusion have a lower contrast-to-noise ratio (CNR) than DSC-MRI does because of its lower T1 relaxivity in comparison with the high T2* relaxivity in DSC-MRI. This drawback can be largely mitigated when imaging highly vascularized cerebral tumors, where high drug concentrations can be reached.10,48

DCE-MRI A complete DCE-MRI study usually includes baseline T1 mapping, dynamic data acquisition, arterial input function measurement, and dynamic data analysis. In the following sections, we will discuss each part of the whole process. DCE-MRI images can be analyzed by using a heuristic method or a suitable tracer-kinetic model to get the proper physiologic metrics related to perfusion and permeability. For convenience, all physiologic parameters in this chapter are summarized in Table 5-2 for later reference.

Baseline T10 Measurement The baseline longitudinal relaxation time T10, before drug injection, is required for pharmacokinetic modeling analysis. Several methods can be used to measure T1. The variable lip angle (VFA) method is one of most widely used methods, calculating a T1 map by using multiple spoiled gradient echo acquisitions with different lip angles.9,22,42 The VFA method allows rapid high-resolution threedimensional (3D) acquisitions because of the modern implementation with very short repetition time.22 Radio frequency (RF) ield (B1)

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CHAPTER 5 TABLE 5-2

Contrast-Enhanced Magnetic Resonance Imaging

83

Summary of Physiologic Parameters Modeled in DCE- and DSC-MRI

Category

Parameters

Normal Range

Unit

Interpretation

Perfusion

Fp vp

20-400 1-30

mL/min/mL %

Mixed

Ktrans kep PS

E × Fp Ktrans/ve 0.01-0.1

1/min 1/min mL/min/100 mL

ve

20-30

%

E τ

∝PS < 10-20 60-65 years),53 loss of consciousness greater than 5 minutes,73 worsening level of consciousness, failure to improve over time,76 periods of transient amnesia or confusion,76,138 and headache with episodes of vomiting.8,53,73,76,136,137 Scanning should be performed more liberally in those on anticoagulation therapy or with bleeding diatheses73 and should be routinely performed for depressed skull fractures.73,76,121 CT is also important in allowing the neurosurgeon to clear patients prior to surgical treatment of non–life-threatening extracranial injuries.65 In unconscious patients, ixed dilated pupils are a sign of herniation requiring urgent imaging and decompression.65 Deteriorating mental status and delayed development of coma may relect evolving secondary injury with worsening ICP and herniation or brainstem compression. DAI, which may not be apparent on CT, can also be the sole source of posttraumatic coma.36,129 Because of the time, resources, and logistics involved in MR scanning, particularly in polytraumatized patients with anesthetic and monitoring equipment, CT has long been used as the workhorse to screen patients for prognostic indicators for surgical intervention and for following the dynamics of lesion development,14,16,17,73,76,81,101,111 although MRI remains an important problem-solving tool. Any focal lesions detected on CT, regardless of size, require follow-up CT scanning. New lesions will arise in around 15% of patients, and 25% to

CHAPTER 13

A

Traumatic Brain Injury

C

B

E

D

FIG 13-8 A, Nonhemorrhagic contusions in the frontal and temporal regions are dificult to distinguish from a background of diffuse cerebral edema and extensive SAH at CT in this 38-year-old following a motor vehicle accident. B, T2-weighted image better shows the extensive contrecoup cortical contusions. The suprasellar and quadrigeminal plate cisterns are completely effaced, consistent with uncal and descendant transtentorial herniation, respectively. C, Uncal and transtentorial herniation is seen on sagittal T1-weighted image. Basal cisterns are completely obliterated. D, DWI shows lesional and perilesional cytotoxic edema in and around the regions of contusion. E, Corresponding low ADC in the contused areas conirms the high signal on DWI is from cytotoxicity rather than T2 shine-through, which would be seen in vasogenic edema. Restricted diffusion due to concurrent DAI is also seen in the corpus callosum.

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FIG 13-9 This 36-year-old bicyclist was struck by an automobile. A, At CT, extensive bilateral contusions were shown to result in complete effacement of the suprasellar cistern from uncal herniation (white arrows) and near-total obliteration of the quadrigeminal plate cistern (black arrow) from descendant transtentorial herniation. This resulted in infarction of the superior right cerebellar hemisphere from compression of the superior cerebellar artery, which arises near the tip of the basilar artery and courses around the midbrain. B, DWI shows infarct of the superior right cerebellar hemisphere, resulting from compression of the superior cerebellar artery from uncal and descendant transtentorial herniation. The infarct may have also been caused by vasospasm from large central subarachnoid hemorrhage. C, At ADC, an area of low signal intensity corresponding with the territory of high signal on DWI is seen, conirming infarct.

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PART II CT and MR Imaging of the Whole Body 45% of cerebral contusions will signiicantly enlarge81 (see Fig. 13-7). CT progression generally occurs within 6 to 9 hours after injury.81,96 CT facilitates a preemptive approach in which surgery is used to prevent deterioration rather than treating lesions once neurologic deterioration has already occurred.81 This strategy has been shown to improve outcome.20,119 CT is also used to determine the need for ICP monitoring.81,95 In general, ICP should be monitored in all patients with clinical evidence of severe TBI (GCS of 3-8) and any abnormal indings on CT.68,95

STRATIFYING INJURY SEVERITY WITH CT CT signs that have been correlated with increased ICP, coma, and death include midline shift greater than 3 to 5 mm (see Figs. 13-4 and 13-5), obliterated basal cisterns87,88 (see Figs. 13-3, 13-8, and 13-9), diffuse hemispheric swelling, SDHs greater than 10 mm in thickness27,68,70,153 (Fig. 13-11), EDHs greater than 15 mm in thickness65,68,75,77,113 (see Figs 13-5A and 13-6B), SAH, and IVH.27,68,80,106,122 Any intracranial mass lesion may warrant surgical evacuation, whether intracerebral hematoma (ICH), hemorrhagic contusion, SDH, or EDH once the size is large enough to cause brain distortion and elevated ICP.148 SDHs have a higher mortality than acute EDHs,68 which may seem counterintuitive given that EDHs often have an arterial source. However, the force required to separate the dura from its periosteal attachment to the inner table of the calvarium is considerable, whereas SDHs can continue to increase with little restriction as additional bridging veins tear when stretched beyond their capacity. Signiicant improvement in mortality is seen when SDHs are evacuated less than 4 hours after

FIG 13-10 Evolving encephalomalacia replacing contrecoup contusions in a 41-year-old woman after motor vehicle collision (arrow). There is associated ex vacuo dilation of the right temporal horn.

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B FIG 13-11 A, CT in an 82-year-old after a fall from ladder shows a hemorrhagic contusion in the right frontal region (arrow), with subdural blood (open arrow) that likely migrated from the contusion through a tear in the arachnoid into the subdural space. The holohemispheric SDH is greater than 1 cm in thickness and is associated with bulk right hemispheric swelling and marked leftward transfalcine herniation. B, Marked transfalcine herniation has resulted in entrapment of the left temporal horn (solid arrow), and there is associated locoregional transependymal spread of CSF (open arrow).

CHAPTER 13 injury.119,148 Intraparenchymal mass lesions typically result in less mass effect than extraaxial hemorrhagic mass lesions and are less ominous predictors of poor outcome27; contusions or ICHs, however, particularly in elderly patients with low GCS scores, are likely to beneit from prompt intervention.44,76 Classiication systems relying on mass effect and mass lesions on CT are limited in patients with DAI.81

CT Findings in Primary Injury Cortical Contusions. Contusions are common, occurring in 43% of closed head injuries, frequently with coexisting coup and contrecoup injuries,76 and can be multiple or solitary.10 Cortical contusions represent bruising and laceration of the brain and primarily involve gray matter. Contusions are often based at the cortical surface and extend toward the center of the brain.10 On noncontrast CT, contusions appear as peripheral low-attenuation areas76 with loss of gray-white differentiation, relecting the combination of cytotoxic edema and vasogenic edema involved. In most cases, some hemorrhage is present at MRI, but this may not be detectable at irst with CT. When contusions are nonhemorrhagic on MRI, they may also be dificult to appreciate on CT,38,54 with subtle areas of low-density edema68 (Fig. 13-12). Hemorrhagic contusions may take the form of multiple areas of microhemorrhage interspersed with low density, giving a heterogeneous “salt-and-pepper” appearance73 (see Fig. 13-3A), or they may appear as more coalescent areas of hemorrhage, giving a more uniformly hyperdense appearance76 (see Fig. 13-7B). As the injury progresses, small hemorrhages may coalesce into larger hematomas.70

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result from shear-induced hemorrhage and rupture of small intraparenchymal vessels. Unlike contusions, these often occur in areas of otherwise normal-appearing brain and initially have less surrounding edema.73 These often occur within frontotemporal white matter, sparing the cortex. Deeper lesions may occur in the basal ganglia, but bleeding in this area may also suggest a possible hypertensive hemorrhage.73 ICHs can be a marker of concurrent DAI even when typical hemorrhagic foci at the gray-white matter junction are absent on CT73 (Fig. 13-14).

Diffuse Axonal Injury. DAI is thought to be present in over 50% of severe head injuries and in more than 85% of severe head injuries resulting from motor vehicle accidents.58 The key point to remember is that DAI is more the rule than the exception in severe TBI patients. DAI presents with the classic CT indings of petechial hemorrhage (an indirect sign of axonal injury) in only 10% to 50% of cases50,68,76,91,94,107 (Fig. 13-15). DAI can be appreciated on CT when small hemorrhagic foci are evident, typically occurring at the gray-white junction (Fig. 13-16) and, in more severe cases, in the corpus callosum complex, which includes the septum pellucidum, fornix, and choroid. Hemorrhagic DAI can also occur in the periventricular white matter at the corner of the frontal horns and in the hippocampal and parahippocampal areas, internal capsule, and cerebellum37,105 (Fig. 13-17). Common areas of hemorrhage should be examined very thoroughly for minimal lesions.10

Subdural Hematoma. In general, the incidence of SDH and EDH is Intracerebral

Hematoma. Whereas ICHs can result from

coalescent hemorrhage in contusions (Fig. 13-13), deeper lesions often

A

higher when skull fractures are present.10,82 SDHs occur along the convexities, tentorium, and falx in descending order of frequency.68

B FIG 13-12 Images of a 37-year-old male pedestrian struck by a car. A, Hypodensity is seen in the bifrontal regions, right (open arrow) greater than left. There is sulcal SAH (solid arrow), but no intraparenchymal hemorrhage is appreciated. B, On FLAIR, nonhemorrhagic cortical contusions corresponding to the areas of low density on CT are visible (open arrow). The acute subarachnoid blood appears as low signal intensity on T2/FLAIR (solid arrow). The round area of low signal intensity in the right frontal region corresponds with an extraventricular drain seen in A. Continued

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D FIG 13-12, cont’d C, On SWI, which is highly sensitive to para- and ferromagnetic substances in blood, the SAH is redemonstrated. Tiny foci of subarachnoid blood are also seen on the right. D, On DWI, cortical contusions are apparent in a wider distribution than what is appreciable on FLAIR.

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B FIG 13-13 Images of a 70-year-old man after a rollover motor vehicle collision. A, Right frontal intracerebral hematoma (open arrow) resulting from coalescent hemorrhage in a contusion deep to a complex skull fracture (shown with volumetric imaging in B). There is an overlying SDH, likely resulting from active bleeding arising from the intraparenchymal hematoma, with a relatively low-density area representing liquid blood (solid arrow). There is also scattered SAH. There is a depressed “eggshell” fracture involving the vertex (B) and vertically oriented displaced fractures propagating down the frontal and parietal bones on the right.

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FIG 13-14 Images of a 68-year-old following a motor vehicle collision. A, CT shows intraparenchymal hematoma with thin halo of edema in the left temporal region, sparing the cortex, and surrounded by otherwise normal-appearing brain parenchyma. B, Low T2 signal within the intraparenchymal hematoma on FLAIR, with surrounding high signal, corresponding with the acute hemorrhage and rim of edema seen at CT. C, On SWI, blooming artifact accentuates the deoxyhemoglobin within the intraparenchymal hematoma. Foci of hemorrhage are also seen at SWI throughout the gray-white junction of the bilateral convexities (D), along the septum pellucidum, splenium of the corpus callosum, and within the lateral ventricles (E).

SDHs follow dural relections, spreading out along the anterior or posterior falx cerebri and typically the supratentorial aspect of the tentorium cerebelli (Fig. 13-18), which may be symmetric or appear as asymmetric high density68 (Fig. 13-19). Unlike EDHs, SDHs are not restricted by suture lines.68 SDHs are usually described as being crescent shaped,10 in contradistinction to EDHs, which dissect between the dura and inner table, resulting in a biconvex (“lentiform”) appearance. The density of acute SDH is high because of clot formation and retraction (see Fig. 13-7A). Density is highest in the irst week after injury and then gradually decreases with protein degradation and liquefaction.73 In acute SDHs, heterogeneity can result from active bleeding9,68,73 (see Fig. 13-13A). SDHs may appear isodense to brain parenchyma in the acute setting if there is severe anemia or traumainduced coagulopathy or when there is admixture with subarachnoid luid crossing through an arachnoid tear68 (Fig. 13-20). Diffuse underlying cortical swelling is common with SDH10; 85% of cases of diffuse swelling and bulk enlargement of a cerebral hemisphere are associated with SDHs.79

Epidural Hematoma. EDHs are relatively uncommon, occurring in approximately 4% of head trauma patients.76 EDHs mostly occur

in young adults. In the elderly, the dura is more strongly afixed to the skull, and in children, plasticity of the calvarium mitigates against EDH. In 91% of EDHs, a skull fracture is seen on CT70,152 (see Fig. 13-5). EDH typically occurs at the site of impact (coup site) in contradistinction to SDH.148 As EDHs dissect along the tightly adherent inner table and dura, the shape formed by the leading edges is well deined.10 As with SDH, mixed density may indicate active bleeding. Areas of often central and irregular low density within hyperdense hematoma, representing admixture of liquid blood and fresh clot, has been termed swirl sign.10,152 Low-density liquid blood can also occur eccentrically or peripherally (see Figs. 13-5 and 13-6). Low-density liquid blood with an EDH is associated with massive hemorrhage and poor outcome.41 Unlike SDHs, EDHs cross dural relections. EDHs usually do not cross suture lines unless the sutures themselves are disrupted or diastatic (Fig. 13-21). The sagittal sutural line is an exception because the dura is not as tightly attached to the periosteum as it is elsewhere73 (Fig. 13-22). Occipital EDHs, often venous in origin, can extend both across the midline and above and below the tentorium (Fig. 13-23), whereas SDHs are restricted by dural relections (Fig. 13-24). Venous EDHs may cause the dural sinuses to be displaced away from the inner table of the calvarium68 (see Fig. 13-21C). Venous

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FIG 13-15 Images of a 20-year-old woman following a motor vehicle collision. CT at the level of the corpus callosum (A) and at the level of the basal ganglia (B) show no visible foci of hemorrhage, but in A, there are small foci of intraventricular hemorrhage in the occipital horns. C, At SWI, numerous petechial foci of hemorrhage are seen in classic locations, including the septum pellucidum, choroid, and splenium of the corpus callosum. D, More caudally, foci of hemorrhage are also seen in the basal ganglia. E, On conventional T2*GRE, foci of hemorrhage are less conspicuous and fewer in number than at SWI. Several petechial foci are seen in the right basal ganglia and right parahippocampal region. F, On DWI, several nonhemorrhagic foci of DAI are identiied in the deep white matter along the bodies of the lateral ventricles (arrows) that were not appreciated on the other sequences. These foci show restricted diffusion on the ADC map (G). H, On the FLAIR sequence, CSF is nulled out. The bright signal within the parietal sulci represents subacute subdural blood (arrows). I, The SAH is obscured on conventional T2-weighted imaging because the CSF is also bright.

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FIG 13-16 This 22-year-old suffered DAI after a motor vehicle collision. A, At CT, a small hemorrhagic lesion is seen at the parasagittal gray-white matter junction near the vertex (arrow). B, FLAIR shows the more extensive shear injury in this region, most of which was not appreciable on CT. Additional areas of DAI are revealed with FLAIR in the left basal ganglia (C), right parahippocampal region (D [open arrow]), and dorsolateral brainstem (D [solid arrow]). E, Hemorrhage is more conspicuous in the same areas at SWI.

A

B FIG 13-17 A, Several hemorrhagic lesions are seen at the corner of the right frontal horn in a 31-year-old with DAI following motor vehicle collision. B, At SWI, much more extensive hemorrhagic lesions are apparent in the same region at the corner of the right frontal horn, also involving the genu of the corpus callosum. Lesions not apparent on CT are revealed in the left basal ganglia (solid arrow) and fornix (open arrow).

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B FIG 13-18 A 19-year-old with TBI following a motor vehicle accident. On CT, acute SDH is seen propagating along the posterior falx (A [arrow]), and tentorial lealets (B [arrows]).

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B FIG 13-19 A 40-year-old woman with TBI following a motor vehicle accident. A, A high-density SDH is seen spreading out along the right tentorial lealet. Unlike EDHs, SDHs may be indistinct and can blend with SAH, seen in B in the quadrigeminal plate cistern (solid arrow). A small focus of SAH is also seen in the interpeduncular cistern (B [open arrow]).

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FIG 13-20 Images of a 25-year-old driver of a sedan that was “run over” by a tractor trailer. The patient sustained injury to multiple body regions and large-volume resuscitation. A, A thin isodense right SDH is barely perceptible on head CT, even with the use of low-level wide window settings, which accentuate subdural blood. There is resultant bulk hemispheric swelling on the right, resulting in a 3-mm leftward midline shift. B, An image from the arterial phase neck CT is shown. There is displacement of the cortical vessels away from the inner table of the calvarium (arrows). C, On the contralateral side, vessels extend all the way to the inner table (arrow).

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FIG 13-21 A 21-year-old after a fall while skateboarding. A, A biconvex epidural hematoma is seen, which crosses the lambdoid suture. An indentation of the dura (arrow) is seen immediately over the suture, likely representing the prior point of sutural attachment. B, Diastatic lambdoid suture is shown on bone window (arrow). C, CT venogram shows a distorted extrinsically narrowed left transverse sinus displaced off the inner table of the calvarium (arrow), with overlying (likely venous) EDH and sutural diastasis.

EDHs (representing only 15% of EDHs overall) typically occur in three locations: the posterior fossa from torcular injury, middle cranial fossa from sphenoparietal sinus injury, and vertex from injury to the superior sagittal sinus.73 Venous EDH also occurs in the regions of the transverse and sigmoid sinuses.68,70 These EDHs tend to enlarge less quickly than arterial EDHs.

Intraventricular Hemorrhage. IVH is uncommon, occurring in approximately 3% of newly diagnosed cases of TBI, but it contributes signiicantly to morbidity and mortality, with half of patients with IVH developing increased ICP, and 10% requiring ventricular drainage.76 IVH usually appears as a hyperdense blood-luid level layering dependently in the ventricular system.73 In small hemorrhages this can be

subtle, with punctate foci appearing in the tips of the occipital horns (see Fig. 13-15A). Occasionally IVH may appear tumefactive as a cast within the ventricle73 (Fig. 13-25).

Subarachnoid Hemorrhage. SAH occurs in 40% of cases of moderate to severe head injury and is usually associated with other types of intracranial hemorrhage.68 The volume of extravasated blood is rarely as large or extensive as in aneurysmal SAH and more often has a peripheral distribution, sometimes adjacent to areas of cortical contusion.70,111 Acute SAH is readily identiied on noncontrast CT as linear and serpentine areas of high attenuation extending into and conforming to the cerebral sulci and sylvian issures without mass effect68,73 (Fig. 13-26; see also Fig. 13-12A). SAH along the convexity, tentorium,

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B FIG 13-22 A 21-year-old after a fall from height. A, EDH is seen over the vertex on coronal CT. B, This crosses the midline and results in sagittal suture and coronal suture diastasis, seen on volumetric 3D CT image.

A

B FIG 13-23 This 17-year-old sustained an occipital bone fracture after a fall from height and was found to have an EDH (A), which enlarged on short-interval follow-up CT (B). The EDH extended above (A) and below (B) the tentorium. Areas of low density correspond with active bleeding.

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B FIG 13-24 A, Occipital SDH in a 71-year-old woman after a fall from standing. Unlike occipital EDHs, SDHs do not cross dural relections. B, Sagittal reformatted image shows the SDH coursing along the inferior aspect of the tentorium.

or falx can be dificult to differentiate from SDH.73 Small foci of SAH at the interpeduncular cistern may be easily missed without conscious attention to this area68 (see Fig. 13-19B). Although SAH is usually associated with other indings, it may be the sole inding in a minority of cases.68,122 In the subacute setting, SAH becomes isodense and may be very subtle; effacement of sulci may be the only imaging clue.73 The reason for increased mortality is uncertain but is hypothesized to be related to vasospasm.27

CT OF SKULL FRACTURES There are three main types of skull fractures: linear and depressed calvarial fractures and basilar fractures. Linear fractures are the most common, seen frequently with falls from standing,102 and are least likely to be associated with intracranial injury. Linear fractures of the calvarium are easily appreciated on axial CT images if the plane of the fracture is vertically oriented. Axially oriented fractures can be easily missed but are better seen on multiplanar reformats (see Fig. 13-5B) and three-dimensional (3D) volume rendered images70; 3D images are also useful for depicting comminuted and depressed fractures. Basilar fractures are best evaluated with dedicated thin-section scanning (see Fig. 13-25D). Depressed or markedly displaced fractures are more commonly associated with intracranial abnormalities such as dural tears, which can result in CSF leak. Thin-section CT has been shown to be both more sensitive than radionuclide or CT cisternography for identifying the site of leak (commonly near paranasal sinuses and mastoid air cells) and correlates more closely with operative indings78,139 (Fig. 13-27). Depressed fractures can also cause arachnoid tears, which can result in low-density hygromas. Depressed fractures are explored and repaired, and bone fragments elevated both for cosmesis70 and to prevent additional cortical laceration, dural tear, or vascular injury by sharp bony fragments. In general, open skull fractures depressed more than the full thickness of the skull should be surgically

elevated.76 Débridement may be necessary if there is signiicant fragmentation of the skull.65

CT of Vascular Injuries Vascular injuries are commonly related to skull base fractures. CT venogram may be warranted for fractures that propagate in the region of the transverse and sigmoid sinuses. CT venography is at least as accurate as MR venography for dural venous sinus thrombosis (DVST) and is better at visualizing small cerebral veins104 (Fig. 13-28). In the absence of a fracture line extending to a dural venous sinus or jugular bulb, the likelihood of traumatic DVST is very low.23 On the other hand, when skull fractures extend to a dural sinus or jugular bulb, approximately 40% will have DVST, which is occlusive in over half of cases and is associated with hemorrhagic venous infarct at MRI in 7%.23 Arterial injuries may occur with skull base fractures extending through the petrous temporal bone into the carotid canal or propagating through the sphenoid in the vicinity of the cavernous carotid.70 These fractures warrant further evaluation with CT angiography (CTA) because vascular injuries can result in infarcts and cerebral ischemia.20,73 Carotid cavernous istulae are characterized by asymmetric enhancement of the cavernous sinus and venous engorgement, especially of the superior ophthalmic vein and inferior petrosal sinus,73 as well as enhancement of draining veins73 (Fig. 13-29). CTA offers slightly improved spatial resolution compared to current MR angiography (MRA) protocols, with fewer low-related artifacts and better delineation of adjacent bony anatomy45,76,146; however, MRA allows follow-up of injuries without additional exposure to ionizing radiation. In addition to skull base fracture, neck trauma is another major risk factor for cerebral infarction, and neck CTA is often performed concurrently. Bilateral segmental wedge-shaped areas of low density and loss of gray-white differentiation on noncontrast head CT can suggest thromboembolic phenomena from blunt cerebrovascular injury (Fig. 13-30).

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D FIG 13-25 TBI and skull base fracture in a 28-year-old following a motorcycle collision. Patient had previously undergone decompressive frontotemporoparietal craniectomy. Two weeks after the initial injury, he developed delayed intraparenchymal hematoma (A) and substantial IVH, which formed casts within the lateral, third, and fourth ventricles. B, Tumefactive IVH in the third ventricle is shown (arrow). C, A repeat CT angiogram revealed the source of hemorrhage to be a newly formed pseudoaneurysm of the right anterior cerebral artery (arrow). D, Skull base fracture extending through the sphenoid is shown.

CT PERFUSION Perfusion CT is frequently used in acute stroke but may have a role in TBI patients,76,149 in whom abnormalities on perfusion CT relect abnormalities in autoregulation. Patients with minor head trauma and intact autoregulation will maintain or have slightly increased cerebral perfusion, whereas patients with severe injury have impaired autoregulation and pressure-passive low, resulting in oligemia and decreased perfusion68 (Fig. 13-31). Multiple sequential dynamic images are required for perfusion CT to track contrast material as it passes through the brain,76 and high radiation dose remains a concern,68 although radiation doses are lower with newer MDCT scanners,

improved detectors, and low mAs protocols. Normal perfusion or hyperemia (high cerebral blood volume [CBV] and cerebral blood low [CBF]) are associated with favorable clinical outcomes, whereas oligemia (low CBV and CBF) are associated with unfavorable outcomes68,76,149 (Fig. 13-32).

LIMITATIONS OF CT CT can miss small amounts of blood, linear fractures, and foci of pneumocephalus, owing to volume averaging.76 Beam hardening limits evaluation of the posterior fossa, frontal, and temporal regions.20,64,76 CT indings may lag behind clinical deterioration, and exams

FIG 13-26 In the 21-year-old woman shown in Figure 13-1, DAI was not apparent on CT, but focal SAH was seen within right frontal lobe peripheral sulci (arrow). There is a large overlying right frontal scalp contusion and hematoma.

FIG 13-27 Coronal CT of the face of a 17-year-old with CSF rhinorrhea shows fracture of the left planum sphenoidale (arrow), which also extended to the cribriform plate (not shown). The CSF leak was successfully treated with shunting.

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FIG 13-28 A, CT of a 20-year-old after motor vehicle collision. High-density material is seen in the expected location of the left sigmoid sinus. B, CT venogram showed segmental nonilling in keeping with occlusive thrombus in the left sigmoid sinus (arrow). C, MR venogram without gadolinium shows loss of low-related enhancement from occlusive thrombus in the left sigmoid sinus (arrow). D, Full-volume maximum intensity projection (MIP) image from MRV conirms lack of low in the distal transverse sinus, sigmoid sinus, and jugular bulb. E, Sagittal T1-weighted image shows high signal thrombus within the transverse and sigmoid sinus (arrows). F, Temporal bone CT shows fracture involving the petrous and squamous temporal bone extending through the sigmoid notch.

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FIG 13-29 In this 37-year-old pedestrian struck by a car, asymmetric opaciication of the cavernous sinus (A) and engorged early draining right ophthalmic vein (B [arrow]) were highly suggestive of carotid cavernous istula, later conirmed angiographically and treated with coil embolization.

performed within several hours of trauma may underestimate injury.29 There is still debate over whether CT scans should be repeated after normal admission CT.76,126

MRI IN PRIMARY INJURY MRI is superior to CT for many forms of posttraumatic lesions,3,37,67,77,103,111 although skull fractures are a major exception.10,103 MRI is often reserved for screening for focal or diffuse parenchymal lesions in the setting of a CT scan that does not adequately explain depressed consciousness.10,70,111 This includes DAI (see Figs. 13-1 and 13-14 through 13-17) and nonhemorrhagic contusions77,111 (see Figs. 13-8 and 13-12). Owing to its multiplanar capabilities, MRI is far superior to CT for detecting herniation, especially through the tentorial incisura and foramen magnum30,37,76 (see Figs. 13-8B and C). MRI is also better for characterizing injury evolution and recognizing complications, and for characterizing degenerating blood products, which vary in signal intensity with time.

Intraparenchymal Injury A variety of MR sequences can be used concurrently to identify, characterize, and determine the extent of focal brain injuries. Because luid-attenuated inversion recovery (FLAIR) nulls the high signal from CSF, this sequence is sensitive for detecting periventricular lesions such as foci of DAI (see Figs. 13-1, 13-14B, and 13-16B-D) as well as supericial cortical contusions20,73 (see Figs. 13-3B and 13-12B) and vasogenic edema.3,73,76 Gradient echo images (GRE) are T2* weighted and sensitive to magnetic susceptibility effects of para- and ferromagnetic substances112,144 (see Fig. 13-15E). In recent times, GRE has been all but supplanted by susceptibility-weighted imaging (SWI). Unlike GRE,

SWI enhances contrast of magnetic susceptibility by combining magnitude and iltered phase images from a high-resolution 3D gradient. SWI has been shown to be up to 5 or 6 times more sensitive to hemorrhage than GRE8,112,118,120,142 and is less prone to artifacts at air-tissue interfaces.39,46,132 SWI is highly sensitive to ield inhomogeneities caused by paramagnetic substances, including deoxyhemoglobin and intracellular methemoglobin, and is also highly sensitive for detecting ferritin and hemosiderin, which are both ferromagnetic.8,20 SWI is therefore useful for detecting hemorrhage in acute, subacute, and chronic phases. One major disadvantage of SWI is that images take longer to perform than GRE and can easily be degraded by motion in agitated patients.39 Diffusion-weighted imaging (DWI) detects decreases in random brownian motion in injured swollen cells, resulting in bright signal on DWI as water moves from the extracellular to intracellular space.20,70 DWI is sensitive to acute cytotoxic edema and by extension is highly sensitive for detecting nonhemorrhagic traumatic lesions (see Figs. 13-8D, 13-12D, and 13-15F).

Contusions and Intraparenchymal Hematomas On MRI, hemorrhagic contusions and intraparenchymal hematomas appear as ill-deined areas of mixed signal intensity on T2-weighted images73 (see Fig. 13-7C). Because cerebral contusions primarily involve the periphery of the brain, contusions often have a gyral morphology73 (see Figs. 13-8B and 13-12). Nonhemorrhagic contusions may be dificult to detect initially on conventional sequences, including FLAIR, but the resultant cellular dysfunction causes early cytotoxicity. Restriction on DWI may occur as early as 1 hour after injury51 and gives a more accurate estimate of the true extent of injury than FLAIR10,70,73 (compare Fig. 13-12B and D). High signal on DWI can also be caused by T2 shine-through from vasogenic edema, and images

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FIG 13-30 A, Volume-rendered image from neck CTA shows left carotid artery pseudoaneurysm (arrow) in a 27-year-old pedestrian struck by a car. B, Bilateral wedge-shaped hypodensities with loss of gray-white matter differentiation are seen at the convexities, in keeping with embolic infarcts. C, Filling defect from embolized thrombus is seen in the proximal left MCA. D, DWI shows large area of restricted diffusion consistent with left MCA territory infarct.

must be interpreted together with apparent diffusion coeficient (ADC).8,26,57 DWI does not routinely distinguish between cytotoxic edema from trauma and cytotoxicity from ischemia, but the latter is suggested by a vascular distribution rather than perilesional involvement (compare Fig. 13-31D and E).

Brainstem Injuries A very small percentage of brainstem lesions are seen at CT, owing to beam-hardening.37,52,10,83 Brainstem lesions are encountered in up to 64% of comatose patients after severe head injury.10,33 Contusion of the brainstem can occur in isolation, but this is rare, and concomitant

lesions are seen in most cases.33 Bilateral pontine lesions are associated with poor outcome and are often fatal.18 Decompressive craniectomy or other invasive measures may be medically futile in such cases.33 Primary and secondary brainstem lesions may be distinguishable based on their MR characteristics.33 Direct traumatic brain laceration typically occurs at the dorsolateral midbrain and pons, where these structures can collide posteriorly with the dural relections of the tentorial incisura. Because of the severe forces required to produce shear and direct destruction of tissue in this region, most are hemorrhagic,33 whereas secondary lesions caused by herniation are less likely to bleed.33 Although Duret hemorrhages can occur in brainstem

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FIG 13-31 CTP study and MRI from a 36-year-old bicyclist struck by a car (same patient as Fig. 13-9). The patient has had a decompressive craniotomy, and brain contents are seen herniating through the right-sided craniotomy defect. There is decreased blood volume (A) and blood low (B) within areas of bilateral frontal lobe hemorrhagic contusion, herniating frontotemporal brain contents, and right cerebellar hemisphere infarct (C). D and E, On DWI, corresponding restricted diffusion is seen in all these areas.

herniation, these are usually differentiated from primary traumatic injury by their location in the ventral and paramedian midbrain68,105 (Fig. 13-33). Duret hemorrhages are thought to occur as a result of venous thrombosis or laceration of the pontine perforators of the basilar artery from tension related to caudal herniation of the brainstem.68,70

Diffuse Axonal Injury Even with the best imaging techniques, only a minority of DAI lesions, which are primarily microscopic, can be identiied.58,105 Brainstem injuries are very rarely present in the absence of DAI involving more peripheral structures. Mild DAI (grade I) involves only peripheral gray-white matter junctions; moderate DAI (grade II) involves the corpus callosum (usually the splenium and posterior body); and severe DAI (grade III) involves the dorsolateral midbrain or brainstem.1,68,70,73,105 In the midbrain, the posterolateral area adjacent to the superior cerebellar peduncle is most frequently affected105 (see Fig. 13-1B). DWI is the most sensitive sequence for detecting nonhemorrhagic DAI in the acute setting. Lesions are hyperintense on DWI and hypointense on ADC.58,68 SWI is extremely sensitive for the detection of concomitant microhemorrhages in DAI68,120 (see Figs. 13-14 through 13-17). Although FLAIR is less sensitive for acute DAI lesions, sagittal and coronal FLAIR images can be helpful for detecting DAI involving the corpus callosum and fornix.68,73

Extraaxial Injuries MRI is more sensitive for thin extraaxial “smear collections,” SAH, and IVH when FLAIR is used4,73,76,99 (Fig. 13-34). Hypointensity on T2/ FLAIR is in keeping with acute blood (see Fig. 13-12B), and hyperintensity on T2 suggests subacute bleed or hygroma147 (Fig. 13-35). With SWI, MRI has excellent sensitivity for detecting acute extraaxial hematomas but little added value for this purpose with respect to CT. MRI has greater utility for characterizing extraaxial collections in the subacute and chronic phases, discussed in the subsequent section.

ROLE OF IMAGING IN SECONDARY BRAIN INJURY AND COMPLICATIONS Common indings in secondary brain injury include worsening or new hemorrhage and worsening vasogenic or cytotoxic edema, all of which contribute to increased ICP and can result in herniation, ischemia, and infarction. CT is used to determine the need for extraventricular drain placement, hematoma evacuation, and wide craniectomy,70 and also for monitoring improvement and determining when a bone lap can be replaced (Fig. 13-36). When ICP increases in patients with ICP monitors, CT is performed to exclude delayed traumatic ICH, infarct, or posttraumatic hydrocephalus.148 CT can also screen for

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FIG 13-32 A, CT demonstrates diffuse cerebral hypodensity with relatively increased density of the cerebellum (“white cerebellum sign”) in a 19-year-old pedestrian struck by a car. B, On follow-up CT, the marked diffuse cerebral hypodensity is more apparent (“big black brain sign”). Cerebral hypodensity brings the meninges into relief, which appear relatively hyperdense (pseudosubarachnoid hemorrhage sign). Findings are consistent with anoxic brain injury. Areas of low CBV (C) and low CBF (D) are seen throughout most of the cerebral hemispheres bilaterally, with an area of relative sparing in the posterior left temporal region. High CBV and CBF are seen in the cerebellum, indicating compensatory increased perfusion through the vertebrobasilar circulation. Shortly thereafter, nuclear scintigraphy showed no perfusion of the the cerebral hemispheres, conirming a clinical diagnosis of brain death.

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B FIG 13-33 A, In this 51-year-old with TBI after a fall, SWI shows Duret hemorrhage (arrow) in the midline of the brainstem, emanating from the ventral pons and appearing to arise from the basilar artery (arrow). This likely resulted from injury to a pontine perforating branch. B, More inferiorly, the Duret hemorrhage is seen to continue to extend from the ventral to dorsal pons. Additionally there are two dorsolateral hemorrhagic foci (arrows), consistent with primary traumatic injury resulting from collision of the midbrain with the tentorial lealets.

postoperative complications such as hematomas, which occur in 15% of TBI patients.148 MRI is generally considered diagnostically superior to CT 48 to 72 hours after injury; this is because the ability of MRI to depict the full extent of hematomas improves over time as blood composition changes.76 In the subacute stage, SAH may be isodense to brain parenchyma on CT but is high signal intensity on FLAIR (see Fig. 13-15G). Chronic SAH is also better seen owing to supericial hemosiderosis.73 MRI is better at visualizing and characterizing all herniations because of its multiplanar capabilities. DWI and ADC are exquisitely sensitive for ischemia and infarction resulting from herniation (see Figs. 13-31E and 13-35C) and for characterizing the full extent of both hemorrhagic and nonhemorrhagic contusions (see Fig. 13-12D).

Contusions, Intracerebral Hematomas, and Hypoxic Encephalopathy

FIG 13-34 A thin subacute subdural hematoma is seen along the left convexity (arrow) in a 52-year-old woman after a fall from standing. This is well visualized as CSF is nulled out on FLAIR.

Within the irst week after injury, it is common for hemorrhage within contusions to progress and for large contusions to develop new delayed hemorrhage and worsening edema (see Fig. 13-7). Surprisingly, perilesional edema does not appear to be a strong predictor of subsequent size increases in hemorrhagic contusions.7 Perilesional edema also seems to be uncommon in contusions that do evolve.7 ICHs may develop in a delayed fashion in a part of the brain previously appearing normal on CT; this is known as delayed traumatic ICH.68 In one study, all traumatic ICHs developed within 24 hours of onset, but only 56% of ICHs developed within 6 hours of injury.68,151 With diffuse cytotoxic edema, such as may result from global hypoxic episodes, the

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FIG 13-35 Extraaxial collection is high signal on T2/FLAIR (A) and high signal in sagittal T1-weighted image (B) of a 43-year-old after a fall. The high T1 signal differentiates this subacute hematoma from a subdural hygroma, which would have similar signal intensity to CSF on T1. C, On ADC image, right uncal herniation from SDH and associated cerebral swelling resulted in extrinsic compression of the right PCA and right PCA-territory infarct.

cerebellum and brainstem are usually spared,73 which can result in a “big black brain” appearance, “white cerebellum sign,” or “pseudoSAH”10 on CT, where the cerebellum, dura, and vasculature are brought into relief by the low attenuation of the brain (see Fig. 13-32).

SDH, EDH, and SAH In the course of evolving TBI, SDHs may rebleed. It may be dificult to appreciate this in a heterogeneous subacute SDH, but when new heterogeneity is seen within a previously homogeneous SDH, this is relatively speciic for small amounts of rebleeding. New sedimentation effect is also suggestive of rebleed66,102 (Fig. 13-37). Sometimes a clear interface may be seen along the long axis of a SDH,102 resulting from formed neomembranes in the subacute or chronic setting (see Fig. 13-37). Layered-type SDH has the highest tendency for subsequent rebleed due to hyperibrinolytic activity.100 At 1 to 4 weeks after bleeding, extraaxial hematomas are generally isodense to brain parenchyma, making them dificult to detect on CT.9,10,69,74,76 It is important to use low-level, wide window settings (sometimes referred to as a subdural window) to maximize the likelihood of detecting subacute SDHs.76 Subacute SDHs are suggested by indirect indings such as sulcal effacement, displacement of the gray matter and gray-white junction away from the inner table, regional sulcal effacement, white matter buckling, and midline shift.73 Capsules and neomembranes that have formed around or within a subacute or chronic SDH may enhance on contrastenhanced CT secondary to neovascularity and disrupted blood-brain barrier10,70 (Fig. 13-38). Subacute SDHs are well appreciated at MRI. As collections liquefy, red cells break down, deoxyhemoglobin oxidizes to methemoglobin, and extraaxial collections become hyperintense on T1-weighted images11,76 (see Fig. 13-35B). In the subacute phase, methemoglobin is primarily responsible for variation in T1 and T2 signal intensity.25 Chronic SDH has attenuation similar to CSF both on CT and conventional MR sequences. A new low-density collection not seen on a recent prior exam is highly suggestive of hygroma (Fig. 13-39). MR signal intensity within SDH depends on the evolution of hemorrhage.10 Vasospasm from SAH is especially common in the subacute phase.70

Traumatic Hydrocephalus In the acute setting, traumatic hydrocephalus can result either from impaired resorption of CSF by the arachnoid villi secondary to

arachnoiditis in communicating hydrocephalus68 or obstruction of the third ventricle, cerebral aqueduct, fourth ventricle, and ventricular outlow tracts by blood or extrinsic compression in noncommunicating hydrocephalus73 (see Fig. 13-25). Hydrocephalus appears acutely as dilated ventricles, with sulcal effacement and periventricular low density from transependymal spread of CSF in severe cases.73 Delayed traumatic hydrocephalus is a common complication of traumatic SAH as arachnoid villi become engorged by phagocytes and ibrose68 (see Fig. 13-39). CT helps in determining the need for an extraventricular drain for therapeutic drainage of CSF.148 Although asymmetric ventricles do not have a high predictive value for elevated ICP, dilation/ entrapment of the contralateral temporal horn can result from compression of ventricular outlow at the foramen of Monro, which correlates highly with increased ICP27 (see Fig. 13-11B). The ipsilateral ventricle is usually compressed.73

Traumatic Brain Herniation, Ischemia, and Infarction Traumatic brain herniation occurs secondary to mass effect produced by primary or secondary injuries, resulting in unmitigated increases in ICP.68,73 Common patterns of brain herniation correlate with patterns of compressive and ischemic injury.70 Multiple patterns often occur simultaneously and have overlapping appearances.63 The most common form is subfalcine herniation, where the cingulate gyrus is displaced across the midline under the falx cerebri, resulting in midline shift at CT and MRI68,73 (see Figs. 13-4 and 13-5A). This causes the anterior cerebral artery (ACA) and callosomarginal branches to become trapped, resulting in ischemia or infarction involving the ipsilateral paracentral region and superior frontal gyrus.10,73,114 Uncal herniation, where the uncus of the hippocampus displaces through the tentorial incisura, can be unilateral or bilateral and results in effacement of the suprasellar cistern68,73 (see Figs. 13-8B and C and 13-9A). This can compress the anterior choroidal artery, leading to infarction of the posterior limb of the internal capsule, as well as peduncular and posterior cerebral artery (PCA) territory infarction68,93 (see Fig. 13-35C). Uncal herniation also results in compression of the ipsilateral oculomotor nerve, causing blown pupil.73 In descendent transtentorial herniation, the medial temporal lobes herniate through the tentorial incisura10,48 (see Fig. 13-8B and C). Upward herniation can result from lesions in the posterior fossa, with herniation of portions of the cerebellar vermis or hemispheres.73 Transtentorial herniation causes effacement of the quadrigeminal and

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D FIG 13-36 After a motor vehicle accident, CT showing basal cisternal effacement in this 19-year-old with SDH and SAH (A), together with elevated pressure detected using an extraventricular drain (B), was used to determine the need for wide frontotemporoparietal craniotomy (C). There is mild herniation of brain contents through the right-sided defect in C. Some of the high-density material seen overlying the herniated brain contents is from duraplasty (i.e., dural repair [arrows]). D, Once swelling subsided, a cranioplasty was performed. There has been interval bone absorption of the cranioplasty lap, which can occur with either cryo- or subcutaneous preservation. In this case the lap was cryopreserved.

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CHRONIC SEQUELAE OF TBI Moderate to Severe TBI Approximately 40% of patients with TBI discharged from acute hospitalizations develop TBI-related long-term disability.21,70 Encephalomalacia is a common chronic sequela of parenchymal injury. Small areas of encephalomalacia are often clinically asymptomatic but can serve as seizure foci.73 Encephalomalacia is detected at CT as well-deined areas of simple luid density with volume loss.10,73 On MRI, encephalomalacic areas follow signal intensity of CSF on T1- and T2-weighted imaging. Areas of gliosis at the parenchymal margins are high signal on FLAIR. Encephalomalacia becomes completely cystic 4 to 6 months after trauma10 (see Fig. 13-39B). Other late sequelae of trauma include hydrocephalus, CSF leak with itinerant pneumocephalus, and generalized atrophy.10 In cases of DAI, involved portions of the corpus callosum become shrunken and cystic.2,105

Mild TBI

FIG 13-37 In this 82-year-old man who hit the back of his head after falling out of bed, there is dependent sedimentation effect as well as a clear interface spanning the long axis of the left SDH, separating acute from chronic blood. Both areas of high density represent rebleed. Layered-type SDHs have a high propensity toward rebleeding.

other basal cisterns.68 Infarct can occur in the bilateral occipital lobes or brainstem as the PCAs or distal basilar artery become trapped.70,93 In tonsilar herniation, the cerebellar tonsils herniate into the foramen magnum.61,68,73 Bulk hemispheric mass effect can cause MCA territory infarct. Vasospasm alone can also result in territorial ischemia and infarction.93 Peripheral venous infarcts can be caused by extraaxial hematomas that exert mass effect on the adjacent cortex, compressing cortical veins.68

Postoperative Appearances and Complications Wide craniectomies are performed to decrease ICP by allowing the brain to herniate through the defect, effectively increasing intracranial volume148 (see Fig. 13-31). This often results in rapid radiologic improvement in terms of midline shift and cisternal effacement.68 In diffuse swelling, bilateral decompressive craniectomies are sometimes performed.27,109 Cranioplasty can be performed immediately after evacuation of hematomas (see Fig. 13-6), or the bone lap can be temporarily removed when hemispheric swelling prevents replacement27 (see Fig. 13-36C and D). Duraplasty can be performed after durotomy, and thin extraaxial high density subjacent to the cranioplasty or craniectomy site may represent synthetic dural graft.148 CT and MRI can detect postoperative complications including subdural empyema, abscess, brainstem hemorrhage, edema, tension pneumocephalus, and intracerebral hemorrhage76 (Fig. 13-40). Complications of ventriculostomy can include hematoma, meningitis, and ventriculitis.148

mTBI is especially dificult to diagnose but can result in persistent cognitive deicits in a minority of patients.28,72 Advanced MRI techniques have the potential to help distinguish between organic and nonorganic causes of insidious neuropsychiatric symptoms after mTBI.8 Interest in prognosticating outcomes in cases of mTBI have increased with the recent attention to the long-term consequences in athletes following repeat concussions or subconcussive episodes.8,12,20,22,49,70,111,130,141

SWI and DWI Cerebral microhemorrhages may be an important marker of longterm complications in mTBI49,111 resulting from low grade DAI. This phenomenon has been termed DAI syndrome.129 DWI and SWI can improve the ability to detect axonal shear injury in mTBI cases, but the clinical relevance of this increased sensitivity in the setting of mTBI is still controversial.127,118,117,143,34,111,39,132 Mean ADC values in the whole brain have been shown to be among the best predictors of outcome among all degrees of TBI.34,111

Magnetic Resonance Spectroscopy Although MRS is not widely used after TBI, particularly in the early period after injury,124 it has been shown to be clinically useful and can depict injury in a brain that otherwise appears normal at imaging.13,15,20,35,56 MRS is potentially widely available, as it can be readily implemented on existing MRI machines.20 Within a selected tissue volume, a spectrum of metabolites, including N-acetylaspartate (NAA), creatine, and choline are examined. Heights of each compound correspond with their relative abundance. The NAA peak occurring at 2.0 parts per million (ppm) is a measure of neuronal integrity and mitochondrial function or impairment.70,84 The creatine peak at 3.0 ppm consists of protons involved in the creatine kinase reaction, basic to cellular energy and metabolism.70 At 3.2 ppm, the choline peak consists of protons found in the phospholipid bilayer of cell membranes. Choline is a marker of myelin and cell membrane breakdown.70,111 The creatine peak is relatively stable and acts as a convenient benchmark to gauge the relative abundance of other compounds. Decrease in NAA, indicating axonal or neuronal damage, is seen in the early acute setting after head injury15,20,76,111,115,124, (Fig. 13-41). Lower NAA-to-creatine ratios have been correlated with poorer clinical outcomes.19,35,59,76,124,128 In repeat concussive episodes, the severity of biochemical abnormality depends on the interval between traumatic events, and NAA measurement by MRS may be valid in assessing metabolic recovery.70

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B FIG 13-38 A 63-year-old with acute-on-chronic right SDH after a fall. A, The chronic portion of the hematoma is low density on the noncontrast CT image. Several high-density strands, in keeping with neomembranes, are seen spanning the SDH. An area of high density represents rebleed, which is contained by the formed membranes (arrow). On the left there is a subacute, nearly isodense subdural hematoma. Notice the subtle inward buckling of the cortex. B, Contrast-enhanced CT shows that the formed ibrous membranes traversing the right chronic SDH enhance (arrow). Both the right chronic and left subacute subdural have enhancing capsules (arrows).

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FIG 13-39 A, In this 36-year-old bicyclist struck by a car (same patient as Figs. 13-9 and 13-31) a left hygroma had developed, which was not seen on a recent prior. Hygromas result from arachnoid tears, which allow CSF to enter the subdural space. A single burr hole evacuation was subsequently performed, and the hygroma resolved with drainage. B and C, Brain swelling gradually resolved, and hemorrhagic contusions and right cerebellar infarct were replaced by evolving encephalomalacic changes. Third and fourth ventricles are dilated (B [arrows]) as a result of impaired resorption of CSF at the arachnoid villi. Communicating hydrocephalus is redemonstrated, and there is further evolution of encephalomalacia on follow-up (C).

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FIG 13-40 A 44-year-old with abscess demonstrated on CT (A [arrow]) and sagittal T1 postgadolinium MRI (B [arrow]) after decompressive bifrontal craniotomy for TBI. Because of concurrent osteomyelitis, the lap was replaced with a synthetic cranioplasty implant (C).

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B FIG 13-41 A, MRS in a healthy control shows normal NAA/Cr ratio in the splenium of the corpus callosum. B, MRS in a 40-year-old male mTBI patient with impaired neurocognitive function following a motor vehicle collision shows a relative decrease in the NAA peak compared with the creatine peak, and decreased NAA/ Cr ratio. (From Bodanapally UK et al: Imaging of traumatic brain injury. Radiol Clin North Am 53:695–715, 2015.)

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FIG 13-42 DTI iber tracking at the corpus callosum from a normal volunteer (A) and a 40-year-old woman with mTBI after a fall and GCS of 15 at presentation (B and C). Fiber tracking at the corpus is shown 10 days (B) and 1 month (C) after injury. B and C show temporary loss of visualization of iber tracks in the genu/ anterior body junction of the corpus (B [arrow]), with return of normal low radial and high axial diffusivity, resulting in visualization of tracks in this region at 1 month (C [arrow]). The patient had a normal-appearing brain on conventional MRI sequences, yet acutely impaired cognitive scores, with normal neurocognitive function by 1 month. (From Bodanapally UK et al: Imaging of traumatic brain injury. Radiol Clin North Am 53:695–715, 2015.)

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FIG 13-43 Abused infant with shaken baby syndrome. Right subdural collection, which contained locules that followed CSF on T1-weighted images and T2/FLAIR, consistent with hygroma or chronic subdural hematoma (A and B [solid arrows]), and other areas that were high signal intensity on both T1 (C [solid arrow]) and T2, consistent with subacute SDH. Areas of gliosis (high FLAIR signal) and dystrophic calciication (high T1 signal) are seen in the occipital lobes, more prominently on the right (A and C [open arrows]). The child was found to have retinal hemorrhages on funduscopic exam.

Diffusion Tensor Imaging Unlike scalar measures such as ADC, a tensor provides information about directional diffusivity by derivation of “eigenvectors,” which correspond with the three orthotopic axes of a white matter tract’s direction.5 Unlike conventional DWI, which encodes diffusion in three axes, an effective diffusion tensor is determined with DTI by assessing diffusion in up to 25 to 30 directions.68 The directionality of a diffusion tensor is expressed quantitatively as fractional anisotropy (FA), which relects the propensity of water molecules within neurons to travel in an axial rather than radial direction.5,6,145,150 Nondamaged regions of the brain are highly organized into coherent ibers (Fig. 13-42A), which yield a high FA due to low radial diffusivity,8,131 whereas FA is reduced when radial diffusivity is increased, such as with traumatic axonal disruption or swollen and leaky axons.8,70,98,145 As such, decreased FA is a biomarker for DAI and other white matter lesions in the acute setting (see Fig. 13-42B). Swollen axons may recover (see Fig. 13-42C), but persistent decreased FA is predictive of long-term impairment.86,89,92,97,145

Over long periods of time ranging from months to years, as axons continue to degrade through wallerian degeneration, FA values can continue to gradually decrease.8 Speciic tracts that are variably involved include the genu (see Fig. 13-42) and splenium of the corpus callosum, with the latter involved in more severe injuries.116,145 White matter in the frontal and temporal lobes is also affected.145 FA values can show compensatory gradual increases in the internal capsule and centrum semiovale, which correlates with more favorable outcomes and likely relects neuroplasticity.125,145 Lower FA values correspond with greater degrees of axonal injury and greater disability.8,68,70,81

CONSIDERATIONS FOR PEDIATRIC TBI The pediatric population is much more susceptible to brain swelling following TBI than adults.68 This has been attributed to disproportionate increases in hyperemia, vasodilation, and increased blood volume. Leptomeningeal cysts are more common in pediatric TBI.73 These

CHAPTER 13 result from dural tears that act as one-way valves, causing herniation of arachnoid and pressure remodeling of bone, lytic lesions, or sutural widening.73 The bony manifestations of leptomeningeal cysts are sometimes referred to as growing fractures. Findings speciic to child abuse can be missed without an appropriate index of suspicion. The hallmark of abuse is the presence of multiple injuries without adequate explanation. Intracranial injuries among abused infants occur with a high incidence even in the absence of clinical signs. The infant skull is highly elastic,102 and intracranial injury can result without skull fracture. The threshold for head CT in suspected abuse should be very low. Children are prone to SDH from bridging vein disruption43,102 with repetitive shaking (Fig. 13-43). The impulsive forces also cause retinoschisis and retinal hemorrhage by indirect tugging on the retina from to-and-fro motions of the relatively dense lens and resultant ocular luid pressure waves.42,102 Hadley et al. introduced the term infant whiplash shake injury syndrome47 in 1989 to describe this constellation of indings, later renamed shaken baby syndrome.24 Shaking is also associated with a high frequency of injuries to the spinal cord,47,102 and routine MRI of the cervical spine should be performed in abused children with head injuries.102

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40. Ghajar J, Hariri RJ, Narayan RK, et al: Survey of critical care management of comatose, head-injured patients in the United States. Crit Care Med 23(3):560–567, 1995. 41. Greenberg J, Cohen WA, Cooper PR: The “hyperacute” extraaxial intracranial hematoma: Computed tomographic indings and clinical signiicance. Neurosurgery 17(1):48–56, 1985. 42. Greenwald M, Weiss A, Oesterle C, et al: Traumatic retinoschisis in battered babies. Ophthalmology 93(5):618–625, 1986. 43. Guthkelch A: Infantile subdural haematoma and its relationship to whiplash injuries. Br Med J 2(5759):430–431, 1971. 44. Gutman MB, Moulton RJ, Sullivan I, et al: Risk factors predicting operable intracranial hematomas in head injury. J Neurosurg 77(1):9– 14, 1992. 45. Guyot L, Kazmierczak C, Diaz F: Vascular injury in neurotrauma. Neurol Res 23(2–3):291–296, 2001. 46. Haacke EM, Mittal S, Wu Z, et al: Susceptibility-weighted imaging: Technical aspects and clinical applications, Part 1. AJNR Am J Neuroradiol 30(1):19–30, 2009. 47. Hadley M, Sonntag V, Rekate H, et al: The infant whiplash-shake injury syndrome: A clinical and pathological study. Neurosurgery 24(4),1989. 48. Hahn F, Gurney J: CT signs of central descending transtentorial herniation. AJNR Am J Neuroradiol 6(5):844–845, 1985. 49. Hähnel S, Stippich C, Weber I, et al: Prevalence of cerebral microhemorrhages in amateur boxers as detected by 3T MR imaging. AJNR Am J Neuroradiol 29(2):388–391, 2008. 50. Hammoud D, Wasserman B: Diffuse axonal injuries: Pathophysiology and imaging. Neuroimaging Clin N Am 12(2):205–216, 2002. 51. Hanstock C, Faden A, Bendall M, et al: Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue. Stroke 25(4):843– 848, 1994. 52. Hashimoto T, Nakamura N, Richard K, et al: Primary brain stem lesions caused by closed head injuries. Neurosurg Rev 16(4):291–298, 1993. 53. Haydel MJ, Preston CA, Mills TJ, et al: Indications for computed tomography in patients with minor head injury. NEJM 343(2):100–105, 2000. 54. Hesselink JR, Dowd CF, Healy ME, et al: MR imaging of brain contusions: A comparative study with CT. AJR Am J Roentgenol 150(5):1133–1142, 1988. 55. Holm L, Cassidy J, Carroll L, et al: Summary of the WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury. J Rehabil Med 37(3):137–141, 2005. 56. Holshouser BA, Tong KA, Ashwal S, et al: Spectroscopic imaging depicts diffuse axonal injury in children with traumatic brain injury. AJNR Am J Neuroradiol 26(5):1276–1285, 2005. 57. Hossmann K-A, Fischer M, Bockhorst K, et al: NMR imaging of the apparent diffusion coeficient (ADC) for the evaluation of metabolic suppression and recovery after prolonged cerebral ischemia. J Cereb Blood Flow Metab 14(5):723–731, 1994. 58. Huisman T, Gregory S, Hergan K, et al: Diffusion-weighted imaging for the evaluation of diffuse axonal injury in closed head injury. J Comput Assist Tomogr 27(1):5–11, 2003. 59. Hunter JV, Thornton RJ, Wang ZJ, et al: Late proton MR spectroscopy in children after traumatic brain injury: Correlation with cognitive outcomes. AJNR Am J Neuroradiol 26(3):482–488, 2005. 60. Ingebrigtsen T, Romner B, Kock-Jensen C: Scandinavian guidelines for initial management of minimal, mild, and moderate head injuries. J Trauma 48(4):760–766, 2000. 61. Ishikawa M, Kikuchi H, Fujisawa I, et al: Tonsillar herniation on magnetic resonance imaging. Neurosurgery 22(1 Pt 1):77–81, 1988. 62. Jeret JS, Mandell M, Anziska B, et al: Clinical predictors of abnormality disclosed by computed tomography after mild head trauma. Neurosurgery 32(1):9–16, 1993. 63. Johnson P, Eckard D, Chason D, et al: Imaging of acquired cerebral herniations. Neuroimaging Clin N Am 12(2):217–228, 2002. 64. Jones TR, Kaplan RT, Lane B, et al: Single– versus multi–detector row CT of the brain: Quality assessment. Radiology 219(3):750–755, 2001.

65. Juul N, Duch B, Rasmussen M: Clinical management of patients with head injury. Curr Anaesth Crit Care 20(3):132–137, 2009. 66. Kao M-C: Sedimentation level in chronic subdural hematoma visible on computerized tomography. J Neurosurg 58(2):246–251, 1983. 67. Kelly A, Zimmerman R, Snow R, et al: Head trauma: Comparison of MR and CT—Experience in 100 patients. AJNR Am J Neuroradiol 9(4):699–708, 1988. 68. Kim J, Gean A: Imaging for the diagnosis and management of traumatic brain injury. Neurother 8(1):39–53, 2011. 69. Kostanian V, Choi J, Liker M, et al: Computed tomographic characteristics of chronic subdural hematomas. Neurosurg Clin N Am 11(3):479–489, 2000. 70. Kubal WS: Updated imaging of traumatic brain injury. Radiol Clin North Am 50(1):15–41, 2012. 71. Kwee RM, Kwee TC: Virchow-Robin spaces at MR imaging. Radiographics 27(4):1071–1086, 2007. 72. Langlois JA, Rutland-Brown W, Wald MM: The epidemiology and impact of traumatic brain injury: A brief overview. J Head Trauma Rehabil 21(5):375–378, 2006. 73. Le TH, Gean AD: Neuroimaging of traumatic brain injury. Mt Sinai J Med 76(2):145–162, 2009. 74. Lee KS, Bae WK, Bae HG, et al: The computed tomographic attenuation and the age of subdural hematomas. J Korean Med Sci 12(4):353–359, 1997. 75. Lee E-J, Hung Y-C, Wang L-C, et al: Factors inluencing the functional outcome of patients with acute epidural hematomas: Analysis of 200 patients undergoing surgery. J Trauma 45(5):946–952, 1998. 76. Lee B, Newberg A: Neuroimaging in traumatic brain imaging. NeuroRx 2(2):372–383, 2005. 77. Lee H, Wintermark M, Gean AD, et al: Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 25(9):1049–1056, 2008. 78. Lloyd M, Kimber P, Burrows E: Post-traumatic cerebrospinal luid rhinorrhoea: Modern high-deinition computed tomography is all that is required for the effective demonstration of the site of leakage. Clin Radiol 49(2):100–103, 1994. 79. Lobato RD, Sarabia R, Cordobes F, et al: Posttraumatic cerebral hemispheric swelling. J Neurosurg 68(3):417–423, 1988. 80. Maas A, Hukkelhoven C, Marshall L, et al: Prediction of outcome in traumatic brain injury with computed tomographic characteristics: A comparison between the computed tomographic classiication and combinations of computed tomographic predictors. Neurosurgery 57(6):1173–1182, 2005. 81. Maas AIR, Stocchetti N, Bullock R: Moderate and severe traumatic brain injury in adults. Lancet Neurol 7(8):728–741, 2008. 82. Macpherson B, MacPherson P, Jennett B: CT evidence of intracranial contusion and haematoma in relation to the presence, site and type of skull fracture. Clin Radiol 42(5):321–326, 1990. 83. Mannion RJ, Cross J, Bradley P, et al: Mechanism-based MRI classiication of traumatic brainstem injury and its relationship to outcome. J Neurotrauma 24(1):128–135, 2007. 84. Marmarou A, Signoretti S, Fatouros P, et al: Mitochondrial injury measured by proton magnetic resonance spectroscopy in severe head trauma patients. Acta Neurochir Suppl 95:149–151, 2005. 85. Marmarou A, Signoretti S, Fatouros PP, et al: Predominance of cellular edema in traumatic brain swelling in patients with severe head injuries. J Neurosurg 104(5):720–730, 2006. 86. Marquez de la Plata CD, Yang FG, Wang JY, et al: Diffusion tensor imaging biomarkers for traumatic axonal injury: Analysis of three analytic methods. J Int Neuropsychol Soc 17(01):24–35, 2011. 87. Marshall LF, Marshall SB, Klauber MR, et al: A new classiication of head injury based on computerized tomography. Spec Suppl 75(1s):S14–S20, 1991. 88. Marshall L, Marshall S, Klauber M, et al: The diagnosis of head injury requires a classiication based on computed axial tomography. J Neurotrauma 9(Suppl 1):S287–S292, 1992. 89. Matsushita M, Hosoda K, Naitoh Y, et al: Utility of diffusion tensor imaging in the acute stage of mild to moderate traumatic brain injury

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113. Rivas J, Lobato R, Sarabia R, et al: Extradural hematoma: Analysis of factors inluencing the courses of 161 patients. Neurosurgery 23(1):44– 51, 1988. 114. Rothfus W, Goldberg A, Tabas J, et al: Callosomarginal infarction secondary to transfalcial herniation. AJNR Am J Neuroradiol 8(6):1073– 1076, 1987. 115. Rubin Y, Cecil K, Wehrli S, et al: High-resolution 1H NMR spectroscopy following experimental brain trauma. J Neurotrauma 14(7):441–449, 1997. 116. Rutgers DR, Fillard P, Paradot G, et al: Diffusion tensor imaging characteristics of the corpus callosum in mild, moderate, and severe traumatic brain injury. AJNR Am J Neuroradiol 29(9):1730–1735, 2008. 117. Schaefer PW, Huisman TAGM, Sorensen AG, et al: Diffusion-weighted MR imaging in closed head injury: High correlation with initial Glasgow Coma Scale score and score on Modiied Rankin Scale at discharge. Radiology 233(1):58–66, 2004. 118. Scheid R, Preul C, Gruber O, et al: Diffuse axonal injury associated with chronic traumatic brain injury: Evidence from T2*-weighted gradientecho imaging at 3 T. AJNR Am J Neuroradiol 24(6):1049–1056, 2003. 119. Seelig JM, Becker DP, Miller JD, et al: Traumatic acute subdural hematoma: Major mortality reduction in comatose patients treated within four hours. NEJM 304(25):1511–1518, 1981. 120. Sehgal V, Delproposto Z, Haacke EM, et al: Clinical applications of neuroimaging with susceptibility-weighted imaging. J Magn Reson Imaging 22(4):439–450, 2005. 121. Servadei F, Faccani G, Roccella P, et al: Asymptomatic extradural haematomas. Results of a multicenter study of 158 cases in minor head injury. Acta Neurochir (Wien) 96(1–2):39–45, 1989. 122. Servadei F, Murray GD, Teasdale GM, et al: Traumatic subarachnoid hemorrhage: Demographic and clinical study of 750 patients from the European Brain Injury Consortium survey of head injuries. Neurosurgery 50(2):261–269, 2002. 123. Shackford S, Wald S, Ross S, et al: The clinical utility of computed tomographic scanning and neurologic examination in the management of patients with minor head injuries. J Trauma 33(3):385–394, 1992. 124. Shutter L, Tong KA, Lee A, et al: Prognostic role of proton magnetic resonance spectroscopy in acute traumatic brain injury. J Head Trauma Rehabil 21(4):334–349, 2006. 125. Sidaros A, Engberg AW, Sidaros K, et al: Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: A longitudinal study, 2008. 126. Sifri ZC, Livingston DH, Lavery RF, et al: Value of repeat cranial computed axial tomography scanning in patients with minimal head injury. Am J Surg 187(3):338–342, 2004. 127. Sigmund GA, Tong KA, Nickerson JP, et al: Multimodality comparison of neuroimaging in pediatric traumatic brain injury. Pediatr Neurol 36(4):217–226, 2007. 128. Sinson G, Bagley LJ, Cecil KM, et al: Magnetization transfer imaging and proton MR spectroscopy in the evaluation of axonal injury: Correlation with clinical outcome after traumatic brain injury. AJNR Am J Neuroradiol 22(1):143–151, 2001. 129. Smith DH, Meaney DF, Shull WH: Diffuse axonal injury in head trauma. J Head Trauma Rehabil 18(4):307–316, 2003. 130. Solomon GS, Haase RF: Biopsychosocial characteristics and neurocognitive test performance in National Football League players: An initial assessment. Arch Clin Neuropsychol 23(5):563–577, 2008. 131. Song S-K, Sun S-W, Ramsbottom MJ, et al: Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17(3):1429–1436, 2002. 132. Spitz G, Maller JJ, Ng A, et al: Detecting lesions after traumatic brain injury using susceptibility weighted imaging: A comparison with luid-attenuated inversion recovery and correlation with clinical outcome. J Neurotrauma 30(24):2038–2050, 2013. 133. Stein SC, Chen X-H, Sinson GP, et al: Intravascular coagulation: A major secondary insult in nonfatal traumatic brain injury. J Neurosurg 97(6):1373–1377, 2002.

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14 Spinal Cord Injury David Dreizin and Daniel Mascarenhas

INTRODUCTION More than 10,000 spinal cord injuries are diagnosed each year in the United States, with over half involving the cervical spinal cord.2,7,69 Multidetector computed tomography (CT) is recommended by the American College of Radiology as the irst-line screening exam for any patient for whom spine injury cannot be excluded on clinical grounds alone.24 Coronal and sagittal spine reformats are also commonly incorporated into whole-body CT protocols for severe blunt trauma.15,14 CT is more cost-effective for initial cervical spine screening and appears to have a greater risk-beneit proile than plain radiography despite an order of magnitude greater radiation dose.14,63 This is largely due to the rate of missed injury on plain ilms, which can be higher than 50%.45 The use of magnetic resonance imaging (MRI) for spine clearance is controversial because CT is exquisitely sensitive for detection of unstable fracture patterns, and isolated signal abnormalities at MRI when bony relationships are normal are of questionable clinical signiicance.30 On the other hand, CT has little utility for directly evaluating the spinal cord and identifying extraaxial soft tissue pathology, owing to beam hardening from adjacent bony structures and poor contrast resolution.50 This chapter focuses primarily on issues pertaining to MRI of spinal cord injury (SCI). MRI is frequently used after trauma to evaluate patients with persistent neck tenderness (not explainable by CT), myelopathy, absence of clinical improvement, and for suspected epidural hematomas or traumatic disk herniations that compress the spinal cord. MRI is also useful for prognosticating severity of SCI, determining surgical approach, conirming suficient decompression of the spinal cord after surgery, evaluating progressive syrinx formation or other complications if recovery reverses in the chronic stage after injury, and guiding the duration of bracing in conservatively managed cases.6,16,35,50 Despite its widespread use, evidence supporting the use of MRI in the early acute setting for management purposes is not robust.6 The prognostic value of MRI for short- and long-term outcomes after SCI is relatively well established.21,22,51,55,59

SPINAL CORD INJURY MECHANISMS Most fractures in both adult and pediatric patients with spinal cord injuries occur in the highly mobile cervical spine. These usually result from impulsive loading (i.e., whiplash).14 In adults the fulcrum of the cervical spine is at C5-C6, and unstable hyperlexion injuries tend to cluster around this motion segment (Fig. 14-1). Hyperextension injuries have a higher center of rotation, often resulting from deceleration motor vehicle collisions with facial impact or in the elderly with face-planting after trivial falls. In up to one third of patients,11,71 SCI occurs without skeletal or ligamentous disruption appreciable on CT. This has come to be called

by the terms spinal cord injury without radiographic abnormality (SCIWORA) in pediatric patients47 and spinal cord injury without radiographic evidence of trauma (SCIWORET) in adults—in the latter to account for nontraumatic abnormalities usually related to spondylosis.4,61 In adults, SCI in this setting commonly manifests as central cord syndrome, in which the upper extremities are disproportionately affected (Fig. 14-2). Young children have highly elastic spinal columns that can recoil back to normal alignment and exhibit no evidence of bone or discoligamentous injury despite severe SCIs, including transection. Some athletes involved in contact sports may be predisposed to “stinger syndrome” and “spinal cord concussion,” in which myelopathic symptoms are typically minor and resolve after short periods.32,53,62,64,72 Patients with congenitally narrowed spinal canals appear to be predisposed to SCI, but the positive predictive value of various measurement parameters of spinal stenosis appears to be limited.29,49,65 Extraneural indings that can beneit from decompression (e.g., traumatic disk herniations, epidural hematomas) are more common in older patients, especially in the setting of fused spine from ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, chronic spondylotic changes, or prior spinal surgery16,71 (Fig. 14-3). In those older than 60 years, profound residual deicits, morbidity, and high mortality are common after SCI.13,61

MRI PROTOCOL CONSIDERATIONS 1.5-tesla (T) and 3-T protocols vary considerably from institution to institution. Sagittal T2-weighted imaging or short tau inversion recovery (STIR) images are acquired with near ubiquity and are by far the most important from a prognostic standpoint because of their ability to visualize both the presence of spinal cord hemorrhage and the craniocaudal extent of edema.6 Sagittal proton density images can very clearly depict disruptions in the continuity of discoligamentous structures, but the added value of this sequence to T2-weighted imaging and STIR, which are also used for this purpose, remains unproven. Findings of ligamentous injury in the thoracolumbar and cervical spine at STIR have been shown to correlate well with indings at surgery,26,37 and STIR has the added beneit of identifying marrow edema and bone bruising due to fat suppression50,68 (Fig. 14-4). Signal patterns useful for prognostication have not been established with axial images.6,16 Axial gradient echo (GRE) images are highly sensitive to susceptibility artifact from blood product and can depict areas of spinal cord hemorrhage with greater conspicuity than T2 (see Fig. 14-1B). Nevertheless, the added prognostic value of GRE remains unknown, and GRE is incorporated in only about one fourth of protocols in published studies.6 Axial T2-weighted images have not been shown to have prognostic value but can identify clinically relevant lesions such as disk herniation and spinal cord compression that may

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*

A

C

B

D FIG 14-1 This 30-year-old man sustained a teardrop fracture at C5-C6 after a fall and presented with complete motor and sensory loss. A, Sagittal T2-weighted imaging shows high signal, in keeping with cord edema from C3-C7 (cranial and caudal extent demarcated by long arrows). Foci of low signal intensity at C5 and C6 are consistent with intramedullary hemorrhage (open arrow). The anterior longitudinal ligament is stripped off the vertebral body of C6 (short arrow), which is retropulsed into the canal, compressing the spinal cord. There is extensive perivertebral hyperintensity, consistent with hemorrhage and edema (*). B, On axial GRE there is low signal intensity and blooming artifact at the level of hemorrhage (open arrows). C, On axial SWI there is low signal involving a greater proportion of the cord surface area, but the sequence is limited by motion. D, The full craniocaudal extent of cord hemorrhage (arrows) is well visualized on sagittal SWI.

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FIG 14-2 This 77-year-old man presented with central cord syndrome after a fall. Sagittal STIR image shows injured disk and ruptured anterior longitudinal ligament, resulting in anteriorly divergent widening at C4-C5 (short arrow). This abnormality was not appreciated at CT because of the extensive underlying degenerative changes. There is multilevel cord edema spanning C3-C6 (demarcated by long arrows). The patient underwent decompression and instrumented fusion.

alter management6 (see Fig. 14-3D). Rapid MRI sequences such as fast imaging employing steady-state acquisition (FIESTA) have gradient echo properties but do not accentuate blood breakdown products, owing to the use of balanced steady-state pulse sequences. These may decrease motion artifact but add little to conventional T2 sequences. The use of advanced sequences such as diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and susceptibility-weighted imaging (SWI) is not widespread, and data supporting their utility remains more controversial and less robust than in traumatic brain injury. There are diminishing returns from the acquisition of multiple sequences, and this must be weighed with considerations of safety, logistics, and resource allocation for patients who often require monitoring and anesthetic equipment and close oversight by healthcare personnel.50 Reducing the length of the total exam also increases the availability of the MR scanner.6

PROGNOSTIC SIGNIFICANCE OF MR FINDINGS AFTER SCI SCI severity occurs along a spectrum that is encapsulated in a simpliied four-pattern classiication system introduced in the late 1980s and modiied in the early 1990s.5,36 This has been shown in a handful of studies to correlate both with initial neurologic impairment (determined mostly using the American Spinal Cord Injury Association [ASIA] motor score) and degree of long-term improvement.21,22,51,55,59 Injuries are classiied as (1) nonedematous cord, (2) edema spanning a single vertebral level, (3) edema spanning multiple levels, and (4) mixed hemorrhage and edema. After “normal” nonedematous spinal cord, which is seen in 10% to 20% of patients with SCI, single-level

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edema has the best prognosis.6 Approximately one fourth of patients with single-level edema recover normal motor and sensory function (ASIA E). Patients with diffuse edema (Fig. 14-5) will almost invariably have permanent, at least partial, deicits with lower degrees of recovery. Those with diffuse edema who are initially ASIA A (complete motor and sensory deicit) will rarely show any meaningful improvement. Appreciable spinal cord hemorrhage is usually associated with complete motor and sensory loss and will rarely show meaningful improvement.6 Hemorrhage is rarely seen in the absence of edema. The term cord contusion has been variably used in the literature to refer to edema alone or to a speciic pattern of edema with central isointensity51 or to denote frank spinal cord hemorrhage (i.e., synonymous with hemorrhagic contusion).16 Prognosis from spinal cord hemorrhage appears to be slightly better when less than 50% of the spinal cord cross-sectional area is involved.27,52,62 The length of hemorrhage does not correlate with injury severity, likely because of the uniformly poor outcome in these patients regardless of whether single or multiple levels are involved (see Fig. 14-1D). For the same reason, complete cord transections are not included in prognostic grading scales6 (Fig. 14-6). Cord expansion is seen with more severe injury resulting from accumulation of both intracellular and interstitial luid above and below the injury.16 The utility of cord expansion as a predictor of outcome is controversial because the degree of enlargement can be limited by posttraumatic, degenerative, or congenital stenosis. Greater degrees of cord compression and canal compromise, best seen using axial T2 images, may correlate with worse prognosis.6,12,22,42,56 Spinal cord compression speciically by extraaxial hematoma may be another independent predictor of poor outcome,56 as is severity of prevertebral soft tissue injury, although this remains controversial.61

EVOLUTION OF SPINAL CORD INJURY—FINDINGS AT MRI Because of the small caliber of the cord and narrow space within the spinal canal, even small foci of hemorrhage within the spinal cord are associated with devastating neurologic outcomes and poor improvement over time. As such, SCI is not generally thought of in the discrete terms of primary and secondary injury that are used to characterize traumatic brain injury. The relationship between evolution of signal abnormality and time after injury has been studied, but major discrepancies between exam and electrophysiologic testing and MRI appearance are common.35 The ideal time interval for performing MRI after initial injury remains controversial. Surgical decompression within 24 hours for SCI patients and “very early” decompression within 12 hours for those with incomplete cervical SCIs has been recommended based on a worldwide survey of 971 spine surgeons.19 Although these recommendations would seem to support MRI in the early acute phase, it is not uniformly practiced at many centers. Bondurant et al. previously recommended that MRI be performed within 24 to 72 hours after trauma.5 Generally MRI plays an ancillary role to neurophysiologic testing, with additional prognostic information provided by injury morphology, as described in the previous section. As SCI transitions from acute to chronic phases, it is important to understand expected secondary morphologic changes resulting from injury evolution in the posttraumatic lesion area.35 Initially, edema with or without hemorrhage spreads cranially and caudally from the injury epicenter (Fig. 14-7). Shortly after injury, spinal cord hemorrhage is usually appreciated as low signal on T2 and edema as high signal.16,59 Extraneural blood may take only hours to develop high signal from methemoglobin (see Fig. 14-4B), whereas

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D FIG 14-3 Images of an 82-year-old man after a fall down stairs. Bony fusion of the vertebral bodies and posterior elements were present throughout the cervical spine. A, A coronally oriented fracture plane is seen traversing the posterior vertebral body of C4. An epidural hematoma is faintly visualized and suggested by loss of the normal dorsal epidural fat plane (solid arrow), which is preserved below C7 (open arrow). The epidural hematoma is well visualized on the sagittal PD (B) and STIR (C) images (solid white arrows). On the STIR image (C), long arrows point to injured disks at C5-C6 and C6-C7, and there is discontinuity of the ligamentum lavum at C6-C7, consistent with ligamentum lavum tear (open arrow). D, Axial T2-weighted imaging shows the epidural hematoma (open arrow) severely compressing the cord (solid arrow). This necessitated urgent surgical decompression.

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FIG 14-4 This 65-year-old man sustained a T12 burst fracture after a fall off a ladder. A, Sagittal STIR image shows marrow edema (*) and low-signal-intensity transverse fracture lines spanning the vertebral body. Edema is seen within the conus (open arrow). There is traumatic disk herniation at T12-L1, with an overlying epidural hematoma (arrows), which appears slightly hyperintense on the sagittal T1 image (B [arrows]).

Posttraumatic cysts are synonymous with syringomyelia or syrinx. These usually follow the signal intensity of cerebrospinal luid (CSF) and are well deined (Fig. 14-9). They result from rents in the ependymal lining of the central canal but are not covered by ependyma. Syringomyelia can sometimes be dificult to differentiate from hydromyelia (dilation of the central canal), and in such cases the term syringohydromyelia is used. Once a posttraumatic cyst has fully formed—usually within 1 year after injury—the cyst and spinal cord area are usually stable. In some instances posttraumatic cyst enlargement is observed (Fig. 14-10), but this does not necessarily correlate with symptomatology. Posttraumatic syrinx develops in 5% to 8% of SCI.17,35 Tethering and syrinx progression are suspected if the myotomes affected become more rostral. Surgical intervention may be warranted purely on the basis of MR indings if the rostral extent threatens to encroach on the brainstem.35

Concurrent Soft Tissue and Bony Injury in SCI

FIG 14-5 Hyperextension injury from trivial fall in a 50-year-old man, resulting in multilevel spinal cord edema spanning C3 and C4 (arrows). Clinically the patient had incomplete spinal cord injury, and he improved one ASIA score over time.

intraneurally this may take days to weeks, limiting the utility of T1-weighted imaging in the early acute phase after injury (Fig. 14-8). Sagittal T2-weighted and STIR images offer a global view of both the cord and discoligamentous structures along the full extent of the imaged spine.16,34 Acute injury is followed by a second subacute stage marked by regression of edema and hemorrhage,35 during which the transverse diameter of the cord may subside to normal or shrink. In the inal chronic stage, a posttraumatic cyst may form.35

Important soft tissue structures to evaluate at MRI in patients with SCI include the prevertebral musculature, anterior longitudinal ligament (ALL), intervertebral disk, and posterior longitudinal ligament (PLL) ventrally; and facet capsules, ligamentum lavum, interspinous ligament, supraspinous ligament, and paraspinal musculature dorsally.50 The craniocervical junction should be evaluated for integrity of the transverse and alar ligaments, which may be disrupted in craniocervical distraction injury. Normal appearances of these structures are shown in Figure 14-11. The ALL and facet capsules are the most important determinants of mechanical stability.14,69 The sine qua non of clinically important ligamentous injury is discontinuity of normal low ligamentous signal with intervening gap and high T2 signal indicative of hemorrhage and edema. These indings are best appreciated on sagittal STIR or T2-weighted imaging (see Figs. 14-1A, 14-2, 14-3C, 14-4A, 14-6A, 14-7A and B, and 14-8A). Despite its importance for determining stability, the ALL is among the most dificult structures to visualize because the inner layer is tightly adherent to the anterior

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FIG 14-6 A, Sagittal STIR image of a T4-T5 fracture-dislocation in a 64-year-old woman involved in a motor vehicle collision. The cord is transected at this level, and there is an intervening gap (open arrow). B, On sagittal T1-weighted image, dorsal epidural fat outlines the severed and displaced rostral and caudal ends of the spinal cord (open arrows).

cortex of the vertebral body and disk anulus. The sensitivity of MRI for cervical ALL injuries in patients with SCI ranges from 46% to 71%; for disk injury, approximately 93%; and for ligamentous injuries posterior to the vertebral bodies, from 67% to 95%.6,26,40,50 Posteriorly, sensitivity is lowest for the ligamentum lavum, the thin ligament bridging the laminae; however, this structure has a relatively minor role in determining spinal stability. Posteriorly, sensitivity is highest for supraspinous ligament tears.26 Muscle injury is managed conservatively but may help give a general picture of the extent of injury. SCI is more likely with severe injuries that cause retropulsion of bone into the canal or narrowing as the result of rotation and translation, which may crush the cord. MRI most precisely details degree of canal encroachment and spinal cord compression in these cases. MRI misses a substantial proportion of fractures, and as mentioned, CT is generally superior for this purpose. This is particularly the case for posterior elements where there is a paucity of cancellous bone.16 Evidence of concomitant facet capsular injury at MRI may call attention to a fracture. MRI provides superior deinition of extraaxial entities that may be causative of SCI and require urgent decompression, such as epidural hematoma and traumatic disk herniation. In the fused spine, MRI may reveal nondisplaced fractures or disk disruptions not readily apparent on CT (see Fig. 14-3). These injuries nevertheless have a high propensity for severe instability because the cranial and caudal portions of the fractured spine act as long lever arms. The threshold for obtaining MRI in these patients should be low. The bulky lowing osteophytes seen in diffuse idiopathic skeletal hyperostosis result in a propensity for injury planes traversing the vertebral body, whereas disk-level disruption is more common in ankylosing spondylitis.16,28,46 Dural tears are found in 7% to 28% of patients operated on for spinal injuries and are most common in lumbar burst fractures.8,33,44 One quarter of patients with lumbar burst fracture and neurologic deicit have dural tears requiring repair, and the great majority of

lumbar burst fractures with dural tear have a neurologic deicit.33 MRI can be used to identify dural tears acutely, although diagnosis with any conventional imaging modality is challenging.44 Dural tears are very dificult to visualize when rents are less than 1 cm in length.38 On T2 or STIR images, accumulations of CSF may be ill deined and blend into high interfacial and intermuscular signal within adjacent soft tissue. In more severe trauma, larger meningeal lacerations result in more spread-out collections. Indirect indings on MRI, including laminar fracture with gap, wide interpedicular distance, and marked canal narrowing, all increase the likelihood of dural tear.38 Isotropic sequences with heavy T2 weighting can have added beneit in making the diagnosis and identifying the origin and course of CSF istulae.38 CT myelography with intrathecal contrast may be an option in patients who cannot undergo MRI, but the procedure is often not tolerated in the trauma setting. The use of MR myelography has been described with intrathecal gadolinium administration, but the use of gadolinium for this purpose remains off label in both the United States and abroad.44 Dural tears are clinically important because they can act as foci for herniation of neural elements and nerve root entrapment,8,38 which may require decompression with a posterior surgical approach. Meningeal infection or inlammation may cause failure to heal and chronic posttraumatic meningocele.38 Chronically, neural structures may become entrapped in scar tissue.44 In brachial and (less commonly) in lumbosacral plexus traction injuries, nerve root avulsions are usually associated with meningeal tears and CSF collections. Reepithelialization of these collections results in formation of pseudomeningoceles54 (Fig. 14-12). In the cervical spine these are virtually pathognomonic for nerve root avulsion.54

Canal Stenosis as a Predictor of SCI A number of anatomic characteristics may predispose individuals to SCI after trauma.1,18,20,25,60,64-66 The most widely evaluated radiographic measurement parameter of canal stenosis is the Torg-Pavlov ratio

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C FIG 14-7 A, Sagittal STIR image of a 53-year-old woman with hyperlexion injury after fall, showing spinal cord edema spanning C3-C5 (arrows). There is interspinous widening at C5-C6 (*), with mild focal kyphosis at this level. B, Parasagittal STIR image shows C5-C6 facet subluxation. The patient underwent decompressive laminectomy and anterior corpectomy, diskectomy, and fusion (ACDF). C, On follow-up MRI several days later there is evolution of the SCI, with increased craniocaudal extent of spinal cord edema and expansion of the spinal cord.

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D FIG 14-8 This 50-year-old man had an unstable burst fracture at C4 and quadriplegia. A, Sagittal T2-weighted image shows disk disruption and stripping of the anterior and posterior longitudinal ligaments (open arrows) at C4-C5. There is spinal cord edema from C2-C6, and a focus of low signal intensity at C4-C5 consistent with hemorrhage (solid arrow). B, On sagittal SWI the hemorrhage appears more extensive (arrow). C, On the corresponding sagittal T1-weighted image the hemorrhage is not appreciated. D, On follow-up scan 1 week later, there is high signal within the cord on T1 (arrow), corresponding with the area of low signal previously identiied on sagittal T2. This relects evolution of blood products and accumulation of methemoglobin in the subacute phase of SCI.

CHAPTER 14

FIG 14-9 This 37-year-old woman presented with central cord syndrome after a fall 2 years prior to this study. On this sagittal STIR image, there is atrophic thinning of the cord (solid arrows) and a focus of syrinx at C4-5 (open arrow).

Spinal Cord Injury

FIG 14-10 A 56-year-old man with remote craniocervical injury after a motor vehicle collision. The patient developed progressive lower extremity weakness and was found to have a long segment of syringohydromyelia spanning C5-T9, with only a thin residual rim of spinal cord along the periphery (arrow). This was surgically treated with laminectomy and drainage by marsupialization.

O D O

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B FIG 14-11 Normal spinal column in a 20-year-old man after a motor vehicle collision. A, Sagittal T2-weighted image of the cervical spine shows intact anterior longitudinal ligament (black open arrow), posterior longitudinal ligament (white open arrow), ligamentum lavum (thin white arrow), interspinous ligaments (*), and supraspinous ligament (thin black arrow). B, Axial T2 image through the craniocervical junction shows intact alar ligaments (arrow), which fan out from the dens (D) to the occipital condyles (O). Continued

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D FIG 14-11, cont’d C, Axial T2 also shows an intact transverse ligament, which extends from the medial aspect of one lateral mass of the atlas (A) to the other, completing the osseoligamentous ring around the dens (D), formed anteriorly by the anterior arch of the atlas. D, In the parasagittal T2-weighted image, normal alignment of the facets and normal signal within the facet capsules are seen.

risk of SCI after minor trauma.1 The canal diameter at MRI is measured from the outer dorsal and ventral margins of the subarachnoid space (Fig. 14-13). The clinical implications of a narrow spinal canal in asymptomatic patients remain unclear.

ADVANCED IMAGING TECHNIQUES

FIG 14-12 A remote motor vehicle collision caused right brachial plexus injury with nerve root avulsion in this 53-year-old patient. A chronic posttraumatic pseudomeningocele is seen at C6-C7, extending through the right neural foramen at this level (arrow).

(TPR),66,65 derived by dividing the narrowest midvertebral sagittal canal diameter in the cervical spine by the sagittal diameter of the corresponding vertebral body at the same level. The TPR is a plain radiographic parameter with limited positive predictive value, partly attributable to variability in vertebral body dimensions, a factor not directly dependent on canal diameter.3,29,31,49,65 The TPR also does not take into account spondylotic changes occurring at the disk level. Recently, measurement parameters have been reevaluated with MRI. A disk-level canal diameter of less than 8 mm is associated with a high

Advanced techniques will be necessary to explain variations in improvement between patients with similar imaging indings on conventional MRIs or for monitoring regeneration.6,10,35,39,48 Reproducibility and re-test reliability is critical for following injury evolution longitudinally, especially for DTI.41,43 At present, advanced sequences that are gaining widespread use for traumatic brain injury, including DWI, SWI, and DTI, have limited clinical applicability in the spinal cord. These sequences are limited by motion artifacts, the narrow caliber of the spinal cord, and susceptibility and ield inhomogeneity resulting from adjacent bony structures and lungs.39,48,70 Conventional MR sequences detect gross morphologic abnormalities but do not have the ability to resolve the integrity of long white matter tracts. DWI has the potential to detect early pathologic changes not apparent on conventional sequences; however, the small body of literature evaluating the utility of DWI at 1.5 T in the early acute setting shows similar sensitivity to T2, with no added beneit.48,58,67 SWI may identify smaller amounts of hemorrhage than GRE, but it is even more prone to motion disturbances (see Fig. 14-1B and C) and can result in artifactual microhemorrhage. SWI has been shown to be more sensitive for hemorrhage than T2, although the study lacked a reference standard.70 DTI quantiies the diffusion of water molecules along tensors parallel and perpendicular to axonal tracts and may eventually be used in the clinical setting to track axons and distinguish pathology involving white and gray matter.43,57 To date, only a few small studies have shown a correlation between decreased fractional anisotropy with DTI and clinical SCI severity,9,43 but iber tracking suitable for clinical use will require substantial technical improvements.39 The cervical spine becomes most stenotic with extension and is narrowest at the C4 level.25 Dynamic imaging may be useful for evaluation of critical stenosis during hyperextension or

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FIG 14-13 This 60-year-old man was hit in the head by falling scaffolding and presented clinically with an incomplete spinal cord injury. A, Sagittal CT shows ossiication of the posterior longitudinal ligament from C2-C3 to C4 (arrow), with resultant severe narrowing of the spinal canal. B, Sagittal T2-weighted image showed no abnormal signal in the cord despite a minimum disk-level canal diameter of only 5 mm (doubleheaded arrow).

hyperlexion after SCI, as well as the effect on the cord and nerve roots; however, motorized or stepwise positioning devices are still largely experimental.23

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44. Muñoz A, Mateo I, Lorenzo V, et al: MR cisternography/myelography of post-traumatic spinal CSF istulae and meningeal lesions in small animals. Acta Radiol 54(5):569–575, 2013. 45. Nuñez D, Jr, Ahmad A, Coin C, et al: Clearing the cervical spine in multiple trauma victims: A time-effective protocol using helical computed tomography. Emerg Radiol 1(6):273–278, 1994. 46. Paley D, Schwartz M, Cooper P, et al: Fractures of the spine in diffuse idiopathic skeletal hyperostosis. Clin Orthop Relat Res 267:22–32, 1991. 47. Pang D, Wilberger JJ: Spinal cord injury without radiographic abnormalities in children. J Neurosurg 57(1):114–129, 1982. 48. Pouw MH, van der Vliet AM, van Kampen A, et al: Diffusion-weighted MR imaging within 24 hours post-injury after traumatic spinal cord injury: A qualitative meta-analysis between T2-weighted imaging and diffusion-weighted MR imaging in 18 patients. Spinal Cord 50(6):426– 431, 2012. 49. Presciutti SM, DeLuca P, Marchetto P, et al: Mean subaxial space available for the cord index as a novel method of measuring cervical spine geometry to predict the chronic stinger syndrome in American football players. J Neurosurg Spine 11(3):264–271, 2009. 50. Provenzale J: MR imaging of spinal trauma. Emerg Radiol 13(6):289–297, 2007. 51. Ramón S, Domínguez R, Ramírez L, et al: Clinical and magnetic resonance imaging correlation in acute spinal cord injury. Spinal Cord 35(10):664–673, 1997. 52. Regenbogen V, Rogers L, Atlas S, et al: Cervical spinal cord injuries in patients with cervical spondylosis. AJR Am J Roentgenol 146(2):277–284, 1986. 53. Rozzelle CJ, Aarabi B, Dhall SS, et al: Spinal cord injury without radiographic abnormality (SCIWORA). Neurosurgery 72:227–233, 2013. 10.1227/NEU.0b013e3182770ebc. 54. Sasaka KK, Phisitkul P, Boyd JL, et al: Lumbosacral nerve root avulsions: MR imaging demonstration of acute abnormalities. Am J Neuroradiol 27(9):1944–1946, 2006. 55. Schaefer D, Flanders A, Osterholm J, et al: Prognostic signiicance of magnetic resonance imaging in the acute phase of cervical spine injury. J Neurosurg 76(2):218–223, 1992. 56. Selden NR, Quint DJ, Patel N, et al: Emergency magnetic resonance imaging of cervical spinal cord injuries: Clinical correlation and prognosis. Neurosurgery 44(4):785–792, 1999. 57. Shanmuganathan K, Gullapalli RP, Zhuo J, et al: Diffusion tensor MR imaging in cervical spine trauma. Am J Neuroradiol 29(4):655–659, 2008. 58. Shen H, Tang Y, Huang L, et al: Applications of diffusion-weighted MRI in thoracic spinal cord injury without radiographic abnormality. Int Orthop 31(3):375–383, 2007. 59. Shimada K, Tokioka T: Sequential MR studies of cervical cord injury: Correlation with neurological damage and clinical outcome. Spinal Cord 37(6):410–415, 1999. 60. Song K-J, Choi B-W, Kim S-J, et al: The relationship between spinal stenosis and neurological outcome in traumatic cervical spine injury: An analysis using Pavlov’s ratio, spinal cord area, and spinal canal area. Clin Orthop Surg 1(1):11–18, 2009. 61. Sun L, Shen Y, Li Y: Quantitative magnetic resonance imaging analysis correlates with surgical outcome of cervical spinal cord injury without radiologic evidence of trauma. Spinal Cord 52(7):541–546, 2014. 62. Tewari MK, Gifti DS, Singh P, et al: Diagnosis and prognostication of adult spinal cord injury without radiographic abnormality using magnetic resonance imaging: Analysis of 40 patients. Surg Neurol 63(3):204–209, 2005. 63. Theocharopoulos N, Chatzakis G, Damilakis J: Is radiography justiied for the evaluation of patients presenting with cervical spine trauma? Med Phys 36(10):4461–4470, 2009. 64. Torg JS, Corcoran TA, Thibault LE, et al: Cervical cord neurapraxia: Classiication, pathomechanics, morbidity, and management guidelines. J Neurosurg 87(6):843–850, 1997.

CHAPTER 14 65. Torg J, Naranja R, Jr, Pavlov H, et al: The relationship of developmental narrowing of the cervical spinal canal to reversible and irreversible injury of the cervical spinal cord in football players. J Bone Joint Surg Am 78(9):1308–1314, 1996. 66. Torg J, Pavlov H, Genuario S, et al: Neurapraxia of the cervical spinal cord with transient quadriplegia. J Bone Joint Surg Am 68(9):1354–1370, 1986. 67. Tsuchiya K, Fujikawa A, Honya K, et al: Value of diffusion-weighted MR imaging in acute cervical cord injury as a predictor of outcome. Neuroradiology 48(11):803–808, 2006. 68. Utz M, Khan S, O’Connor D, et al: MDCT and MRI evaluation of cervical spine trauma. Insights Imaging 5(1):67–75, 2014.

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69. Vaccaro AR, Hulbert RJ, Patel AA, et al: The subaxial cervical spine injury classiication system: A novel approach to recognize the importance of morphology, neurology, and integrity of the discoligamentous complex. Spine 32(21):2365–2374, 2007. 10.1097/ BRS.0b013e3181557b92. 70. Wang M, Dai Y, Han Y, et al: Susceptibility weighted imaging in detecting hemorrhage in acute cervical spinal cord injury. Magn Reson Imaging 29(3):365–373, 2011. 71. Yucesoy K, Yuksel KZ: SCIWORA in the MRI era. Clin Neurol Neurosurg 110(5):429–433, 2008. 72. Zwimpfer T, Bernstein M: Spinal cord concussion. J Neurosurg 72(6):894–900, 1990.

15 Neurodegenerative Disorders Federica Agosta, Francesca Caso, and Massimo Filippi

It is often clinically dificult to differentiate among the various neurodegenerative disorders such as dementias, hydrocephalus, and movement disorders, and even between pathologic and normal aging. In recent years, more speciic and sensitive neuroimaging criteria have evolved to more accurately establish the correct diagnosis in these disorders. Magnetic resonance imaging (MRI), with its ability to image both the structure and function of the living brain, is an invaluable tool. In general, the tendency is to move away from simply excluding other (brain) diseases toward inding speciic pointers to a diagnosis in the ield of neurodegenerative disorders. The contribution of MRI to the evaluation of neurodegenerative disorders will no doubt increase as the population ages and as new pharmacologic and surgical therapies for these disorders develop.

NORMAL AGING Normal aging of the brain can be deined as a set of structural, metabolic and functional abnormalities of both the gray (GM) and white (WM) matter. Incidental WM hyperintensities (WMHs) can be seen on computed tomography (CT) scans, but they are better visualized on proton density–weighted, T2-weighted, and luidattenuated inversion recovery (FLAIR) MRIs of the brain in about 30% of healthy subjects older than 60 years.128 Their prevalence rises steadily with increasing age. Age-related WMHs are usually located in the deep and subcortical WM and around the ventricles (Fig. 15-1).45,63 Brainstem lesions are less common. They have different features on MRI scans, the most typical of which are punctate hyperintensities, periventricular caps and halos, and large lesions (which can be conluent).45,63 The severity of normally occurring brain volume loss is variable, ranging from minimal to moderately severe. Age-related changes in brain volume are apparent in both postmortem and in vivo MRI studies (see Fig. 15-1).8,117 Pathologic studies have found that brain weight peaks by the middle to late teens and declines slowly (0.1%0.2% a year) until the age of 60 to 70, after which losses accelerate.117 Longitudinal MRI studies report that rates of global atrophy in healthy people increase gradually with age from an annual rate of 0.2% a year at age 30 to 50 to 0.3% to 0.5% at age 70 to 80.8 GM volume starts to decrease early in life (at the end of the irst decade), whereas WM volume starts to decrease at the fourth decade. On average, GM volume loss is greater in the cortex than in subcortical structures. Age-related cortical density decrease seems to follow a gradient, with greatest and earliest changes occurring in association areas, especially those of the prefrontal cortex.116 However, recent MRI studies have described, in addition to an age-related atrophy of associative cortices, a widespread age-related thinning of a large portion of the cortical ribbon, including several primary areas, which were previously considered to be spared by aging.116 Cerebral WM also exhibits various types of degenerative

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changes. Although WM loss starts later in life than that of GM, the rate of such a tissue loss seems then to be faster.103 WM age-related loss is more pronounced in subcortical regions (with a preferential involvement of the frontal lobe). Diffusion tensor (DT) MRI studies conirmed reduced WM integrity in elderly people, especially in the frontal lobes.140

DEMENTIA Dementia can be caused by myriad pathologic processes, including anatomic (e.g., abscess, tumor, subdural hematoma, posttraumatic encephalomalacia, diffuse axonal injury), metabolic (e.g., electrolyte imbalance, nutritional deiciency, endocrinopathy, toxic exposure, medications), psychiatric (depression), degenerative (e.g., Alzheimer’s disease [AD], Parkinson’s disease [PD], frontotemporal dementia [FTD], dementia with Lewy bodies [DLB]), vascular (e.g., cerebral infarction, Binswanger’s disease, CADASIL), infectious/inlammatory (e.g., chronic meningitis, vasculitis, prion disease, Hashimoto’s encephalopathy), demyelinating disease (e.g., multiple sclerosis), and paraneoplastic phenomena (e.g., limbic encephalitis). It is often not possible to establish the cause by clinical examination alone. Neuroimaging assessment, traditionally and currently, is used to rule out the presence of some treatable causes of dementia. Current imaging techniques allow us to determine whether indings are consistent with or even typical of a certain diagnosis.47

Alzheimer’s Disease AD, the most common dementing disorder in older adults,90 has been recognized as one of the most signiicant health problems of the 20th and 21st centuries. AD is estimated to affect 10% of people older than 65 years and 50% of individuals older than 85 years.107 Two abnormal protein aggregates characterize AD pathology: neuritic plaques and neuroibrillary tangles (NFTs).107 Neuritic plaques are extracellular deposits and consist of a dense central core of amyloid β ibrils with inlammatory cells and dystrophic neurites in its periphery. The second major proteinopathy in AD is aggregated tau, which consists of intraneuronal polymers primarily composed of hyperphosphorylated tau in the form of NFTs.107 In typical late-onset (arbitrarily deined as age at onset > 65 years) AD, the medial temporal lobes (MTL), especially the hippocampus and entorhinal cortex, are among the earliest sites of pathologic involvement11,124 (Fig. 15-2). MTL atrophy in the presence of memory loss is now one of the supportive biomarkers to make a diagnosis of AD proposed by the new diagnostic criteria.38,39,90 Other severely affected regions include the posterior portion of the cingulate gyrus and the precuneus on the medial surface (see Fig. 15-2), and the parietal, posterior superior temporal, and frontal regions on the lateral cerebral surfaces.48,124

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FIG 15-1 Axial proton density–weighted (A), T2-weighted (B), and FLAIR (C) MRIs of the brain from a 73-year-old healthy subject. Multiple hyperintense lesions suggestive of multifocal white matter pathology are visible. In C, CSF signal suppression allows better identiication of the lesions located in the periventricular and juxtacortical regions. D and E, Axial T1-weighted MRIs of the brain of an 82-year-old healthy subject. Enlargement of the cortical sulci and ventricular size is evident.

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FIG 15-2 Axial and coronal T1-weighted images from a typical case of Alzheimer’s disease (AD) showing prominent bilateral hippocampal and medial parietal atrophy (arrows). R, right; L, left.

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Structural MRI studies in mild cognitive impairment (MCI) have produced mixed results, both in terms of hippocampal and posterior cingulate and parietal involvement (absent, unilateral, or bilateral).5,14,26,137 The reasons for this variability may consist of different subject selection (i.e., diverse diagnostic inclusion criteria), small sample size (i.e., studies are not adequately powered to pick up differences even at the group level), and methodological differences. It is also worth noting that the largest source of variance in MCI studies is likely to be the intrinsic heterogeneity of the MCI population, because a relevant proportion of these subjects will not progress to dementia. MCI patients with predominant memory impairment (amnestic MCI), who are at increased risk of developing AD, have atrophy in a consistent set of cortical regions (the “cortical signature of AD”), including the MTL and temporoparietal cortex. Conversely, nonamnestic MCI shows a different pattern of atrophy characterized by relative sparing of the MTL and a regional involvement that is typically highly consistent with the observed clinical deicits. It should be emphasized that MTL atrophy may occur in other diseases as well; thus MTL atrophy alone lacks the speciicity to conidently exclude other dementias, in particular in patients at the MCI stage. Early-onset AD patients (i.e., onset of symptoms before age 65) showed less prominent MTL atrophy and greater involvement of the parietal, lateral temporal, and frontal regions compared to late-onset AD cases.22,50 A speciic visual rating scale has been designed, evaluating the posterior cingulate, precuneus, and superior parietal regions.77

The utility of such a scale has been assessed in pathologically proven (mostly early-onset) AD and frontotemporal lobar degeneration (FTLD) patients.80 Thirty percent of AD patients had posterior atrophy in the absence of abnormal MTL atrophy, whereas only 7% of the FTLD group had abnormal posterior atrophy scores and normal MTL.80 Adding the posterior atrophy to the MTL visual rating score improved discrimination of early-onset AD from normal controls and all AD from FTLD cases.80 Cerebral blood low (CBF) single-photon emission computed tomography (SPECT) and 18F-luorodeoxyglucose (FDG) positron emission tomography (PET) scans of typical AD patients demonstrate predominant hypoperfusion or reduced glucose metabolism in the temporoparietal regions, including the precuneus and the posterior cingulate cortex13 (Fig. 15-3). Functional frontal lobe involvement is also often reported in AD but usually in conjunction with and characteristically less severe than temporoparietal involvement.95 Overall hypoperfusion or hypometabolism in early-onset AD is much greater in magnitude and extent than that of late-onset AD, with similar dementia severity.108 The primary visual and sensorimotor cortices, cerebellum, thalamus, and basal ganglia are relatively spared in AD.95 FDG PET differentiates patients with MCI from healthy controls. Amnestic MCI typically shows regional hypometabolism consistent with AD, although the magnitude of reduction is milder than that in clinically probable AD cases.96,100 Longitudinal studies of patients with MCI found that if the baseline FDG PET scan suggests an AD-like

NC > FTD

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FIG 15-3 FDG-PET glucose metabolism. Normal controls (NC) > frontotemporal dementia (FTD) (upper left): hypometabolic regions in FTD patients compared with NC subjects. Alzheimer’s disease (AD) > FTD (upper right): hypometabolic regions in FTD patients compared with AD patients. NC > AD (lower left): hypometabolic regions in AD patients compared with NC subjects. FTD > AD (lower right): hypometabolic regions in AD patients compared with FTD patients. (From Kanda T, et al: Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies. Eur J Nucl Med Mol Imaging 35:2227–2234, 2008.)

CHAPTER 15 pattern, the probability of clinical progression within several years is extremely high.25,37

Frontotemporal Dementia FTD is the umbrella term encompassing a group of progressive proteinopathies that are heterogeneous with regard to etiology and neuropathology but share (1) atrophy of the frontal and/or temporal cortex as a morphologic feature and (2) deposition of abnormal ubiquitinated protein inclusions in the cytoplasm and nucleus of neuronal and glial cells as major pathologic constituents.110 FTD includes three clinical syndromes and three major underlying neuropathologic subtypes. The clinical syndromes, which are distinguished by the early and predominant symptoms, are: a behavioral dysexecutive disorder (behavioral variant [bv]FTD); a language disorder (primary progressive aphasia [PPA] variants); and a motor disorder such as amyotrophic lateral sclerosis (ALS), corticobasal syndrome (CBS), and progressive supranuclear palsy (PSP) syndrome. The neuropathologic

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subtypes are characterized by an abnormal accumulation of proteins82: microtubule-associated protein tau (MAPT), TAR DNA-binding protein (TDP) 43, and fused in sarcoma protein (FUS). FTLD-tau, FTLD-TDP, and FTLD-FUS represent 45%, 50%, and 5% of all FTLD cases, respectively, at postmortem examination. The designation of probable bvFTD by the revised diagnostic criteria111 restricts diagnosis to patients with demonstrable functional decline and typical neuroimaging indings, including frontal and/or temporal atrophy, and hypoperfusion or hypometabolism on PET or SPECT. Structural MRI studies showed that classic bvFTD presents with a combination of medial frontal, orbital-insular and anterior temporal cortical atrophy12,114,119 (Fig. 15-4). Such an atrophy pattern can be readily appreciated on coronal T1-weighted MRI scans (knifeedge atrophy) (see Fig. 15-4). The MTL is more affected anteriorly (i.e., the amygdala is more affected than the hippocampus and posterior hippocampus often appears normal). Nevertheless, the typical

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FIG 15-4 MRIs of patients with frontotemporal lobar degeneration syndromes. Top row, Axial and coronal T1-weighted images show a pattern of knife-edge frontal atrophy (arrows) in a patient with the behavioral variant of frontotemporal dementia (bvFTD). Middle row, Axial and coronal T1-weighted images show marked left frontal and perisylvian atrophy (arrows) in a patient with the nonluent variant of primary progressive aphasia (PPA). Bottom row, Major involvement of the anterior temporal lobes, with left predominance (arrows), is shown in a patient with the semantic variant of PPA. R, right; L, left.

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pattern is not necessarily present in all cases,75,92,105 particularly in patients with FTD and motor neuron disease, and the pattern of atrophy in bvFTD varies signiicantly across different cohorts.83,138 In some cases, bvFTD presents with remarkable atrophy of the right anterior temporal lobe and lesser involvement of the frontal regions.136 BvFTD is identiied on SPECT or PET scans by patterns of hypoperfusion or hypometabolism in frontal, insular, and anterior temporal regions that are typically quite asymmetrically centered into the frontolateral cortex69,71,94 (see Fig. 15-3). The regions mostly impaired are the medial frontal cortex, followed by the frontolateral and anterior temporal cortices. The regional pattern of predominantly frontal functional impairment in bvFTD, with relative sparing of posterior brain regions, usually allows a clear distinction between these patients and those with AD (see Fig. 15-3). In patients clinically diagnosed with PPA, who are then divided into clinical variants based on speciic speech and language features characteristic for each subtype, an “imaging-supported” diagnosis can be made if the expected pattern of focal atrophy on structural MRI scans or functional involvement on SPECT and FDG is found.59 Semantic variant PPA is associated with left anterior temporal atrophy (temporal pole) affecting the lateral and ventral temporal surfaces (see Fig. 15-4) as well as particularly the anterior hippocampus, amygdala, and fusiform gyrus.51,58,97,114 Semantic patients may have left hippocampal atrophy that is at least as severe as that seen in AD patients. In these patients, the hippocampal atrophy is predominantly located anteriorly, with relative preservation of the posterior hippocampal regions. As the disease progresses, the right temporal lobe becomes more involved.15 The nonluent PPA variant is associated with a characteristic pattern of left anterior perisylvian atrophy involving inferior, opercular, and insular portions of the frontal lobe58 (see Fig. 15-4). Motor and premotor regions and Broca’s area are also involved.58 Compared with controls, nonluent patients also have atrophy of the left hippocampus; however, it is less severe than that in AD patients.127 In the logopenic PPA variant, the pattern of atrophy primarily affects the left temporoparietal junction, including the left posterior superior and middle temporal gyri, as well as the inferior parietal lobule.57,58,93 Involvement of the left MTL is reported less consistently.58 Such a posterior temporoparietal pattern of atrophy chiely discriminates this syndrome from the other subtypes of PPA. In patients with semantic variant PPA, FDG PET studies showed asymmetric hypometabolism of the temporal lobes, more marked on the left side.36,99,109 A functional deicit of the left frontal opercular regions of the brain has been reported in nonluent variant PPA patients.100,101,109 In these cases, functional involvement of bilateral caudate nuclei and thalami was also described. Logopenic PPA patients usually show a pattern of left posterior temporoparietal hypometabolism on FDG PET scans.109

Dementia with Lewy Bodies DLB is the second most common type of degenerative dementia, accounting for 10% to 15% of cases.89 The core clinical features of DLB include luctuating attention, recurrent visual hallucinations, and spontaneous parkinsonism, as well as cognitive impairment characterized by deicits of attention, executive functions (e.g., planning deicits), and complex visual abilities.89 Memory deicits are not inevitably present, particularly in the early stages. Fluctuations of cognitive function over minutes, hours, or days are a core feature and affect mainly the level of arousal. DLB is characterized by nigrostriatal dopaminergic neurodegeneration, making dopaminergic imaging a potentially useful diagnostic tool

in the differential diagnosis with AD33 (Fig. 15-5). Low dopamine transporter uptake in the basal ganglia demonstrated by SPECT or PET has been included as a suggestive feature in the diagnostic criteria for DLB.89 On the contrary, its negativity does not exclude a clinical diagnosis of probable DLB; about 20% of probable DLB cases have a normal or inconclusive scan.102 Numerous studies reported predominant medial occipital cortex hypoperfusion or hypometabolism in DLB patients compared with AD, with a parietotemporal reduction common to both the diseases.3,67,95,96 Occipital lobe hypometabolism differentiated patients with DLB from AD in both clinically diagnosed96 and autopsy conirmed3,67,95 cohorts. No clear signature pattern of cerebral atrophy associated with DLB has been established so far. Similar to AD, a diffuse pattern of global GM atrophy including temporal, parietal, frontal, and insular cortices may occur in DLB,10,20,19 but at the same time a pattern of cortical GM loss restricted to frontal and parietal lobes has also been reported.7,139 On the whole, several volumetric studies have not found signiicant or disproportionate occipital atrophy in DLB.20,139 A relatively robust MR inding in DLB is that of a relative preservation of the MTL when compared with AD of similar clinical severity.19,21,139 This inding is supported by a prospective MRI study with pathologic veriication that found that MTL atrophy on MRI has a robust discriminatory power for distinguishing AD from DLB (sensitivity of 91% and speciicity of 94%).19 Thus a relative preservation of MTL structures on CT or MRI supports a diagnosis of DLB in the consensus diagnostic criteria.89 Subcortical structural alterations in terms of putamen atrophy have been described in some cases of DLB relative to AD,32 whereas no signiicant atrophy was detected in the caudate nucleus.4 A pattern of relatively focused atrophy of the midbrain, hypothalamus, and substantia innominata, with relative sparing of the hippocampus and temporoparietal cortex, has been found in DLB compared to AD cases.139 Whether these indings can contribute to an early diagnosis remains unknown. Furthermore a substantial overlap between DLB and AD with regard to atrophy in these regions detracts from the usefulness of these markers in individual cases.47

Creutzfeldt-Jakob Disease Creutzfeldt-Jakob disease (CJD) is a rare cause of rapidly progressive dementia and is one of several associated neurodegenerative illnesses whose pathogenesis is related to a small, nonviral, 30- to 35-kD proteinaceous infectious particle known as a prion.72 The loci of pathology involve the cerebral and cerebellar cortices as well as the basal ganglia, where neuronal loss, reactive astrocytosis, and formation of cytoplasmic vacuoles within the glia and neurons give the tissue a characteristic spongiform appearance on light microscopy.72 The clinical syndrome is typically one of rapid cognitive decline, often with psychosis and delirium.72 Motor abnormalities of cerebellar dysfunction can appear, and almost all patients show pronounced myoclonus before the inal phase of deepening unresponsiveness and coma. The time course of the disease from presentation until death is usually less than 1 year. Brain MRI, particularly diffusion-weighted imaging (DWI), has become increasingly important in the clinical diagnosis of prion diseases, both excluding nonprion forms of rapidly progressive dementias and demonstrating features considered typical of prion diseases. In sporadic CJD (sCJD), FLAIR and especially DWI sequences show hyperintensity in subcortical GM nuclei (striatum and thalamus) and cortical GM (so-called cortical ribboning)143 (Fig. 15-6). In addition, increased signal on T2 images is accompanied by restricted diffusion with signal hypointensity on apparent diffusion coeficient (ADC) maps (see Fig. 15-6), probably owing to speciic histopathologic

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D FIG 15-5 Dopaminergic imaging (123I iolupane dopamine transporter SPECT) in (A) a healthy control, (B) a patient with early Parkinson’s disease (PD; Hoehn and Yahr score I), (C) a patient with dementia with Lewy bodies (DLB), and (D) a patient with Alzheimer’s disease (AD). Normal control and AD patient show normal symmetric intense tracer uptake in striatum (both caudate nucleus and putamen). PD and DLB patients show bilaterally reduced uptake in the striatum, predominantly reduced in the putamen. Note the asymmetry (left reduced more than right) in PD patient (arrow in B). (From Kostic VS, et al: Parkinsonism. In Filippi M, Simon JH, editors: Imaging acute neurologic disease: A symptom-based approach. Cambridge, UK, Cambridge University Press, 2014, pp 270–290.)

indings, in particular vacuolation, gliosis, and prion deposition.53,84 Because typical vacuoles in sCJD are illed with luid, it makes sense they would restrict water movement. In sCJD, MRI hyperintensities usually present with a typical neuroanatomic pattern of involvement.91,132 Three main patterns of GM involvement are recognized on DWI and/or FLAIR images91,143: concomitant cortical and subcortical involvement (≈two thirds of patients); only cortical involvement ( 20 mm in any diameter; no more than connecting bridges between individual lesions); Fazekas 3: conluent lesion (single lesions or conluent areas of hyperintensity ≥ 20 mm in any diameter). (From Prins ND, Scheltens P: White matter hyperintensities, cognitive impairment and dementia: An update. Nat Rev Neurol 11:157–165, 2015.)

detectable up to 10 years prior to onset of the motor clinical manifestation and worsens as the disease progresses122 (Fig. 15-9). Degenerative changes can also affect the frontal and temporal cortices.122 In addition, GM reductions can be seen in the hypothalamus and opercular cortex.115 A number of investigators have reported that in addition to atrophic changes, patients with HD present with areas of abnormal T2 signal hyperintensity in the basal ganglia.115

PARKINSON’S DISEASE Idiopathic PD is by far the most common cause of parkinsonism and should always be the diagnosis if a deinite secondary cause cannot be identiied. Deinitive diagnosis of idiopathic PD requires histologic demonstration of intraneuronal Lewy body inclusions in the

substantia nigra (SN) pars compacta.54 In most cases the diagnosis of probable PD can be made on clinical grounds, and no ancillary investigations are needed. However, in early PD the full triad of clinical symptoms and signs (bradykinesia, tremor at rest and rigidity) may not yet be manifested.88 CT scans can show nonspeciic atrophy with enlarged ventricles and sulci. Conventional MRI at 1.5 T with visual assessment of T2- and T1-weighted imaging does not reveal disease-speciic abnormalities in PD and, particularly in the early phases, the MRI appears normal.120 Its main clinical role is to exclude subcortical vascular pathology, rare secondary causes of parkinsonism (e.g., Wilson’s disease, NPH, or tumors, granulomas, or calciication of basal ganglia), and in discriminating atypical parkinsonian syndromes. With disease progression, indings remain nonspeciic, although a signal decrease in the SN on

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B FIG 15-9 MRI scans of control individuals, mutation carriers, and patients with Huntington’s disease (HD). A, Coronal images from controls and mutation carriers during the transition from premanifest stage to symptomatic disease over 10 years. Over this period, progressive atrophy of the striatum, whole brain, and white matter is evident and accompanied by increased lateral ventricle sizes. B, Voxel-based morphometric images from the TRACK-HD study showing regions for which the gray matter and white matter atrophy rates over 12 months were signiicantly different from individuals in the control group. (From Weir DW, et al: Development of biomarkers for Huntington’s disease. Lancet Neurol 10:573–590, 2011.)

proton density and T2-weighted images, as well as mild frontal and hippocampal atrophy, has been described.144 Nuclear medicine techniques including PET and SPECT allow conirmation of the clinical suspicion of PD by demonstrating presynaptic loss of the dopamine transporter. In PD, tracers of presynaptic dopaminergic function show a characteristic pattern of asymmetric reduction of striatal uptake, more pronounced contralateral to the clinically more affected side of the body33 (see Fig. 15-5). Typically the nigrostriatal dopaminergic projections to the posterior (dorsal-caudal) putamen are affected earlier and more severely than those to the caudate nucleus. The caudal-rostral gradient is attributed to (1) predominant degeneration of the ventrolateral portion of the SN that projects to the putamen and (2) relative preservation of the dorsomedial SN that projects to the caudate nucleus.60 Reductions in striatal tracer uptake correlate with pathologic measures (i.e., cell loss) and degree of motor disability, particularly bradykinesia and to a lesser extent rigidity; progression of the disease can be monitored using these tracers in longitudinal studies.16 In PD, FDG PET reveals a characteristic proile characterized by increased metabolism in the putamen/globus pallidus, thalamus, cerebellum, pons, and sensorimotor cortex and reduced metabolism in the lateral frontal, paracentral, and parietooccipital areas.41 The PD-related covariance pattern linearly correlates with clinical motor ratings (mainly with bradykinesia and rigidity rather than tremor) and increases with disease progression.

Atypical Parkinsonisms Atypical parkinsonisms can be caused by different neurodegenerative syndromes, such as the parkinsonian variant of multiple system atrophy (MSA-P), PSP, and CBS, which are frequently accompanied by denervation of both pre- and postsynaptic dopaminergic pathways and are usually levodopa resistant. MSA is a progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, parkinsonism, cerebellar ataxia, and pyramidal signs.55 MSA can be classiied into two subgroups: a cerebellar (MSA-C) and a parkinsonian (MSA-P) variant.55 The histologic hallmarks of MSA are α-synuclein-positive glial cytoplasmic inclusions in the oligodendroglia, which are required for the diagnosis of deinite MSA.55 PSP and CB degeneration are pathologically distinct causes of progressive atypical parkinsonism, characterized by hyperphosphorylated tau aggregates in the brain accompanied by neuronal loss and gliosis in a characteristic distribution.35 The large majority of PSP patients presents with Richardson’s syndrome, also known as PSP syndrome,81 characterized by postural instability leading to backward falls within the irst year of symptom onset, axial rigidity, progressive vertical ophthalmoplegia, dementia, and personality changes. CBD pathology can cause multiple different neurologic syndromes, including CBS, PSP syndrome, bvFTD, or PPA. CBS includes a mixed movement disorder (e.g., levodopa-unresponsive rigidity associated with apraxia, dystonia, myoclonus, and alien limb) and impaired cognition.6 In the early stage of the diseases, differential

CHAPTER 15 diagnosis among different atypical parkinsonian syndromes, and each of them with PD, is challenging because of similarity of symptoms and lack of preclinical markers of the disease. MRI can aid in the classiication of these patients, and several neuroimaging signs have been described for differentiating atypical parkinsonism syndromes from PD. A number of conventional MRI indings has been described as suggestive of MSA-P. These include a posterolateral putaminal decreased signal intensity on T2-weighted images, mainly due to iron deposition, covered by a rim of increased signal, mainly due to gliosis (Fig. 15-10). If pontocerebellar degeneration is present, lateral and longitudinal pontine ibers become evident as high signal manifesting as the “hot cross bun” sign (i.e., a cruciform linear area of high signal on T2-weighted images in the pons, with tiny round darker areas within the checkerboard of the cross; see Fig. 15-10). Cerebellar and pontine atrophy can be visually detected, along with hyperintensity of

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the MCP (see Fig. 15-10). Although putaminal atrophy appears to discriminate MSA-P from PD, T2 putaminal hyperintensity and a putaminal hyperintense rim may also occur in the latter condition.120 Speciicity of those abnormalities in differentiating MSA-P from PD and healthy controls is considered to be relatively high; in contrast, sensitivity seems to be insuficient, especially in the early stages of disease.120 PSP is characterized by a signiicant dorsal midbrain atrophy, especially of the anteroposterior diameter. Indirect signs of midbrain atrophy are the “penguin silhouette” or “hummingbird” signs on sagittal views120 (Fig. 15-11), where the shapes of the midbrain tegmentum (i.e., the bird’s head) and pons (i.e., the bird’s body) resemble a lateral view of a standing king penguin or hummingbird, and an abnormal superior midbrain proile (lat or concave vs. convex aspect in healthy subjects) is present. Other MRI indings in PSP patients are enlargement of the third ventricle, signal increase on T2-weighted images of

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FIG 15-10 Axial T2* gradient echo (A) and T2-weighted turbo-spin echo (B) MRIs show symmetric, abnormally low signal intensity of the putamen in two different patients with multiple system atrophy–parkinsonian type (MSA-P), which is surrounded by a regular hyperintense rim in B. C, “Hot cross bun” sign. D, Axial T2-weighted turbo-spin echo shows subtle diffuse hyperintensity of the white matter of the pons, middle cerebellar peduncles, and cerebellar white matter, with sparing of the corticospinal tracts in the basis pontis, which creates the “hot cross bun” sign (box). Note the marked thinning of the basis pontis and middle cerebellar peduncles. E, Sagittal T1-weighted gradient echo demonstrates diffuse atrophy of the brainstem (more pronounced in the basis pontis) and thinning of the folia of the cerebellar vermis. (From Mascalchi M, et al: Movement disorders: Role of imaging in diagnosis. J Magn Reson Imaging 35:239–256, 2012.)

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FIG 15-11 A, Hummingbird. B, Sagittal T1-weighted MRI from a patient with progressive supranuclear palsy shows the characteristic thinning of the anteroposterior diameter and the abnormal shape of the rostral midbrain tegmentum, exhibiting a concave upper proile and the posterior and central portions of loor of the third ventricle resembling the hummingbird’s long, thin, sharp beak. C, Axial T2-weighted image shows thinning of the midbrain and hypointensity of the substantia nigra. (From Mascalchi M, et al: Movement disorders: Role of imaging in diagnosis. J Magn Reson Imaging 35:239–256, 2012.)

the midbrain and inferior olives, atrophy and increased signal of the superior cerebellar peduncles on T2-weighted and FLAIR images, hypointense putamen on T2-weighted images (due to increased iron content), and frontal and parietal lobe atrophy. Only a few conventional MRI studies have assessed CBS patients. Despite this, several suggestive indings have been described, including a characteristically asymmetric frontal and/or parietal atrophy (including the pre- and postcentral gyri and central sulcus), with less frequent involvement of the temporal lobe (sometimes even global and symmetric), and a subcortical gliosis in the atrophic cortical gyri seen as high intensity on T2-weighted images. Unfortunately, none of these MRI abnormalities is considered to be of clearly diagnostic or even pathognomonic relevance for CBS, mainly because of the pathologic heterogeneity of this syndrome. SPECT and PET tracers investigating presynaptic dopaminergic function cannot differentiate PD from atypical parkinsonisms, given a similar nigrostriatal involvement in these conditions, although asymmetry of binding loss tends to be more pronounced in PD. FDG PET studies can contribute in the diagnostic workup between atypical parkinsonisms and PD. In contrast to PD, atypical parkinsonian syndromes show reduced lentiform nucleus glucose metabolism, which continues to decline as disease progresses.40 In addition, FDG PET shows bilateral hypometabolism of the putamen, brainstem, and cerebellum in MSA-P and hypometabolism of the brainstem, thalamus, and frontal cortex in PSP.40 The FDG PET pattern of CBS is characterized by a unilateral hypometabolism contralateral to the clinically affected side, with a predominance in the parietotemporal, prefrontal, cingular, and motor cortices as well as in the caudate and thalamus.52,68

AMYOTROPHIC LATERAL SCLEROSIS Motor neuron diseases (MND) are progressive neurodegenerative conditions that lead to severe disability and death.74 There is considerable variability in presentation, clinical course, and prognosis. These conditions are divided into several different clinical subtypes.74 ALS is the

most common (90% of all MND cases) and is characterized by upper (UMN) and lower motor neuron involvement of the bulbar, upper, and lower limb territories. Although a detailed clinical assessment remains the basis of the evaluation of patients suspected of having ALS, current international diagnostic criteria17 and European guidelines46 recommend that “all patients suspected of having ALS, where a plausible alternative unifying neuroanatomical explanation exists, should undergo an MRI of either or both the brain and whole cord depending on the clinical presentation.” Indeed, routine brain and spinal cord MRI can be useful in excluding several ALS mimic syndromes, including cerebral lesions (e.g., multiple sclerosis and cerebrovascular disease), skull base lesions, cervical spondylotic myelopathy, other myelopathy (e.g., foramen magnum lesions, intrinsic and extrinsic tumors, syringomyelia), conus lesions, and thoracolumbar-sacral radiculopathy. Corticospinal tract (CST) hyperintensities on T2-weighted, proton density-weighted, and FLAIR images are frequently found in ALS patients.24,125 CST hyperintensities, which are best followed on coronal scans, have been reported mostly bilaterally and are most frequently seen in the caudal portion of the posterior limb of the internal capsule. They typically extend downward to the ventral portion of the brainstem and less consistently upward through the corona radiata. Such lesions may occur more often in younger patients with greater disability.70 However, the reported frequency of conventional MRI abnormalities in ALS patients is very heterogeneous, ranging from 15% to 76%. More importantly, increased CST signal intensity has also been described in healthy individuals and, strikingly, in patients with other conditions such as Krabbe disease, X-linked Charcot-Marie-Tooth neuropathies, adrenomyeloneuropathy, and after hepatic transplantation.46 In ALS patients, the precentral cortex can present a low signal intensity (hypointense rim) on T2-weighted images.27,125 This so-called ribbon-like hypointensity is sharply contrasted by the hyperintense signal of CSF in the adjacent sulci. Over the past 15 years there have been signiicant advances in the identiication of advanced neuroimaging patterns in MND.28 International consensus was reached about essential and desirable protocols

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B

FIG 15-12 Sagittal (A) and axial (B) T1-weighted images show atrophy of the medulla and cervical spinal cord (arrow) with normal bulk of the pons and cerebellar vermis in a 13-year-old girl with Friedreich’s ataxia. (From Mascalchi M: Spinocerebellar ataxias. Neurol Sci 29[Suppl 3]:311–313, 2008.)

for MRI for studies in ALS,126 which are of the utmost importance in multicenter and longitudinal settings. In the absence of deinitive biomarkers of UMN involvement, a signiicant cortical thinning of the precentral gyrus, damage to the CST and corpus callosum assessed using DT MRI, and altered N-acetylaspartate levels in the primary motor cortex and CST should be considered suggestive of MND and hold promise for detecting UMN involvement before clinical symptoms become apparent.2

FRIEDREICH’S ATAXIA Friedreich’s ataxia is the most common inherited ataxia affecting children and young adults. It is commonly due to an expanded GAA trinucleotide repeat in both the alleles of a gene encoding the mitochondrial protein frataxin.78 Pathologic hallmarks of Friedreich’s ataxia are neuronal loss and shrinkage of the spinal ganglion cells and Clarke’s column of the spinal cord, with degeneration of peripheral nerves and spinocerebellar gracilis and cuneatus tracts.78 The cerebellar cortex is spared, whereas there is cell loss in the dentate nuclei and gliosis of the cerebellar WM.78 Cerebral cortical GM abnormalities are usually limited to the primary motor cortex, although damage to the visual cortex can occur. Hypertrophic cardiomyopathy can be the cause of death in advanced phases. MRI reveals a pattern of spinal atrophy85,86 in which the neurons of the sensory ganglion of the spinal nerves and the Clarke’s columns in the spinal GM are predominantly affected (Fig. 15-12). MRI shows atrophy of the spinal cord extending to the medulla, with a slight widening of the fourth ventricle. Symmetric signal changes in the posterior and lateral columns of the cervical spinal cord are found. Atrophy of the cerebellar or cerebral cortical GM is not remarkable in Friedreich’s ataxia, whereas volume loss of the deep cerebellar WM, which correlates with severity of the clinical deicits, was reported.34 Atrophy of the posterior cingulate gyrus, paracentral lobule, and middle frontal gyrus was also found.49 Acknowledgment: We would like to thank Drs. A.I. Holodny, A.E. George, M.J. de Leon, S. Karimi, and J. Golomb for the earlier version of the chapter.

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127. van de Pol LA, Hensel A, van der Flier WM, et al: Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 77:439–442, 2006. 128. van Dijk EJ, Prins ND, Vermeer SE, et al: Frequency of white matter lesions and silent lacunar infarcts. J Neural Transm Suppl 25-39:2002. 129. van Straaten EC, Scheltens P, Knol DL, et al: Operational deinitions for the NINDS-AIREN criteria for vascular dementia: An interobserver study. Stroke 34:1907–1912, 2003. 130. Virhammar J, Laurell K, Cesarini KG, et al: Preoperative prognostic value of MRI indings in 108 patients with idiopathic normal pressure hydrocephalus. AJNR Am J Neuroradiol 35:2311–2318, 2014. 131. Viswanathan A, Greenberg SM: Cerebral amyloid angiopathy in the elderly. Ann Neurol 70:871–880, 2011. 132. Vitali P, Maccagnano E, Caverzasi E, et al: Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 76:1711–1719, 2011. 133. Vonsattel JP, Myers RH, Stevens TJ, et al: Neuropathological classiication of Huntington’s disease. J Neuropathol Exp Neurol 44:559–577, 1985. 134. Wahlund LO, Barkhof F, Fazekas F, et al: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322, 2001. 135. Weir DW, Sturrock A, Leavitt BR: Development of biomarkers for Huntington’s disease. Lancet Neurol 10:573–590, 2011. 136. Whitwell JL, Przybelski SA, Weigand SD, et al: Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: A cluster analysis study. Brain 132:2932–2946, 2009. 137. Whitwell JL, Przybelski SA, Weigand SD, et al: 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer’s disease. Brain 130:1777–1786, 2007a. 138. Whitwell JL, Weigand SD, Boeve BF, et al: Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 135:794–806, 2012. 139. Whitwell JL, Weigand SD, Shiung MM, et al: Focal atrophy in dementia with Lewy bodies on MRI: A distinct pattern from Alzheimer’s disease. Brain 130:708–719, 2007b. 140. Wozniak JR, Lim KO: Advances in white matter imaging: A review of in vivo magnetic resonance methodologies and their applicability to the study of development and aging. Neurosci Biobehav Rev 30:762–774, 2006. 141. Yamada F, Fukuda S, Samejima H, et al: Signiicance of pathognomonic features of normal-pressure hydrocephalus on computerized tomography. Neuroradiology 16:212–213, 1978. 142. Yi SH, Park KC, Yoon SS, et al: Relationship between clinical course and diffusion-weighted MRI indings in sporadic Creutzfeldt-Jakob disease. Neurol Sci 29:251–255, 2008. 143. Young GS, Geschwind MD, Fischbein NJ, et al: Diffusion-weighted and luid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: High sensitivity and speciicity for diagnosis. AJNR Am J Neuroradiol 26:1551–1562, 2005. 144. Zarei M, Ibarretxe-Bilbao N, Compta Y, et al: Cortical thinning is associated with disease stages and dementia in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2013. 145. Zeidler M, Sellar RJ, Collie DA, et al: The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 355:1412–1418, 2000. 146. Zerr I, Kallenberg K, Summers DM, et al: Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 132:2659–2668, 2009.

16 Functional Magnetic Resonance Imaging Sachin K. Gujar, Haris I. Sair, and Jay J. Pillai

INTRODUCTION Magnetic resonance imaging (MRI) is very adept at displaying structural anatomy of the brain in great detail. However, the correlation between anatomy and function is not always clear or apparent, and this becomes particularly dificult in situations where the anatomy deviates from the expected owing to developmental anatomic variation or if there is structural distortion by disease. A few short years after the clinical use of MRI for imaging the human brain, Ogawa et al.37,38 described the imaging technique they called blood oxygenation level–dependent (BOLD) contrast for MRI. They demonstrated that the sensitivity to paramagnetic effects of deoxyhemoglobin could be increased with the use of gradient echo (GRE) techniques and that this BOLD contrast followed physiologic changes and could provide in vivo real-time maps of blood oxygenation. The initial studies described drug-induced changes,38 but this was soon followed by studies describing the BOLD response to physiologic visual and primary sensory activation by two groups almost simultaneously in 1992.4,28,33 This BOLD technique is the most commonly used method for functional MRI (fMRI).

HEMODYNAMIC RESPONSE FUNCTION BOLD fMRI measures or demonstrates the effects of neuronal activity via the changes in the hemodynamic correlate.1 Deoxyhemoglobin is paramagnetic, whereas oxyhemoglobin is diamagnetic. The presence of paramagnetic deoxyhemoglobin in a blood vessel results in local susceptibility differences that produce signal decreases (hypointensity) on GRE T2* images. Because oxyhemoglobin is diamagnetic and does not cause similar susceptibility changes, the changes in oxygenation of blood can be observed as signal changes on the T2* images.59 On the onset of neural activity, because oxygen consumption is expected to increase, it is also expected that local deoxyhemoglobin concentration would increase and result in decreased MRI signal. However, following a small transient decrease in BOLD signal at the onset of neural activity, it has been observed that there is a much more pronounced increase in signal, implying a net decrease in deoxyhemoglobin concentration. This has been thought to result from a much larger increase in cerebral blood low in response to the initial increased oxygen extraction, bringing in more oxygenated blood (oxyhemoglobin), with consequent reduction in deoxyhemoglobin levels in the local voxels. This variation of the BOLD fMRI signal as a function of time in response to neuronal activity is known as the hemodynamic response function (HRF).21 The relationship between the underlying neural activity and the resultant hemodynamic response is also known as neurovascular coupling.1 BOLD signal changes occur in tissue (extravascular BOLD effect) as well as within the vasculature (intravascular), with additional signal changes also occurring within the larger vessels.25

Although the physics behind the BOLD response is fairly well understood, there have been numerous theories proposed to explain the neural basis of the BOLD response.13 The favored explanation is a relatively direct correlation between fMRI signal and synaptic activity via a neurotransmitter-driven hyperemia response.1,2

CLINICAL fMRI Most fMRI studies performed for clinical use are task-based studies that require the patient to perform a motor, language, or visual task in the MRI scanner while (typically) GRE T2*-weighted echo planar images (EPI) are rapidly acquired. Another less clinically established but promising BOLD technique that will be discussed later in this chapter is resting state functional MRI (rs-fMRI).

Task-Based fMRI Most fMRI performed clinically is task based, with ultrafast images (e.g., single-shot T2* GRE echo planar technique) obtained during performance of deined motor or sensorimotor, language, or other cognitive or visual tasks. The magnitude of the BOLD signal changes is relatively small and can be more pronounced on high-ield-strength magnets (at our institution, we perform our fMRI studies on a 3-tesla [T] scanner). Use of a block design for the fMRI examination (described later) and multiple repetitions also improve signal-to-noise ratio and BOLD contrast. The rapid EPI technique allows imaging of the whole brain with a temporal resolution of approximately 2000 milliseconds and a spatial resolution of approximately 3 to 5 mm. A typical fMRI study paradigm would acquire generally between 90 and 120 whole brain volumes in 3 to 4 minutes. Disadvantages of the EPI technique include heightened susceptibility artifacts, especially at the skull base. Spin echo methods with acquisition of T2-weighted images can also be employed to minimize these artifacts; however, they provide lower BOLD effect and lower contrast between images acquired during rest and activity states.25 The stimulus or the activation paradigms are essentially of two types: block design paradigms or event-related paradigms. Block design paradigms consist of alternating blocks/epochs of a previously deined task alternating with equal-duration blocks/epochs of rest or a control task (Fig. 16-1). In most sensorimotor or language paradigms, each epoch duration in a block design is approximately 20 to 30 seconds. Event-related paradigms or single event paradigms are designed with short periods of activation alternating with longer periods of rest, with MR acquisition methods designed to measure hemodynamic changes over several seconds.25 Advantages of event-related design include the ability to present very brief stimuli at irregular intervals. Disadvantages of such design include greater task dificulty, particularly for neurologically impaired patients, and much lower statistical power for equivalent-duration paradigms. In clinical fMRI, block

489

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Task

Rest

Task

Rest

Task

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FIG 16-1 Typical block design used for task-based fMRI examinations is depicted in this diagram. Equivalentduration epochs of rest alternate with epochs of sustained repetitive activity (motor, language, or visual task performance). The upper half of the image displays the summation of individual stimulus-related hemodynamic responses as effectively sustained increase in BOLD signal during the activity blocks compared to the resting blocks.

design paradigms are generally used because they are generally easier to perform, are more eficient, and produce more statistically robust results.65

Motor Tasks. All the motor tasks we use are designed as a block design paradigm, with 30 seconds of rest alternating with 30 seconds of activity within each cycle, with the visual (or aural) instructions to “stop” or “go.” The most common sensorimotor tasks include a foot movement task (with continuous bilateral gentle plantar lexion and dorsilexion of the foot at the ankle at a steady pace, or alternatively toe lexion and extension), a inger movement task (which includes bilateral simultaneous sequential inger tapping), and a vertical tonguemovement task (with continuous gentle up-and-down movement of the tongue at a steady pace, with special care to avoid movement of the jaw) that elicits activation related to the face motor area. Alternatively, lip-puckering may be used for eliciting activation in the lower face sensorimotor cortex. A variety of other hand movement tasks (e.g., hand opening/closing, squeezing) can be used to activate the hand representation area of the primary motor cortex. If one thinks of the diagrammatic representations of the motor homunculus from physiology textbooks, the hand representation is always displayed to be overrepresented and takes up a large portion of the motor strip. Because the hand motor tasks are relatively simple to perform and show good activation of the motor cortex, hand motor paradigms should be performed if the primary motor cortex is to be localized. The bilateral inger-tapping task is successful in eliciting activation of the primary motor as well as the somatosensory cortex of the precentral and postcentral gyrus, respectively, in addition to the supplementary motor area (SMA) along the medial aspect of the cerebral hemisphere5 (see Fig. 16-3). We often employ a more complex three-phase hand opening/ closing task (right hand followed by left hand and then by a rest phase) using a dynamic visual display as the cue to obtain motor cortical activation maps in the precentral gyrus while minimizing sensory cortex activation (Fig. 16-2). The foot/ankle movement task results in robust activity within the precentral gyrus near the superior termination of the central sulcus and more prominently in the paracentral lobule, with activation of the supplementary motor area. Cerebellar activation is commonly observed during motor tasks in the hemisphere contralateral to the activated primary motor cortex.

Language Tasks. Functional MRI has been shown to be reliable for the prediction of hemispheric language dominance.17,50,51 Numerous paradigms are typically used to elicit the activation in eloquent cortex related to language function. Certain paradigms have been specially designed to elicit activation primarily in the speech-production areas (expressive paradigms) in the receptive language regions (receptive paradigms), whereas others activate both regions. Language-activation paradigms may be further divided into semantic, phonologic, or verbal luency paradigms. In general, for clinical language fMRI, only covert

(silently thought) rather than overt (physically spoken) language tasks are used to minimize head/mandibular motion. The expressive paradigms have been designed to elicit activation in the inferior frontal gyrus (IFG) corresponding to the region of Broca’s area, the dorsolateral prefrontal cortex (DLPFC) over the convexity of the frontal lobe, usually in the hemisphere dominant for language, and in the premotor or language supplementary motor area (pre-SMA) along the medial aspect of the frontal lobes (Fig. 16-3). The receptive paradigms have been designed to elicit activation in the receptive language areas predominantly in the temporal and parietal lobes, most prominently in Wernicke’s area, which technically involves Brodmann area 22 in the posterior-most aspect of the superior temporal gyrus (STG), although activation is typically seen along the posterior aspect of the superior temporal sulcus (STS), middle temporal gyrus (MTG), and temporal occipital junction, as well as in the inferior parietal lobule, including the angular and supramarginal gyrus (SMG) (Fig. 16-4). Expressive paradigms. Some of the expressive language tasks commonly used at our institution include covert word-generation tasks such as the silent word–generation task and the object-naming task. During the silent word–generation task, the patient is asked to covertly generate multiple words starting with the presented letter of the alphabet. In the object-naming task, the patient is asked to silently name a series of presented objects. The control task uses a nonsense drawing for visual ixation in order to minimize the effects of visual cortex activation. Silent word generation has been compared favorably with the Wada test in the lateralization of language function.62,63 With this task, activation is typically identiied within the DLPFC and IFG, and variably within the cingulate language regions, as well as in the pre-SMA regions. This task produces robust activation and effectively lateralizes speech functions. A similar task is a verb-generation task where instead of a letter of the alphabet, clues are visually or aurally presented. The patient is then asked to generate related verbs. Object naming is a simple covert word-generation task intended to activate language cortical functions of the dominant hemisphere, including in the IFG in addition to other areas. An example of a phonologic task is the rhyming task. The more complex rhyming task alternates epochs of a series of word pairs with a series of images showing two rows of stick igures, where the subjects respond electronically if the word pairs rhyme or if the rows of stick igures match. Typical activation includes DLPFC, IFG, STG, and STS. Receptive paradigms. Examples of commonly used receptive (i.e., comprehension or semantic) paradigms include the sentence listening comprehension and sentence reading comprehension tasks, as well as the passive story-listening task. The sentence listening comprehension task alternates blocks of real sentences with garbled speech and requires the subject to respond via button presses on a keypad only if the content of the presented sentence is true. The reading comprehension task is a similar paradigm

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FIG 16-2 This 63-year-old right-handed woman with a right frontal lobe anaplastic astrocytoma (WHO grade III) underwent BOLD fMRI motor cortical mapping with three different tasks: right hand opening/closing is depicted in yellow, left hand opening/closing in red, and vertical tongue movement in light blue (cyan). Note that the tumor is expanding the right precentral gyrus and resulting in effacement of the right central sulcus. The tumor involves the portion of the precentral gyrus just inferior to the hand representation area and extends into the face representation area, which demonstrates asymmetrically decreased activation compared to the normal contralateral precentral gyrus. The asymmetric decrease in ipsilesional activation may be a relection of tumor-induced neurovascular uncoupling.

that uses written sentences instead of aural stimuli. These are useful for clinical questions regarding language localization in Broca’s area and Wernicke’s area. Another example of a simple receptive task is a passive listening task that alternates segments of a short story with garbled speech sounds. Activation is most typically seen within the STG and in the cortex lining the STS. Additionally, activation is seen within the STG and MTG, more anteriorly. Semantic paradigms. Semantic paradigms are more general purpose for language mapping than the expressive and receptive

paradigms described. These are designed to be useful for language lateralization as well as localization of key expressive and receptive speech areas in the dominant hemisphere. The sentence completion task requires the patient to covertly complete written sentences that have been displayed with the last word missing. The control block consists of simple designs or a nonsense series of scrambled letters arranged in the form of a sentence. For this task, the dominant IFG activation is seen, consistent with the dominant expressive speech area, together with left MTG activation, consistent with the dominant receptive speech area.

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FIG 16-3 This 35-year-old right-handed (with moderate ambidexterity) woman with a WHO grade III anaplastic oligodendroglioma involving the medial left frontal lobe underwent presurgical mapping with BOLD fMRI using both language and motor paradigms. The T2/FLAIR hyperintense mass is seen iniltrating and expanding the left superior frontal gyrus as well as a portion of the left middle frontal gyrus. This igure depicts the composite activation map from ive different tasks: sentence reading comprehension in magenta, silent word generation in red, sentence completion in yellow, and rhyming in light blue (cyan), as well as a bilateral simultaneous sequential inger-tapping task in green. The second row arrow displays the pre-supplementary motor area, and the top row arrow designates the slightly more posterior motor SMA. The large cluster of language-related activation just lateral to the mass in the middle row represents dorsolateral prefrontal cortex expressive language activation, whereas Broca’s activation is seen more inferiorly in the left inferior frontal gyrus in the bottom row. The hand representation area of the primary motor cortex is seen depicted in green just posterior to the posterior margin of the mass.

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FIG 16-4 This 37-year-old right-handed woman with a WHO grade II oligoastrocytoma involving the left parietal operculum underwent language mapping with three language tasks, as well as mapping of the face representation area of the primary motor cortex (PMC) with a vertical tongue-movement task (color-coded in magenta). The three language tasks include a passive story-listening task in dark blue, sentence-listening comprehension task in light blue (cyan), and a silent word–generation task in red. Note that the face representation area of the PMC is located just above the superior margin of the tumor, which involves the postcentral gyrus. The top arrow indicates Broca’s area involving the left inferior frontal gyrus, and the lower arrow indicates functional Wernicke’s area along the left superior temporal sulcus. This patient was lefthemispheric dominant for both expressive and receptive components of language.

There are other semantic decision paradigms such as noun-verb association tasks and word category association tasks that are not described in detail here.

Visual Paradigms. Activation of the visual cortex involves a large portion of the occipital cortex and has been investigated since the early days of fMRI research. Visual stimulation results in robust activation in the visual cortex, and visual stimuli typically involve different varieties of lashing checkerboard patterns. Such stimuli have been effective for both retinotopic mapping and assessing foveal vision.

Memory Paradigms. Memory paradigms have not gained general acceptance for clinical fMRI, although much work has been performed at a research level using such paradigms.17 These can be dificult to perform and interpret, and susceptibility artifacts near the skull base can be a major limitation. Reliable memory lateralization with such

paradigms has been dificult to accomplish. These are beyond the scope of this chapter and are not discussed in detail here.

PERFORMING CLINICAL fMRI The Setup Because the magnitude of the BOLD signal is small, use of a high-ieldstrength magnet is essential; although 1.5 T is acceptable, the current standard is 3 T. At our institution, we perform fMRI studies on a 3-T scanner using a multichannel head coil. The stimulus paradigm is administered visually by displaying text or instructions via projectormirror system or specialized goggles, or with auditory stimulus using specialized head phones especially for language/semantic tasks.

Pre-Scan Interview and Training Reviewing recent prior imaging studies allows planning of the fMRI study and selection of paradigms tailored to the individual patient.

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Furthermore, pre-scan patient training is essential to familiarize patients with the tasks, assess their ability to adequately perform them, and alleviate anxiety.44

allows greater lexibility in discovering task-related and non–taskrelated signals without necessitating assumptions about their time courses.8,9

Monitoring

Role of Streamlined Postprocessing Tools

Performance of foot, inger, or hand motor tasks can usually be monitored visually. Performance of some of the language tasks is monitored via patient responses/button presses, but performance of other covert language tasks cannot be directly monitored and must be assumed on the basis of the performance during the pre-scan training. Real-time maps allow monitoring of task performance and also permit assessment of bulk head motion. These enable the neuroradiologist to make real-time informed decisions to repeat poor runs that are due to inadequate performance or excessive head motion that may have otherwise resulted in a nondiagnostic exam.

Research-level BOLD fMRI postprocessing software is very accurate but relatively cumbersome, requiring signiicant experience in image processing, as well as computer programming, for generation of custom-made scripts for postprocessing. The main drawbacks in the use of such software include lack of U.S. Food and Drug Administration (FDA) approval and inability to eficiently export postprocessed images to picture archiving and communication systems (PACS) servers and neuronavigation systems. However, there are commercially available FDA-approved software packages now available that are more user friendly, allow for better image overlays on highresolution anatomic images, and are compatible with both PACS servers and neuronavigation software.18,43 This has enabled import of functional images into the operating room, such that neurosurgeons can use the data in surgical planning. These packages also provide multiple options for statistical thresholding (e.g., cross-correlation, P value, T-statistic) and quality control analysis. At the same time, the research software allows for additional processing in situations where processing with the commercially available packages is inadequate.

Postprocessing and Quality Control After acquisition of data, several preprocessing steps are needed before the inal statistical analysis and creation of activation maps. As a part of postprocessing at our institution, we perform an extensive quality control analysis that includes assessment of patient head motion, functional-anatomic alignment, susceptibility artifacts, and data outlier volumes.

Analysis of fMRI Images A variety of methods are available for analysis of fMRI. The most widely used is a regression analysis using a general linear model (GLM).16 The GLM can be written as Y = XB + U, where Y represents the fMRI data, X represents the design of the experiment, B represents the estimation parameters, and U represents the error term. For each voxel, a B is estimated that minimizes the error between the observed (dependent) data and a reference, or predictor. In clinical fMRI, a hemodynamic response function (HRF) convolved with the boxcar function of the task serves as the reference in a block-design paradigm. For cases with multiple tasks, each may be designated separately in the design matrix X, and corresponding beta coeficients calculated.15 Following GLM itting, an F statistic is calculated to determine how well the model explains a particular voxel’s time course. A high F statistic or low p value indicates that there is a high correlation between the model and the modulation of the voxel time course. A T-statistic is then calculated by contrasting the signal in one condition to a second (usually “control” or “rest”) condition. A typical fMRI study at 3 T may have approximately 100,000 voxels. As a separate GLM analysis is performed for each voxel, this is also referred to as a massive univariate analysis. Given the large number of calculations performed, various methods have been employed to ensure that type I (false-positive) errors in activation are minimized.30 Ensuring speciicity using multiple correction methods such as familywise error (FEW), Bonferroni correction, false discovery rate (FDR), or cluster-based thresholding must be balanced with the need to avoid type II (false-negative) errors, which are more serious in clinical fMRI because surgical resection of areas labeled as no activation may result in signiicant morbidity. There are many assumptions that must be met for fMRI analysis using GLM. Although most of these assumptions are beyond the scope of this book, one warrants discussion: fMRI GLM analysis relies on a canonical HRF to function as the basis for the reference. The HRF, however, may be variable across brain regions, across different age ranges, and even vary with speciic stimulus conditions.26,36,41 Thus alternate methods have been investigated for model-free analysis of fMRI, including independent component analysis (ICA), which

Challenges and Limitations BOLD fMRI is very sensitive to susceptibility and motion artifacts. Susceptibility artifacts can be especially problematic in patients who have had signiicant hemorrhage in the vicinity of the areas of interest or in those who have had prior surgery, with susceptibility artifacts from calvarial metallic implants/ixation devices. There may be situations where patients are not able to perform the tasks owing to lack of understanding, disability, or inability to cooperate for the exam. BOLD fMRI is also affected by so-called venous artifacts because of intravascular BOLD effects. These changes in blood low and oxygenation may propagate downstream in the brain vasculature and appear in larger draining veins distant from the active cortical areas. The venous location of the activation can, however, be conirmed by comparison of functional activation maps with high-resolution (contrast-enhanced) structural images. Another problem associated with fMRI in the clinical setting is neurovascular uncoupling. As mentioned earlier, BOLD fMRI is an indirect measure of neuronal activity based upon the related hemodynamic changes. The absence of activation on BOLD fMRI does not imply the lack of neuronal activity. There are conditions under which the BOLD response may be disturbed, as with large vascular malformations or brain tumors with associated neovascularity, some low-grade tumors, or in situations with severe proximal arterial stenosis or strokes, which may give rise to false-negative activation.17,44,64,65 Maps of cerebrovascular reactivity obtained using hypercapnia stimuli56 can be tools that provide an overall whole-brain view of the BOLD response. At our institution, we routinely use a breath-hold (BH) technique44,64 for this purpose. This BH technique involves shortduration BHs alternating with longer periods of normal self-paced relaxed breathing (we use a 16-second BH block with a normal breathing block of 40 seconds), repeated multiple times. Monitoring of task performance is performed using a standard respiratory belt. Postprocessing, however, needs to be performed with speciic modeling to account for the differing durations of the BH and normal breathing blocks. The information obtained can be used to validate the ability of a perfusion bed to respond to a physiologic stimulus and the reliability of the fMRI mapping data.44

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CLINICAL APPLICATIONS OF fMRI Clinical use of MRI is a relatively recent phenomenon, with over 15 years of collective experience. The main clinical applications are in presurgical evaluation and mapping of patients with structural lesions (e.g., brain tumors) and in patients with epilepsy.42 Presurgical mapping has been used extensively in patients with brain tumors. Preoperative fMRI studies have been demonstrated to be helpful to surgeons for mapping of eloquent cortex and proximity to the target lesion, allowing informed decisions to be made regarding potential risks or safety of surgical resection and the surgical trajectory; fMRI may inluence the need for intraoperative cortical mapping.39 When fMRI is used for presurgical planning, the choice of paradigms depends mainly upon the location of the lesion.6 For example, if the tumor is located in the posterior frontal lobe, motor paradigms can be used to map the motor strip/precentral gyrus. Presurgical mapping has also been extensively used in epilepsy patients, primarily for hemispheric language lateralization. In epilepsy patients, a higher percentage of patients display atypical language lateralization than in normal individuals, and sometimes there may be discordance between expressive and receptive language lateralization. It has also been used for motor and visual cortical mapping in cases where malformations of cortical development or other resectable epileptogenic lesions are thought to be in close spatial proximity to eloquent cortical regions.

RESTING STATE fMRI Principles Resting state fMRI (rs-fMRI) has emerged as a complementary tool to task-based fMRI (tb-fMRI) for analysis of brain function.20 In tb-fMRI an “active” state corresponding to the task is followed by a “rest” state in which a control task is presented to nullify or diminish taskassociated signals of no interest (e.g., signals related to attention in a task not speciically interrogating attention mechanisms). In rs-fMRI there is no explicit modulatory task given, and spontaneous changes in brain activity are recorded. As in tb-fMRI, currently the majority of MR-based imaging of resting state brain function uses the BOLD technique described previously. The spontaneous changes in brain activity are not random, with spatially distinct brain areas demonstrating patterns of variable temporal synchrony. This temporal synchrony occurs generally in the frequency range of approximately 0.1 to 0.01 Hz. When linking highly synchronous brain regions together, a set of intrinsic networks of the brain emerge.14

Processing Processing of rs-fMRI partially mirrors that of tb-fMRI to include slice timing correction when appropriate, motion correction/realignment, detrending, and spatial smoothing if necessary. However, additional processing steps are necessary depending on the analysis method used to diminish false correlations related to physiologic noise and motion. In fact, motion can signiicantly alter functional connectivity measurements, enhancing short-range connectivity and diminishing longrange connectivity.45,46 In studies where motion characteristics may differ on a global scale between groups, caution must be taken to account for these motion-related effects.23 In addition to motionrelated artifacts, physiologic noise of cardiopulmonary origin can also contribute to rs-fMRI artifacts.34 Here, ideal nuisance reduction involves prospective recording of cardiac and pulmonary signals to be regressed from the fMRI volumes obtained. However, insofar as

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real-time recording is often impractical, solutions have been derived that allow retrospective removal of noise, typically involving regression of signal from white matter and cerebrospinal luid from the rs-fMRI volumes.3,35 Need for removal of average global signal is debated.10,61 High-pass or bandpass iltering is commonly performed in seed-based analysis to limit signal detection in frequency bands of interest. Highmotion volumes of rs-fMRI may be removed to improve overall quality of the remaining signal.

Analysis There are multiple methods to analyze rs-fMRI data; however, the most common can be divided into seed-based correlation analysis and blind source separation.24 In seed-based analysis, seed regions may be placed in certain brain areas based on a priori hypotheses of connectivity in the study group. At its most basic, two seed regions can be placed to determine the connectivity between those regions. A voxel-wise correlation analysis of the whole brain may also be performed using a time course derived from a single seed. Multiple seeds or regions of interest can also be used to determine pairwise correlations across each, and graph theoretical methods can then be employed to quantitatively describe network measures. Graph theory offers an ideal method of describing whole-brain correlations; the basis of graph theory is the description of multiple pairwise correlations.55 In graph terminology, a node or vertex refers to each unit that forms a graph (e.g., each seed or ROI). The edge represents the connection between the nodes/vertices (i.e., correlation). Graphs may be directed or undirected, the latter indicating that information regarding edge directionality is absent. They may be weighted, where edges may have varying values depending on the strength of correlations, or unweighted, where magnitude information of the edges is absent. The total number of edges associated with a particular node represents the degree of the node. For a speciic graph, an average of the degrees of each node can be calculated, and any node with a higher degree compared to this average is considered a hub. Various clustering methods can be used to group together nodes with high degrees of interconnected edges to form communities or modules. These modules often correspond to different groups of intrinsic brain networks described below. Independent component analysis (ICA) has been the most widely used method of blind source separation in rs-fMRI. Here, multivariate rs-fMRI signal is decomposed into a set of maximally independent signals. ICA assumes that the source signals are independent of each other, the signals are linearly mixed, and the distribution of signals is non-gaussian. Multiple algorithms for ICA exist. In rs-fMRI, spatial ICA has consistently demonstrated a set of intrinsic brain networks (IBNs) that demonstrate unique spatial distributions.12 Although there is no consensus yet as to the exact constituents or the exact number of these IBNs, there are a limited group of IBNs that have been reliably demonstrated in the literature11,60 (Fig. 16-5).

Intrinsic Brain Networks. The most widely studied IBN is the default mode network (DMN). Regions of the DMN include the precuneus, the posterior cingulate (speciically the retrosplenial cortex), the medial prefrontal cortex, and the inferior parietal lobules.19 Although the exact function of the DMN remains unknown to date, it is thought to be involved in self-referential tasks or internal tasks.47 The DMN may be subdivided into several subcomponents depending on the data processing and analysis method used. The attention network may be separated into the dorsal attention network (DAN) and the ventral attention network (VAN). The DAN includes bilateral parietal lobes at the banks of the intraparietal

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DMN

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FIG 16-5 Canonical intrinsic networks of the brain extracted from rs-fMRI using group independent component analysis (ICA). For each network, only the right hemisphere is shown in lateral, dorsal, and medial views. Some of the networks are split across different ICA components for this speciic dataset; each subnetwork is shown in the same row, separated by dashed lines. Yellow indicates regions with high correlations for each map. DMN, default mode network; ATT, attention network; ECN, executive control network; SMN, sensorimotor network; VIS, visual network; AUD, auditory network.

sulci, as well as the frontal eye ields. The VAN includes the rostral aspect of the inferior frontal gyri bilaterally and the inferior parietal lobules. The executive control network (ECN), also referred to as the frontoparietal network, is related to tasks of executive functioning, typically lateralized, and consists of dorsal medial prefrontal cortex and the ipsilateral superior parietal lobule. The salience network (SAL) includes bilateral insula and the anterior cingulate gyrus. This network is thought to mediate the assigning of salience, or relevance, of stimuli and may engage other appropriate higher-order cognitive networks to subsequently process the data.32 A language network (LAN) has been variably described, and when shown includes portions of the inferior frontal gyrus, posterior banks of the superior temporal sulcus, and the supramarginal gyrus.57,58 The primary networks include the sensorimotor network (SMN; also known as the somatomotor network), involving the primary sensory and motor regions of the pre- and postcentral gyri as well as the supplementary motor area; the visual network (VIS), which as expected

includes the occipital lobe subserving the primary visual cortex; and the auditory network (AUD), which includes bilateral primary auditory cortex (Heschl’s gyri) and adjacent superior temporal gyrus. Additional networks are less commonly described in the literature, such as the basal ganglia network or the cerebellar network.

Applications of rs-fMRI Although signiicant progress has been made in attempting to use rs-fMRI as a viable clinical tool, at the current time the clinical applications are limited. At the group level, network dysfunction has been well described across a plethora of disorders. The most widely studied network, the DMN, appears to be universally affected.7 DMN aberrations in Alzheimer’s disease is well documented.53 Connectivity of the DMN has also been demonstrated to be different in patients with mild cognitive impairment who progress to Alzheimer’s, compared to those who do not.40 Interestingly the spatial distribution of atrophy in different types of neurodegenerative disorders appears to correlate with the spatial distribution of IBNs.52

CHAPTER 16

Functional Magnetic Resonance Imaging

The greatest potential of rs-fMRI in clinical practice is in the setting of presurgical mapping, where tb-fMRI is routinely used.54,67 There are several advantages of rs-fMRI compared to tb-fMRI in this setting. Because there is no need to perform a speciic task in rs-fMRI (other than to try to keep as motionless as possible), this technique is helpful in situations where patients are not able to perform tb-fMRI owing to lack of understanding (e.g., related to cognitive deicits or language barriers) or physical disability (e.g., inability to move an extremity). In addition, rs-fMRI potentially can be obtained in less time than is necessary for a typical tb-fMRI and gives a wealth of information pertaining to multiple networks in the brain, as opposed to a narrow functional domain speciically related to the task in tb-fMRI. rs-fMRI is also easier to implement because no stimulus presentation hardware or software is needed. tb-fMRI does have an advantage at the current time in having multiple options for easy-to-use software packages for processing and analysis. These packages, however, will undoubtedly offer rs-fMRI–based network visualization in the future as processing and analysis methods become standardized.

Future of rs-fMRI Signiicant advances have been made in assessing functional connectivity of the brain since the discovery of synchronous BOLD signals in the brain. Many studies have assumed temporally stationary correlations across rs-fMRI acquisition; however, recently dynamic functional correlations have been investigated and offer insight into time-varying connectivity changes.22,29,66 Although network dysfunction has been demonstrated at the group level across many disorders, single subject– level diagnosis has been challenging. Characterizing normal versus abnormal dynamic connectivity may potentially improve subject-level applications.49 rs-fMRI also has shown some promise in prediction, including cognitive function and recovery from disease. This may be helpful in clinical settings where outcome following injury is uncertain, or it may be helpful in selection of patients who would maximally beneit from intervention.27,31,48

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34. Murphy K, Birn RM, Bandettini PA: Resting-state fMRI confounds and cleanup. Neuroimage 80:349–359, 2013. 35. Muschelli J, Nebel MB, Caffo BS, et al: Reduction of motion-related artifacts in resting state fMRI using aCompCor. Neuroimage 96:22–35, 2014. 36. Neumann J, Lohmann G, Zysset S, et al: Within-subject variability of BOLD response dynamics. Neuroimage 19(3):784–796, 2003. 37. Ogawa S: Finding the BOLD effect in brain images. Neuroimage 62(2):608–609, 2012. 38. Ogawa S, Lee TM, Kay AR, et al: Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 87(24):9868–9872, 1990. 39. Petrella JR, Shah LM, Harris KM, et al: Preoperative functional MR imaging localization of language and motor areas: Effect on therapeutic decision making in patients with potentially resectable brain tumors. Radiology 240(3):793–802, 2006. 40. Petrella JR, Sheldon FC, Prince SE, et al: Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology 76(6):511–517, 2011. 41. Pfeuffer J, McCullough JC, Van de Moortele PF, et al: Spatial dependence of the nonlinear BOLD response at short stimulus duration. Neuroimage 18(4):990–1000, 2003. 42. Pillai JJ: The evolution of clinical functional imaging during the past 2 decades and its current impact on neurosurgical planning. AJNR Am J Neuroradiol 31(2):219–225, 2010. 43. Pillai JJ: The signiicance of streamlined postprocessing approaches for clinical FMRI. AJNR Am J Neuroradiol 34(6):1194–1196, 2013. 44. Pillai JJ, Mikulis DJ: Cerebrovascular reactivity mapping: An evolving standard for clinical functional imaging. AJNR Am J Neuroradiol 2014. 45. Power JD, Barnes KA, Snyder AZ, et al: Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59(3):2142–2154, 2012. 46. Power JD, Schlaggar BL, Petersen SE: Recent progress and outstanding issues in motion correction in resting state fMRI. Neuroimage 105C:536– 551, 2015. 47. Raichle ME, Snyder AZ: A default mode of brain function: A brief history of an evolving idea. Neuroimage 37(4):1083–1090, discussion 1097–1099, 2007. 48. Ranasinghe KG, Hinkley LB, Beagle AJ, et al: Regional functional connectivity predicts distinct cognitive impairments in Alzheimer’s disease spectrum. Neuroimage Clin 5:385–395, 2014. 49. Rashid B, Damaraju E, Pearlson GD, et al: Dynamic connectivity states estimated from resting fMRI identify differences among schizophrenia, bipolar disorder, and healthy control subjects. Front Hum Neurosci 8:897, 2014. 50. Rutten GJ, Ramsey NF, van Rijen PC, et al: fMRI-determined language lateralization in patients with unilateral or mixed language dominance according to the Wada test. Neuroimage 17(1):447–460, 2002.

51. Sabbah P, Chassoux F, Leveque C, et al: Functional MR imaging in assessment of language dominance in epileptic patients. Neuroimage 18(2):460–467, 2003. 52. Seeley WW, Crawford RK, Zhou J, et al: Neurodegenerative diseases target large-scale human brain networks. Neuron 62(1):42–52, 2009. 53. Sheline YI, Raichle ME: Resting state functional connectivity in preclinical Alzheimer’s disease. Biol Psychiatry 74(5):340–347, 2013. 54. Shimony JS, Zhang D, Johnston JM, et al: Resting-state spontaneous luctuations in brain activity: A new paradigm for presurgical planning using fMRI. Acad Radiol 16(5):578–583, 2009. 55. Sporns O: Structure and function of complex brain networks. Dialogues Clin Neurosci 15(3):247–262, 2013. 56. Thomason ME, Foland LC, Glover GH: Calibration of BOLD fMRI using breath holding reduces group variance during a cognitive task. Hum Brain Mapp 28(1):59–68, 2007. 57. Tie Y, Rigolo L, Norton IH, et al: Deining language networks from resting-state fMRI for surgical planning—A feasibility study. Hum Brain Mapp 35(3):1018–1030, 2014. 58. Tomasi D, Volkow ND: Resting functional connectivity of language networks: Characterization and reproducibility. Mol Psychiatry 17(8):841–854, 2012. 59. Turner R, Le Bihan D, Moonen CT, et al: Echo-planar time course MRI of cat brain oxygenation changes. Magn Reson Med 22(1):159–166, 1991. 60. van den Heuvel MP, Mandl RC, Kahn RS, et al: Functionally linked resting-state networks relect the underlying structural connectivity architecture of the human brain. Hum Brain Mapp 30(10):3127–3141, 2009. 61. Yeh CJ, Tseng YS, Lin YR, et al: Resting-state functional magnetic resonance imaging: The impact of regression analysis. J Neuroimaging 25(1):117–123, 2015. 62. Yetkin FZ, Hammeke TA, Swanson SJ, et al: A comparison of functional MR activation patterns during silent and audible language tasks. AJNR Am J Neuroradiol 16(5):1087–1092, 1995. 63. Yetkin FZ, Swanson S, Fischer M, et al: Functional MR of frontal lobe activation: Comparison with Wada language results. AJNR Am J Neuroradiol 19(6):1095–1098, 1998. 64. Zaca D, Hua J, Pillai JJ: Cerebrovascular reactivity mapping for brain tumor presurgical planning. World J Clin Oncol 2(7):289–298, 2011. 65. Zaca D, Pillai JJ: BOLD fMRI for presurgical planning: Part 1. In Pillai JJ, editor: Functional brain tumor imaging, New York, 2014, Springer Science + Business Media. 66. Zalesky A, Fornito A, Cocchi L, et al: Time-resolved resting-state brain networks. Proc Natl Acad Sci U S A 111(28):10341–10346, 2014. 67. Zhang D, Johnston JM, Fox MD, et al: Preoperative sensorimotor mapping in brain tumor patients using spontaneous luctuations in neuronal activity imaged with functional magnetic resonance imaging: Initial experience. Neurosurgery 65(6 Suppl):226–236, 2009.

17 Brain Proton Magnetic Resonance Spectroscopy Lester Kwock, Mauricio Castillo, Jay J. Pillai, and Alena Horská

INTRODUCTION The irst reported in vivo localized proton (1H) magnetic resonance spectroscopy (H1-MRS) studies of the human brain were irst reported over 20 years ago.37,109,132 Since these early studies, in vivo H1-MRS brain studies have been shown to be a powerful technique to noninvasively investigate the biochemistry of the human brain and to assess in situ the neurochemical proile of brain tissue. Thus they can provide biomarkers of neurologic disorders even in cases where lesions are not seen in conventional anatomic MRIs.21,96 The noninvasive quality of H1-MRS and the spatially localized MR techniques that have been developed to examine in vivo the neurochemical proile of brain tissue makes them suitable not only for diagnostic purposes but also longitudinal follow-up studies. They have proven to be important tools at many institutions for the noninvasive clinical assessment of numerous neurologic disorders such as brain tumors, epilepsy, white matter disease processes, metabolic disorders, and brain trauma.40,188,243,259,347 However, even though proton MRS has been incorporated into clinical protocols and is accepted at many institutions worldwide,253 it is still considered an investigational technique by some healthcare organizations, who indicate that at the present time there has been “no large multicenter trial published demonstrating any added beneit of MRS over MRI in diagnosing or monitoring pathological processes such as brain tumors, and no clinical trials demonstrating improved outcomes evaluated with MRS alone compared to patients evaluated with conventional imaging modalities have been reported.”3 What is not understood by these healthcare organizations is that MRS and MRI are not competitive techniques but rather complementary techniques that can “add value” to the MR diagnostic procedure and lead to better patient management decisions. MRS provides information about the metabolic proiles of lesions, whereas conventional MRI provides anatomic proiles, and in most cases it should not be used alone in making clinical diagnostic decisions but used in conjunction with the clinical history of the patient and information from conventional anatomic and advanced MRI techniques. As an example, Moeller-Hartmann and coworkers237 examined the diagnostic beneits of adding MRS to a conventional anatomic MRI study of intracranial mass lesions (i.e., infarctions, primary brain tumors, metastatic lesions, primitive neuroectodermal tumors, abscesses). In this study they found that with conventional MRI alone, 96 out of 176 correct diagnoses were made (55.1%). Adding H1-MRS information to the MRI indings led to an increase in the number of correct diagnoses from 96 to 124 out of the 176 cases (a 15.4% increase in correct diagnoses). By adding MRS to the MRI study, the number of incorrect diagnoses decreased from 27 (15.3%) for MRI alone to 16 (9.1%). Similarly, in a 2012 study165 it was shown that H1-MRS added value to conventional MRI information in the preoperative characterization of the type and grade of brain

tumors. This study found that information obtained from “H1-MRS signiicantly improved the radiologists’ MRI based characterization of grade IV tumors (glioblastomas (GBs), metastases, medulloblastomas, and lymphomas) in the cohort” (area under the receiver operating curve [AUC] from 0.85 in the MRI [alone] to 0.93 in the MRI plus MRS reevaluation [MRI plus MRS] and also in the less malignant glial tumors [AUC in the MRI reevaluation was 0.93 versus 0.81 in the MRI alone]).165 This chapter will not review the basic principles of MRS and in vivo H1-MRS/MRSI of the human brain. The fundamental principles of this technique have been presented in detail elsewhere.187,271 The main body of this chapter will concentrate on the complementary use of H1-MRS with advanced MRI techniques (i.e., diffusion-weighted imaging [DWI], perfusion-weighted imaging [PWI], and permeability), and conventional MRI to improve the accuracy of diagnosis and delineation of brain tumors and in therapeutic decision making. The major reason for this is because of the important indings and recommendations on the use of MRS recently published by the MR Spectroscopy Consensus Group.253 This group was formed in 2011 under the auspices of the International Society of Magnetic Resonance in Medicine and is composed of leading imaging scientists, neuroradiologists, neurologists, oncologists, and clinical neuroscientists from universities, as well as vendors from the United States, Europe, and Asia. This international group was charged with the task of documenting “the impact of H-1 MR spectroscopy in the clinical evaluation of the central nervous system.” One of the major conclusions and recommendations of this group was that “MR spectroscopy adds diagnostic and prognostic beneits to MR imaging and aids in treatment planning and monitoring of brain cancers,” and that “clinical imaging centers specializing in combined use of MR imaging and spectroscopy should be established in all major clinical neurologic centers that offer standardized MR spectroscopy procedures for improved patient management.”253 This conclusion was based on the substantial body of both basic science and clinical MRS research that has been performed over the past 2 decades worldwide, with consistent results found across laboratories. This chapter will demonstrate that MRS, especially if combined with advanced MRI techniques, (1) can improve the diagnostic accuracy identifying neoplastic from nonneoplastic brain processes, (2) can identify the presence or absence of speciic metabolites in the 1H MR spectrum that can be used as biomarkers to identify various tumor processes, and (3) that the combination of conventional and advanced MRI and MRS can reduce the need for more invasive diagnostic procedures to assess the cellular characteristics of untreated and treated brain tumor processes. The MR paradigms described in the brain tumor studies can serve as models for the potential development of combined MRS and MRI techniques to increase diagnostic accuracy and modify patient

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treatment planning to improve the therapeutic outcomes in other central system disorders presented in this chapter and in the MR Spectroscopy Consensus Group report.253

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MRI VS. MRS There is no difference between the physical principals of MRI and MRS; both techniques are governed by the same principles of magnetism. MRI and MRS differ only in the manner in which the data obtained are analyzed and the type of information provided. In the case of MRI, data collected are analyzed in the time domain (namely, free induction decay signal; signal intensity vs. time) to obtain relaxation time (TR) information (namely, T1 [spin-lattice] and T2 [spinspin]) of the nuclei. The data from the time domain information is then used to generate an anatomic image. In MRS, the time domain information is converted to the frequency domain (signal intensity vs. frequency) via Fourier transformation of the free induction decay time domain signal. The frequency information generated via Fourier transformation of the time domain signal is used to form a distribution of the intensities of chemical groups associated with various metabolites versus their Larmor resonance frequencies (Fig. 17-1) to give a spectral proile of the metabolites within this region of the anatomic image. Thus the two MR techniques (i.e., conventional MRI vs. MRS) give different but complementary information about the region being examined. In the case of conventional MRI (namely, T1- and T2-weighted MRI), the information is mainly anatomic in nature, generated via water proton interactions with the tissues, whereas MRS gives information about the biochemical/metabolic proile of the anatomic region being examined. Advanced MRI techniques such as PWI312 and DWI255 give physiologic information about the vascularity and cellularity of the anatomic region being evaluated. This information is also complementary to the information obtained from conventional anatomic MRI studies and biochemical/metabolic MRS studies. The major advantage of employing MR techniques to assess a lesion is that these complementary diagnostic techniques are noninvasive and can be performed during the same examination session (normally < 1.5 hours) to obtain multiparametric diagnostic information.

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MRS Observable In Vivo Brain Metabolites Several important metabolites are evaluated in long echo time (TE) (135-288 milliseconds) proton MR spectra (Fig. 17-2): • N-acetylaspartate (NAA) • Choline (Cho) • Creatine/phosphocreatine (Cr/PCr) • Lactate (Lac) When short TEs (20-30 milliseconds) are used, a greater number of metabolites can be identiied in the MR spectra; in addition to NAA, Cho, Cr, and Lac, the following may be identiied34,51,92,149,240,274,290,296,354: • Glutamate (Glu) • Glutamine (Gln) • γ-Aminobutyric acid (GABA) • Myoinositol (MI) • Alanine (Ala) • Glucose (Gc) • Lipids and proteins • Scylloinositol/taurine Although it may appear advantageous to obtain spectra routinely at only short TEs to distinguish among different clinical entities, some

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FIG 17-2 Normal brain spectra. A, Long echo TE = 135 ms. B, Short echo TE = 30 ms.

CHAPTER 17

Brain Proton Magnetic Resonance Spectroscopy

disadvantages of short TE studies exist. For example, short TE spectra display greater baseline distortion, and estimating signal areas calls for more sophisticated processing software algorithms.248 However, to maximize metabolite information, both a short and long TE MRS study should be performed.92,132 N-Acetylaspartate. NAA accounts for the majority of the NAA resonance at 2.01 ppm; this signal is the most prominent one in normal adult brain proton MRS and is used as a reference for determination of chemical shift.24,180,181 The NAA signal also contains contributions from other N-acetyl groups, such as N-acetylaspartyl glutamate (NAAG), N-acetylated glycoproteins, and amino acid residues in peptides.24,180,181 NAA is second only to Glu as the most abundant free amino acid in the normal adult brain.211 The function of this amino acid is not fully understood despite its early discovery in 1956 by Tallan.330,331 From animal studies, NAA is believed to be involved in coenzyme A (CoA) interactions and in lipogenesis within the brain.16,31,44,86 Speciically, such studies suggest that NAA is synthesized in the mitochondria from aspartate and acetyl CoA and transported into the cytosol where it is converted by aspartoacylase into aspartate and acetate.31,57,86 Although NAA is widely regarded as a nonspeciic neuronal marker, it has also been detected in immature oligodendrocytes and astrocyte progenitor cells.296,346 Normal absolute concentrations of NAA in the adult brain are generally in the range of 8 to 9 mmol/kg, although regional and agerelated variations in NAA concentration have been noted by Kreis and others.178,229,274 In normal adults, NAA concentrations in cortical gray matter are higher than those in white matter; in infants the concentrations in gray and white matter are similar (highly active lipid synthesis in immature white matter accounts for this difference from the adult pattern).44,234 NAA concentrations are decreased in many brain disorders, resulting in neuronal and/or axonal loss, such as in neurodegenerative diseases, stroke, brain tumors, epilepsy, and multiple sclerosis, but are increased in Canavan’s disease.36

Creatine. The main Cr signal is present at 3.03 ppm and demonstrates major contributions from methyl protons of creatine and phosphocreatine as well as minor contributions from GABA, lysine, and glutathione.180,181 A second, usually smaller Cr signal is seen at 3.94 ppm. Cr is probably involved in maintenance of energy-dependent systems in brain cells by serving as a reserve for high-energy phosphates in neurons and as a buffer in cellular adenosine triphosphate/diphosphate (ATP-ADP) reservoirs.38,53,57,145,178,231 Thus the Cr signal is an indirect indicator of brain intracellular energy stores. The Cr signal is often used as an internal reference standard for characterizing other metabolite signal intensities because it tends to be relatively constant in each tissue type in normal brain; however, this is not always true in abnormal brain tissue, particularly in areas of necrosis.205 Cr concentrations in the brain are relatively high, with progressive increases noted from white matter to gray matter to cerebellum.274,296 Kreis and coworkers noted a mean absolute Cr concentration in normal adult brains of 7.49 ± 0.12 mmol/kg on the basis of a sample of 10 normal subjects,178 whereas Michaelis and colleagues reported a similar value of 5.3 mmol/kg.167,229 Total Cr values tend to be abnormally reduced in brain tumors, particularly malignant ones.52

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resulting in hypercellularity (e.g., primary brain neoplasms or gliosis) or myelin breakdown (demyelinating diseases) lead to locally increased Cho concentration, whereas hypomyelinating diseases result in decreased Cho levels.36,52 Kreis and coworkers have reported a mean absolute Cho concentration in normal adult brain tissue of 1.32 ± 0.07 mmol/kg.178 Michaelis and others have reported a similar value of 1.6 mmol/kg.167,229

Myoinositol. MI produces two signals noted at 3.56 ppm and 4.06 ppm. MI is the major component of the signal at 3.56 ppm, although contributions from MI-monophosphate and glycine are also present.290 MI is believed to be a glial marker because it is present primarily in glial cells and is absent in neurons.38 A role in osmotic regulation of the brain has been attributed to MI.296 In addition, MI may represent both a storage pool for membrane phosphoinositides involved in synaptic transmission and a precursor of glucuronic acid, which is involved in cellular detoxiication.51,53,151,177 A derivative, MI-1,4,5-triphosphate, may act as a second messenger of intracellular calcium-mobilizing hormones.53,60 The mean absolute concentration of MI in normal brain tissues obtained in the Kreis series was 6.56 ± 0.43 mmol/kg.178 MI concentrations are abnormally increased in patients with demyelinating diseases, Alzheimer’s disease, and low-grade brain tumors.53,54,229

Lactate. Lac resonance is identiied as a doublet (splitting into two distinct resonant signals separated by 7 Hz), produced by magnetic ield interactions among adjacent protons (referred to as J-coupling) centered at 1.32 ppm. A second Lac signal is present at 4.1 ppm but tends to be inconspicuous on spectra obtained with water suppression owing to its proximity to the water signal.53 Because Lac levels in normal brain tissue are absent or extremely low ( 60 years) reported decreased frontal NAA and increased parietal Cho and Cr with aging.131 Lac signal is seen in preterm and small-for-gestational-age infants.19,250 However, in appropriate-for-gestational-age term infants, it is abnormal to ind higher than trace amounts of Lac, particularly following the irst few hours of life, and such abnormal amounts of Lac signify brain injury.25 In preterm infants, the levels of Lac decrease progressively until the age of 40 postconceptional weeks.25,197,201,264 Signiicant regional heterogeneity in spectral patterns has been noted both in the developing brain and in mature brains.7,136,166,178,273,353,359 In the developing brain, proton MR spectra demonstrate that different parts of the brain mature at different rates and at different times and that the more metabolically mature areas demonstrate lower MI and higher NAA levels than the less mature regions of brain; speciically, the basal ganglia, perirolandic cortex, and visual cortex mature before areas such as the frontal white matter, prefrontal cortex, and temporal cortex.25,155,207,353 NAA/Cho ratios in the frontal region were reported to be lower than those in the parietal lobe at birth, with subsequent increase during the irst 6 months of life.7,154 Lower NAA and higher Cho levels were detected in the allocortex compared to the isocortex in healthy children and adults.8,71 Tedeschi and colleagues have noted signiicant regional variations in metabolite ratios in adults335; NAA/Cho and NAA/Cr ratios varied by more than a factor of 2 for different brain regions, with high levels of Cho and Cr and low levels of NAA found in the cerebellum.158,359 High Cho levels were also reported in insular cortex, thalamus, and centrum semiovale compared to parietal or occipital gray and white matter; high NAA levels were detected in the centrum semiovale.22 In the mesial temporal lobe, the anterior mesial temporal lobe was found to have higher Cho concentration than the middle and posterior mesial temporal lobe.8

Evaluation of Primary Brain Tumors (Gliomas) Many different types of brain tumors have been studied with MRS, and fairly consistent patterns of metabolic abnormalities have been described in both glial and nonglial tumors.18,278 Proton MRS allows reliable differentiation of tumor margins from adjacent brain edema, which is often not possible with gadolinium (Gd)-enhanced MRI,52 which may under- or overestimate tumor size in approximately 40% of cases.252 A multitude of applications of proton MRS exist in the ield of brain tumor diagnosis and management, and MRS is clearly playing an increasingly valuable clinical role that complements the roles of conventional structural MRI and other advanced MRI techniques such as PWI and diffusion tensor imaging (DTI).

Noninvasive Histologic Grading of Gliomas. Although it is possible to clearly distinguish glial neoplasms from normal brain tissue by MRS, controversy exists regarding the reliability of MRS in distinguishing among different histologic grades of astrocytomas and other brain tumors.53,183,247,311 For example, Shimizu and associates demonstrated that through semiquantitation of MRS signal intensities as a ratio to that of an external reference, it was possible to predict tumor malignancy15,311,310; higher-grade brain tumors were associated with higher Cho/reference values and lower NAA/reference values in their series.318 This, in conjunction with indings from Tamiya’s group regarding high correlation between Cho/NAA and Cho/Cr ratios and cellular proliferative activity,332 provides substantial evidence that proton MRS may be useful in the prediction of tumor grade.199

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In a series involving children, linear discriminant analysis and proton MRS demonstrated an 83% success rate in establishing the correct diagnosis of histologic grade of brain tumors.358 In a series of 27 patients with biopsy-conirmed brain tumors, Meyerand and colleagues showed that the combination of Lac/water and Cho/water ratios obtained from regions of contrast-enhancing brain tumor (with normalization of each metabolite signal area to the area of the unsuppressed water signal) permitted differentiation of low-grade astrocytomas from anaplastic astrocytomas and GBs.226 However, not all studies have conirmed the ability of proton MRS to differentiate between different tumor grades. For example, Burtscher and colleagues have described a series of 26 intracranial tumors in which MRS allowed differentiation of iniltrative processes from circumscribed lesions but did not allow differentiation of different types of lesions within each category.45 In a multicenter study involving 86 cases of glial tumors, Negendank and coauthors showed that each type and grade of tumor was a metabolically heterogeneous group with signiicant overlap in spectral NAA/Cr and Cho/Cr ratios with tumors in other categories; all tumors demonstrated abnormally decreased NAA/Cr and increased Cho/Cr ratios with respect to normal brain parenchyma.247 Some of the reasons for these indings in early studies (i.e., before the year 2000) regarding the inability of proton MRS to reliably differentiate various tumor grades have included inconsistencies in quality of spectroscopic data among different institutions, use of only long TE spectra, and use of only singlevoxel technique; many of these problematic issues have been addressed in more recent studies.249 Studies have suggested that advanced physiologic MRI methods in conjunction with MRS may be more accurate for determination of tumor grade than MRS or anatomic MRI alone. For example, Law and colleagues demonstrated that relative cerebral blood volume (rCBV) perfusion MRI combined with proton MRS metabolite ratios data improved both sensitivity and positive predictive value (PPV) for the determination of glioma grade over structural MRI alone.192 The combination of rCBV, Cho/Cr, and Cho/NAA resulted in sensitivity, speciicity, PPV, and negative predictive value of 93.3%, 60%, 87.5%, and 75%, respectively, compared to 72.5%, 65%, 86.1%, and 44.1%, respectively, with conventional MRI alone. The low speciicity was due in part to the fact that high Cho levels were found in some low-grade lesions. El-Sherbeny and coworkers100 recently showed that inclusion of MI/Cr ratios in the MRS analysis in conjunction with the MRI information obtained from conventional and advanced MRI techniques added additional diagnostic value to the differentiation of the grade of the brain tumor. A number of studies have shown that MI/Cr peak area ratios over 0.6 are highly characteristic of low-grade gliomas.29,54,148 With the addition of MI/Cr ratios to MRS data, the sensitivity and speciicity of the MRI/MRS paradigm employed to determine the grade of the lesion was 91% and 90.5%, respectively, compared to the study of Law et al.,192 which found a 93.3% sensitivity and only a 60% speciicity. The study of El-Sherbeny examined 93 patients with histologically conirmed brain tumors (31% low grade and 69% high grade). More recently, Caulo and colleagues18 reported a quantitative multiparametric MRI evaluation of 110 patients with either low- or highgrade gliomas (rCBV, apparent diffusion coeficient [ADC]), MRS (Cho/Cr and Cho/NAA), and conventional MRI that incorporated the analysis of four heterogeneous MRI tumor regions. They found that taking into account the heterogeneous nature of the gliomas and combining the studies with both advanced and conventional MR techniques signiicantly improved the discrimination between low- and

high-grade brain gliomas (sensitivity of 84.4%, speciicity of 100%, and an AUC of 0.95). A meta-analysis by Hollingworth and colleagues published in 2006 explored the overall clinical utility of MRS in the characterization of brain tumors and shed some important light on the potential role of MRS in the differentiation of various tumor types.140 It concluded that MRS was accurate in differentiating high- and low-grade tumors.140 Speciically, based on receiver operating characteristic (ROC) curve analysis of multiple studies examining sensitivity and speciicity of proton MRS for differentiating high- from low-grade tumors, the study found excellent values for this purpose in the AUC in multiple studies.140 In studies by Devos and Lukas and colleagues, AUC values of 94% and 96% in studies using long and short TE, respectively, were obtained.91,207 In Hollingworth’s meta-analysis, two studies also showed excellent ability of proton MRS to differentiate between high- and low-grade gliomas; speciically, Herminghaus and coworkers showed in their study of 90 patients that the sensitivity and speciicity of proton MRS for the differentiation of high-grade from low-grade tumors were 95% and 93%, respectively.135,140 In addition, Astrakas and associates demonstrated in their cohort of 66 patients that by using a combination of MRS parameters (namely Cho/Cr and Lac/Cr; threshold value = 1.8), an AUC value of 96% was obtained for the sensitivity and a speciicity of 88% for differentiation of high-grade from lowgrade tumors.9,141 Astrocytomas typically demonstrate reduced NAA levels, moderately reduced Cr levels, and elevated Cho levels compared to normal brain parenchyma (Fig. 17-3 and Table 17-1).43 These absolute reductions result in abnormally low NAA/Cr ratios and elevated Cho/Cr ratios (see Table 17-1).296 NAA levels in astrocytomas are reduced to 40% to 70% of the levels seen in normal brain parenchyma.220 Furthermore, Cho has been reported to be substantially elevated in more malignant astrocytomas, and this may be secondary to increased cellularity and cell membrane synthesis.220,350 There is evidence to suggest that the elevation of Cho is proportional to the degree of tumor malignancy.52 However, highly malignant primary brain tumors with extensive necrosis may actually demonstrate decreased levels of Cho. Elevated Cho levels are seen more consistently in anaplastic astrocytomas (which do not demonstrate histologic evidence of necrosis) than in glioblastoma multiforme (GBM), and ependymomas display higher Cho/Cr ratios than those noted for astrocytomas in general.52,358 Lac levels may be elevated in some astrocytomas as well. However, a higher incidence of Lac in more aggressive or higher-grade astrocytomas is controversial because Lac may also be present in benign pilocytic astrocytomas.156,247,252,344 It is thought that Lac may be present

Choline/Creatine and Myoinositol/Creatine Proton Metabolite Peak Area Ratios in Normal Brain and Gliomas TABLE 17-1

TE = 135 msec Normal (n = 20) Grade 1 (n = 5)* Grade 2 (n = 5)† Grade 3 (n = 5) Grade 4 (n = 10)

TE = 30 msec

(Cho/Cr)

(Cho/Cr)

(MI/Cr)

1.08 ± 0.19 2.25 ± 0.44 1.66 ± 0.28 2.72 ± 0.49 3.23 ± 1.06

0.91 ± 0.15 1.57 ± 0.26 1.28 ± 0.63 2.06 ± 0.36 2.15 ± 0.66

0.42 ± 0.16 1.95 ± 0.74 1.02 ± 0.13 0.49 ± 0.21 0.33 ± 0.17

*WHO grade 1 lesions were biopsy-conirmed pilocytic astrocytomas. † WHO grade 2 lesions were conirmed oligodendrogliomas.

Myoinositol Cho

Cho

1.5

Ins dd1

0.10 Cr

1.0

0.5

Cr

Ins dd2

Gtx m3

Gtx dd Cr2

NAA NAA NAA dd2 dd1 Gtx m1 Gtx m2

0.05 Cr2 NAA

0.0

0.00

4

3

2

1

4

ppm TE = 20

A

3

2 ppm TE = 135

Cho 0.4

0.3 Cr 0.2 Cr2 0.1 NAA 0.0 3

4

B

2

1

ppm

Cho

0.6 Cr NAA

0.4 Cr2

0.2

Ins dd1

0.0 4

C

3

2

1

ppm

FIG 17-3 A, Grade II astrocytoma. A representative single-volume proton MR spectrum of a histologically proven low-grade glioma using a STEAM sequence for the TE = 20 msec spectrum and a PRESS sequence for the TE = 135 msec spectrum. The TR used was 1500 msec in both the TE = 20 and TE = 135 msec studies. Note the intensity of the myoinositol (3.56 ppm) and choline (3.2 ppm) resonances in the low-grade lesion compared to the higher-grade gliomas. B, Glioblastoma multiforme (GBM). Representative singlevolume proton MR spectrum of a histologically proven GBM using a PRESS sequence at TE = 135 msec and TR = 1500 msec. C, TE = 30 msec proton spectrum of GBM. Note the lower myoinositol resonance compared with the grade II lesion and the elevated choline signal at both TE = 30 and 135 msec.

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across the entire spectrum of grades of astrocytomas because Lac may arise not only from hypoxia developing within the tumor itself as a result of disruption of normal vascular networks but also from necrosis or cysts within the tumor.52,53,311 Lac levels may be elevated in all cysts regardless of etiology.52 The presence of Lac has been attributed to (1) the extent of anaerobic glycolysis, (2) the eficiency of electron transport, and (3) the rate of washout from tumor tissue.156,202,296 In highly vascular tumors, Lac may be rapidly removed from the tumor as a result of increased blood low; therefore, even in high-grade vascular tumors, Lac may not be present in the MR spectra.52 The value of Lac identiication following radiation therapy or surgery is controversial, but the Lac concentration may be proportional to the original tumor size.52,338 Lac has been reported following radiation therapy and surgery, including stereotactic biopsy, although postsurgical porencephaly may lead to artifactual increases in Lac levels because cerebrospinal luid (CSF) is known to be rich in Lac.52,208 The presence of elevated lipid levels has also been used to differentiate low-grade from high-grade neoplasms.202,246,251,272,344 Some studies suggest that mobile lipids tend to be present in higher-grade neoplasms, with highest levels noted in GB; however, although high levels of mobile lipids may be speciic for anaplastic astrocytoma or GB, their absence in MR spectra does not exclude the possibility of such high histologic grades.247 Lipids may originate from tumor cells within highgrade astrocytomas, macrophages along the tumor periphery, or areas of necrosis.52 Lipids may be present as a result of microscopic cellular necrosis, which may not be apparent on conventional MRIs.52 There are inherent limitations of histopathologic grading of gliomas that make it a somewhat imperfect gold standard for tumor assessment. For example, there is the intrinsic sampling error associated with current stereotactic biopsy, which is frequently based on enhancing components of tumor, when HGGs are known to iniltrate nonenhancing parenchyma following the vascular channels of white matter tracts.170,192 Furthermore, in adults the biological behavior of low-grade astrocytomas with identical histologic grades is heterogeneous, with more than half of low-grade tumors eventually recurring as or evolving into more aggressive tumors.241 Some investigators believe that differences in MRS ratios of various metabolites, like differences in glucose metabolism in positron emission tomography (PET), may be of prognostic signiicance even if they are not of diagnostic value in such cases of low-grade neoplasms.142,170,171,247,261 Physiologic MRI, such as proton MRS, not only allows whole lesion evaluation but also allows for evaluation of metabolic abnormalities beyond the tumor margins.192

Deining and Delineating Metabolically Different Tumor Regions A major potential role for proton MRSI is in treatment planning and monitoring of tumor response. Clinical oncologists face a challenge when attempting to implement a treatment protocol that not only will effectively treat the patient’s central nervous system (CNS) tumor to improve survivability but also maintains the patient’s neurologic functions and avoids major treatment-associated morbidities. The capability of MRI to obtain anatomic images in any orientation and to vary between T1- and T2-weighted contrasts has greatly aided in identifying regions containing tumor and in the planning and monitoring of surgical and radiotherapeutic treatments. Furthermore, the use of intravenous Gd-containing contrast agents along with perfusion and water diffusion MRI techniques allow more accurate differentiation of tumor from edematous regions. However, conirming the presence and extent of malignant disease with conventional MR techniques is still problematic. This is especially true for highly diffuse primary brain tumors. For instance, not all

505

visible MR Gd contrast enhancement may correspond to the presence of tumor. Other biological processes besides the presence of a tumor can cause breakdown of the blood-brain barrier, which leads to contrast enhancement. Tumefactive inlammatory processes and treatment-induced necrosis are known to cause breakdown in the blood-brain barrier, leading to an MR appearance suggestive of tumor process.107 In addition, absence of Gd contrast enhancement does not always indicate that tumor is not present. WHO grade 2 gliomas commonly do not exhibit Gd contrast enhancement,89 and furthermore the heterogeneity of HGGs suggests that some regions of the tumor may enhance while other regions of the same tumor do not.200,279 Therefore treatments based solely on Gd contrast–enhanced T1-weighted MRIs to delineate the extent of the tumor may not target the full extent of the tumor and/or the most active regions of the tumor.277 Similar ambiguities with T2-weighted and FLAIR MR tumor imaging have also been found.324 Accurate diagnosis and delineation of tumor extent is critical to the clinical management of patients with intracranial tumors. Both surgical and radiotherapy tumor treatment plans are based on the conventional MRI techniques described previously and have been shown to be inadequate by themselves to accurately diagnose and delineate tumor extent. Depending on the tumor type, these MR techniques can only diagnose intracranial lesions with a 30% to 90% success rate.370 Biopsy is still considered the gold standard for determining cancer type and degree of malignancy. Once the lesion is diagnosed as a malignant brain tumor, planning of the surgical and radiotherapy treatments is based solely on the anatomic abnormalities observed on the conventional MRI studies. These conventional MRI studies, as indicated earlier, do not always provide an accurate picture of the extent or location of the tumor.195,268,277 This is especially true in determining the zone(s) of tumor iniltration with low to moderate rates of proliferation, regions of nonmigrating actively proliferating tumor, and regions of quiescent pseudopalisading migrating hypoxic tumor cells adjacent to necrotic regions.39,72 Usually, large uniform surgical and radiotherapy margins between 1 and 4 cm are treated to account for these regions.195,324,370 These margins may underestimate the extent of tumor iniltration, treat areas devoid of tumor (which increases the risk for normal tissue toxicity events), and/or undertreat tumor cells that are not actively proliferating in the planned treatment volumes. To obtain the most beneit from the newer neurosurgical and radiotherapy treatment approaches, such as computer-guided stereotactic neurosurgical techniques and the use of intensity-modulated and conformal radiotherapy treatment techniques, it is important that regions identiied for special attention be deined accurately. Areas of active tumor proliferation need to be identiied from areas suspicious for tumor extension, which are less proliferative but more iniltrative from areas that contain quiescent pseudopalisading migratory tumor cells around regions of necrosis. Noninvasive techniques that can provide information to improve our ability to characterize the genetic and molecular differences in the tumor populations present in a lesion and delineate the spatial extent of each population need to be utilized. This information, especially in HGG patients, may improve our ability to treat these lesions more accurately with the techniques now available and aid in the development of more targeted therapies to obtain better patient outcomes. In 2001, Dowling et al.95 took an important step in establishing MRS as a potential technique to aid in the mapping of tumor regions. Using a three-dimensional (3D) MRS technique, they evaluated the 3D MR spectra obtained from 28 brain tumor patients and correlated the histologic indings from speciic sites to the corresponding MR spectral voxels. Their results showed the following:

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(1) If the level of NAA is normal, the tissue within that voxel is normal. Conversely, abnormal levels of NAA correlate with abnormal tissue regardless of the underlying histologic indings (Figs. 17-4 and 17-5). (2) When a lesion contains a Cho peak area intensity greater than the peak area intensity of NAA and larger than the normal peak area intensity of Cho, tumor was always present (see Figs. 17-5 and 17-6). (3) The peak area intensity of Cho correlated with percentage of tumor in the sampled voxel. (4) Undetectable to near-normal levels of NAA and Cho are seen in areas of gliosis and necrosis (Fig. 17-6). (5) Image areas with similar appearance and enhancement may show different spectral patterns and histologic characteristics (see Fig. 17-6). These observations suggest that 3D MRSI could be a potentially important method that can be used to deine more accurately tumor margins, identify areas with the highest proliferative fractions, and identify posttherapy sites of tumor recurrence. For example, Pirzkall et al.268 studied whether the metabolic information provided by MRSI-deined volumes could improve the accuracy of target volumes for radiotherapy treatment planning compared to target volumes deined by MRI. Using elevated Cho and decreased NAA as criteria, Pirzkall et al.268 compared the MRSI-deined volumes to that deined by the Gd-enhanced T1- and T2-weighted MRI studies. They found that the T2 studies estimated, as judged by the volume of the hyperintense T2 region, the region at risk of containing microscopic disease as being as much as 50% greater than by MRSI. On the other hand, the Gd-enhanced T1 MRI studies suggested a smaller tumor volume and a different location for highly active disease compared to the MRSI study (Fig. 17-7). They concluded that “the use of MRSI to deine target volumes for RT treatment planning would increase, and change the location of the volume receiving a boost dose as well as reduce the volume receiving a standard dose.” This study suggests that inclusion of MRSI data in the treatment planning process could

potentially improve tumor control while reducing normal tissue radiation complications. This was clearly shown to have occurred in an external beam radiation therapy study of 26 patients with grade 4 gliomas in a study conducted by Chan et al.61 Patients with MRSI abnormalities (i.e., elevated Cho/NAA levels) outside of the MRIdeined target volume had decreased median survival times relative to those with MRSI abnormalities inside the MRI-deined target volumes (10.4 vs. 15.7 months). Applying a multiparametric MR scheme using information from H1-MRSI, PWI, DWI, and conventional MRI, Di Constanzo et al.93 found that the combination of these techniques provided useful information that could be used to further deine and improve the delineation and extent of tumor processes. In particular, this multiparametric study characterized more fully some of the more extreme spatial heterogeneities of tumor and could identify patterns for just tumor and edema alone, tumor and edema patterns in perienhancing regions of interest (ROIs) with abnormal signals on conventional MRI, and a tumor iniltrated pattern in apparently normal-appearing perienhancing ROIs. More importantly, this study suggested that changes in the MR parameters NAA, Cho, ADC, and rCBV could accurately classify the different perienhancing ROI patterns and be used reliably for guiding stereotactic biopsies, surgical resections, and radiation treatments of these regions.

MRS Spectral Proile of Proliferative, Hypoxic/ Pseudopalisading, and Iniltrating Glioma Populations One of the major factors that contributes to the poor therapy outcome in HGG patients is the subjective grouping of all HGGs by only their histologic characteristics, without considering the differences in molecular and genetic characters of different tumor populations within the observed HGG—namely, the main proliferating and stationary tumor body, the iniltrative population of HGG (which has a lower proliferation rate), and the quiescent pseudopalisading migratory tumor population adjacent to necrotic regions of the lesion. The

42Y NAA

0.3 Cho 0.2

Cr

0.1 Cr2

0.0

4

3

2

1

FIG 17-4 Proton MRSI of uninvolved brain region adjacent to low-grade lesion. Note level of NAA in abnormal FLAIR tumor region vs. uninvolved tumor region shown in square.

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507

Cho

0.4

0.3 Cr

NAA

0.2

0.1

Cr2

0.0

3

4

A

2

1

Cho 0.3

0.2 Cr

0.1 NAA

Cr2

0.0

B

4

3

2

1

FIG 17-5 Iniltrative grade 4 glioma (A,B). Note level of Cho relative to Cr and NAA in enhancing and nonenhancing brain regions. Both spectra are indicative of tumor being present.

molecular and/or genetic characteristics of these populations can affect different proliferative and/or iniltrative signaling pathways that are not normally considered when designing treatment plans. For example, with radiotherapy treatment of HGG, concomitant temozolamide chemotherapy is delivered; the reason for this is the mechanism of action of this drug. Temozolamide is a DNA alkylating agent that induces nicks in DNA, and if not repaired, daughter cells can inhibit replication, leading to increased apoptosis and increased radiation sensitivity. Inhibition of cellular replication occurs in the G2-M phase of the cell cycle,267 the most radiosensitive phase of the reproductive cycle. Thus the major effect of temozolamide is on tumor cells

in the most radioresponsive portion of the cell cycle. However, the level of response to temozolamide has been shown to be dependent on the genetic character of the HGG.221 Deletion on chromosome 10 (PTEN) of the phosphatase and tensin homolog leads to increased sensitivity to temozolamide. PTEN is a lipid phosphatase that plays a basic role in attenuating the phosphatidylinositol 3-kinase (P13K)/ Akt-1 signaling pathway; hence loss of PTEN can affect major oncogenic events during glioma genesis. Loss of PTEN occurs in about 36% of patients diagnosed with grade 4 gliomas; thus only about a third of the patients diagnosed with HGG will beneit from temozolamide treatment.193

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PART II CT and MR Imaging of the Whole Body

Choline

3.5

A

3.0

2.5

2.0 ppm

1.5

1.0

3.5

B

3.0

2.5

2.0 ppm

1.5

FIG 17-6 SPGR (spoiled gradient recalled acquisition in steady state) image and proton MRS spectral loca-

Cho/tNAA

tion of a patient with an oligoastrocytoma. A, MRI location and the MRS spectrum for a biopsy that yielded 75% tumor. Note the elevated Cho resonance and absence of NAA in this voxel. B, MRI location and MRS spectrum for a biopsy that correlated with the pathologic inding of necrosis, astrogliosis, and white matter. Note the low levels of Cho, Cr, and NAA resonances in this voxel region. Although the MRI intensity is similar to the region in A, signiicant differences in both the spectra and pathologic indings were found in these regions. (From Dowling C, et al: Preoperative proton MR spectroscopic imaging of brain tumors: Correlation with histopathologic analysis of resection specimens. AJNR Am J Neuroradiol 22:604–612, 2001.)

2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 Glioma grade II

A

B

Glioma grade III

C

FIG 17-7 Transverse T2-weighted (6490/98) MRIs in (A) patient 6 (astrocytoma grade II) and (B) patient 7 (oligodendroglioma grade III) superimposed with color-coded segmented Cho/NAA ratio image. Voxels in predominantly red areas (enclosed by black line) were determined as voxels in the tumor center; all other voxel positions were determined as voxels in the tumor border (enclosed by white line). Green lines show volume of interest of the MRS examination. Violet and blue, minimum value; red, maximum value. C, Box plot shows a signiicant and deinite difference (P = .001) for quantiied Cho/tNAA ratio averaged over the tumor center between patients with glioma grades II (n = 9) and III (n = 17). The central box represents values from lower to upper quartile (25th-75th percentile), the middle line represents the median, and vertical bars extend from minimum to maximum value. Small black squares show individual data points. (From Stadlbauer A, et al: Preoperative grading of gliomas by using metabolite quantiication with high-spatialresolution proton MR spectroscopic imaging. Radiology 238:958–969, 2006.)

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However, what about the two other tumor populations present in the HGGs in patients who respond to temozolamide—namely, the pseudopalisading migratory cells adjacent to necrotic regions and diffusively iniltrating tumor cells? Both of these tumor cell types should be refractory to temozolamide, because neither proliferate rapidly.72 Around areas of necrosis in HGG, the tumor cells show psuedopalisading.72 Data suggest that the pseudopalisading zone is the result of tumor cells migrating away from the necrotic region, and that necrosis selects for tumor cells that are more aggressive and more resistant to apoptosis-inducing therapeutic regimens.284 Similarly, data indicate that glioma cells that migrate out of the main tumor body have a decreased proliferative capacity and decreased susceptibility to apoptosis.164 These two populations may be the tumor cells responsible for regrowth and recurrence of HGG. Thus more information should be obtained that characterizes molecular signaling pathways activated in these populations, which will allow for more effective therapies to be developed. In the case of the migratory HGG cells, evidence indicates that treatment with inhibitors of migration does not affect apoptosis of migration-restricted/stationary glioma cells but can sensitize migrating glioma cells to cytotoxic agents.164

Proliferative Glioma Population: Cho/NAA Ratio, ADC, and rCBV Parameters. At present, the major role of MRSI in the surgical treatment planning for HGG is in guiding the neurosurgeon to regions that show high metabolic activity on biopsy (regions with elevated Cho levels and low NAA levels relative to normal brain tissue).95,223 In a study conducted by Gupta and colleagues,130 18 glioma patients were preoperatively examined with H1-MRSI and DWI along with conventional MR studies. This study was conducted to correlate quantitative presurgical H1-MRSI and DWI results with quantitative histopathologic characteristics of resected tumor tissue. The primary hypotheses to be tested were: “(1) glioma choline correlates with cell density, (2) glioma apparent water diffusion coeficient (ADC) correlates inversely with cell density, and (3) glioma choline signal correlates with cell proliferative index” as measured by MIB-1 immunostaining. The tumor-to–contralateral normalized Cho signal ratio (nCho = Chotumor voxel/Chocontralateral normal volume) and the ADC from resected tumor regions were determined from the preoperative MRI studies. The results showed that cell density correlated linearly with nCho but inversely with ADC values. No correlation was found between nCho and cell proliferative capacity. However, in a similar study conducted by McKnight et al.,223 using a normalized Cho/NAA (CNI) and Cho/Cr (CCrI) index instead of nCho index, they found that the normalized Cho/NAA but not the Cho/Cr ratios correlated signiicantly with the proliferation index of the tumors as determined by MIB-1 immunostaining (P < 0.001) and cell density measurements (P < 0.001) of the biopsy-obtained voxel sample. This inding suggests that voxels containing elevated normalized Cho/NAA ratios have the highest probability of being a region that has “high cell density, high proliferative fraction, and/or high ratio of cell proliferation to cell death.”223 As discussed previously, for surgical, chemotherapeutic, and radiation therapy clinical patient treatment decisions it is important to be able to delineate and identify, as conidently as possible, the various heterogeneous regions of the tumor so that the correct treatment plans can be applied to these regions. Thus the more noninvasive parameters or changes in the values of the parameters one can use to identify the tumor ROIs, the more accurate and more reliable the tumor map will be, which can be used to devise the most effective treatment paradigm for the patient. In the case of proliferative tumor regions, addition of the rCBV maps obtained from PWI studies can be

509

used to further identify and delineate the major proliferating regions of the tumor. Advanced MRI techniques have been developed that allow noninvasive study of tumor vascularity. Dynamic susceptibilityweighted contrast-enhanced perfusion MRI, used widely in clinical practice, relies on the T2* signal intensity change that occurs when the contrast agent passes through the tissues. This change in signal intensity allows calculation of the rCBV, and this parameter has been correlated with tumor vascularity.13,326 Studies have shown that gliomas that have higher rCBV also have higher mitotic activity,13,298 as judged from the histopathologic determination of the number of mitotic cells found in tissue sections from stereotactic biopsies obtained from the perfusion MRI study. More recently, Price et al.276 has shown that the rCBV in HGGs linearly correlated with cellular proliferation, as judged by MIB-1 immunostaining and histopathologic analysis of resected tumor section analyzed from preoperative PWI; r = 0.66, P < 001). Thus, using the correct thresholds for the Cho/NAA ratios, ADC, and rCBV for proliferating tumor regions, and coregistering this information with the anatomic MRIs can be used to improve the delineation and more accurately assess tumor regions having high proliferative capacity.

Hypoxic/Pseudopalisading Tumor Population: MRS Metabolic Proile and the Role of PET Imaging. Two other cell populations within the tumor that can lead to recurrence and/or resistance to therapy also need to be evaluated: (1) the quiescent pseudopalisading migratory hypoxic tumor population adjacent to necrotic regions and (2) the active iniltrating but low mitotically active tumor population migrating from the main tumor body.39,72 If neither of these populations are either resected or targeted for further treatment, they will lead to repopulation/recurrence and spread into other areas of the brain. In the case of the hypoxic/pseudopalisading population, this population is normally quiescent and if not surgically resected will be more resistant to standard radiotherapy treatments normally applied following surgery; this will lead to repopulation and spread of the tumor. In addition to their intrinsic resistance to radiation damage, this hypoxic tumor population is often refractory to the cytotoxic actions of conventional chemotherapeutic agents.316 Thus it is important to try to identify the location of this population for the design of augmented surgical, radiotherapy, and chemotherapy treatment plans. MRSI and conventional MRI, in conjunction with positron emission tomography (PET) of [F-18] luoromisonidazole uptake (F18FMISO) may be of use to map out the regions containing the hypoxic/ pseudopalisading tumor cells. F18-FMISO is a luoronitroimadazole compound that was one of the irst PET agents used for the pretherapy detection of hypoxic tumor populations in patients with tumors outside the CNS.283 With the advent of PET-MR clinical scanners, PET studies can be readily registered into the MRI and MRSI studies to produce anatomic maps combined with functional maps showing the distribution of proliferating and quiescent tumor populations in hypoxic regions. F18-FMISO PET can be used to image tumor hypoxia, because tumor cells show increased F18-FMISO uptake, and once taken up, it is exclusively trapped in hypoxic tumor cells because of the reduced cellular oxygen environment of these cells. F18-FMISO is cleared in normoxic tumor cells.364 The presence of hypoxia appears to be a common feature of HGGs that accumulate F18-FMISO.39,339 The hypoxic regions found in HGG have been shown to be associated with the regions adjacent to areas of necrosis where the hypoxic pseudopalisading cells reside.39,371 Recently Bruehlmeier et al.41 found that uptake and retention of F18-FMISO was consistently found in the periphery of the lesion adjacent to necrotic regions of the HGG.

510

PART II CT and MR Imaging of the Whole Body LIP/LAC

0.25

0.20

0.15

0.10 Cho 0.05

NAA

Ins dd1 Cr

0.00 ppm

A

3

2

1

B

FIG 17-8 A and B, MRSI volume showing necrosis (Lip/Lac) and tumor spectrum (elevated Cho/Cr levels).

MRSI can add support to the F18-FMISO PET indings because it has been shown that regions showing low Cho and NAA levels relative to normal brain normally indicate necrosis, astrogliosis, or regions with macrophage iniltration.95,323 However, these regions that appear to be necrotic may also contain quiescent pseudopalisading migratory tumor cells adjacent to necrotic centers,39,72 especially if they show spectra (obtained at TE = 30 milliseconds) that have elevated Cho/ NAA and Cho/Cr ratios, presence of lipid/Lac resonances, but overall lower levels of metabolites relative to normal tissue (Fig. 17-8). This spectral proile in fact may represent the most aggressive tumor population within HGGs and the major population responsible for the resistance and repopulation of tumors.39,284 In a study conducted by Martin et al.217 to determine the eficacy of MRSI in guiding biopsy, they found that in 17 out of 21 patients who had histologically conirmed biopsy tumor samples, the Cho levels were elevated relative to normal levels. However, in four patients with low Cho levels similar to those observed in necrotic regions, histologic evaluation of the biopsy sampled showed tumor. The representative MRSI spectra of one of these patients (Fig. 17-9) shows relatively elevated Cho/Cr and Cho/NAA ratios and an elevated lipid/ Lac resonance, suggestive of a necrotic region with actively proliferating tumor cells.

Iniltrative Glioma Population: Cho/Cr and Cho/NAA Ratio Proiles, rCBV, and Fractional Anisotropy. When targeting tumor biopsies or deining tumor treatment volumes, the iniltrating tumor population must be taken into account. To determine the usefulness of MRSI in assessing the degree of tumor iniltration, Ganslandt et al.112 performed MRSI studies on 7 patients with untreated grade 2 and 3 gliomas. The MRSI data sets were fused with the 3D MRI data sets and integrated into a frameless stereotactic system for imageguided interactive neuronavigation surgery. Tissue samples were obtained from three regions based on the Cho/NAA ratios found in the MRSI study: (1) normal-appearing brain region, (2) zone between spectroscopically pathologic and suspicious for iniltrating tumor volumes, and (3) maximum spectroscopically pathologic tumor volumes. The implementation of the MRSI data set into the frameless

stereotactic system was successful in all cases, and stereotactic biopsies were obtained from the MRSI-deined regions. In this study, a relationship between the tumor cell density and Cho/NAA metabolic changes were found (60%-100% in the maximum pathologic areas to 5%-15% in the border zones suspicious for iniltrating tumor). Another important inding of this study was that the tumor areas deined by the metabolic maps, which were conirmed histopathologically, exceeded the T2-weighted abnormal signal change in all cases by 6% to 32%. However, in four patients, biopsies obtained with normal Cho/NAA ratios showed the presence of tumor iniltration. It was suggested that the false-negative inding in these patients was due to the low resolution of MRSI with respect to the glioma borders. Another explanation could be that the Cho/NAA ratio relects primarily the proliferative capacity of the tumor cells and not necessarily the migratory capacity. Thus in iniltrative tumor zones, Cho/NAA levels may be normal or only slightly elevated because tumor cells are not dividing and/or displacing or destroying normal neural cells.368 Highly iniltrative cells normally only proliferate at vascular branch points,72 therefore in iniltrative white matter tumor regions the Cho/ NAA ratios may not be elevated. However, the Cho/Cr ratios may be elevated.368 This is shown by Wright to represent an iniltrative spectral tumor pattern.368 The iniltrating tumor pattern of gliomas is closely associated with the expression of matrix metalloproteinase 2 (MMP-2).69 Invasion of glioma cells involves the attachment of invading cells to the extracellular matrix (ECM), disruption of the ECM components, and subsequent penetration of the invading cell into adjacent brain structures. This is accomplished in part by the secretion of MMPs by the invading glioma cell to break down the ECM barrier, which impedes the iniltrating tumor cells from extending.62 Zhang et al.373 found a signiicant correlation between the Cho/NAA and Cho/Cr ratios and MMP-2 expression; it appears that the higher the ratios, the more invasive/ iniltrative the tumor. This is in agreement with the image-guided MRSI brain tumor biopsy studies of Croteau et al.84 Histologic analyses of tissue samples obtained from the MRSI-guided biopsy sites found that using contralateral Cr and Cho levels for normalization or ipsilateral NAA appeared to correlate with the degree of tumor

CHAPTER 17

Brain Proton Magnetic Resonance Spectroscopy

511

SVS Lipid

Cho Cr

C

NAA

A TSI

D

B 3.0

2.0

1.0

Chemical shift (ppm)

0.0

E

FIG 17-9 This patient had prominent lipid resonance and otherwise reduced metabolic levels on both SVS and MRSI. Although a modest degree of Cho elevation is evident on both spectra, it is dificult to deinitively infer the presence of tumor. However, on biopsy this area was conirmed to be recurrent glioblastoma. (From Martin AJ, et al: Preliminary assessment of turbo spectroscopic imaging for targeting in brain biopsy. AJNR Am J Neuroradiol 22:959–968, 2001.)

iniltration. They found that the degree of tumor iniltration increased with increasing Cho/NAA ratio and Cho/Cr ratios (minimal level of tumor iniltration had Cho/NAA = 1.09 ± 0.12 and Cho/nCr = 1.62 ± 0.09; maximum level of iniltration had Cho/NAA = 2.01 ± 0.18 and Cho/nCr = 1.98 ± 0.18). Using the Cho/Cr and Cho/NAA threshold ratios deined in the Croteau study for minimal level of tumor iniltration may be useful in delineating the more metabolic and proliferative tumor populations (Fig. 17-10) from the less proliferative iniltrating tumor ones (Figs. 17-11 and 17-12). Figure 17-11 shows a tumor that appears to be iniltrating into areas beyond the Gd T1-weighted enhancing regions of tumor. The Cho/Cr peak area ratios in these areas are 1.5 or greater. The region outside the enhancing area also shows Cho/NAA peak area ratios of 1.0 or less. This suggests that in areas outside the Gd-enhancing or T2-weighted hyperintense areas, in which Cho/Cr ratios greater than 1.5 and Cho/NAA levels of less than 1.0 occur (see

Fig. 17-12), there may be regions containing a mixture of normal cells and iniltrating tumor cells with lower rates of proliferation. In the area of enhancement or extending just beyond this area, where the MRSI Cho/Cr ratios are greater than 1.5 and the Cho/NAA ratios are greater than 1.0, are areas of active tumor proliferation and iniltration (see Fig. 17-11). The spectral pattern observed for the iniltrative tumor process is consistent with the iniltrative tumor spectral pattern found by Wright et al.368 (Fig. 17-13). Cho/NAA ratios may be low ( 1.5 and Cho/NAA > 1.0.)

FIG 17-11 Iniltrative tumor pattern. Note the proliferative tumor population (with Cho/Cr ratios > 1.5 and Cho/NAA > 1.0) is located primarily in enhancing region of tumor, whereas the predominantly migratory population (with elevated Cho/Cr ratio > 1.5 and Cho/NAA < 1.0) is outside the enhancing region.

as deined by the Cho/Cr peak area ratio of 1.5 or greater for tumor threshold (namely, where the Cho/Cr is > 1.5, it is highly probable tumor is present in this voxel). This observed Cho/Cr and Cho/NAA ratio pattern may suggest that the tumor is expanding via a more proliferative rather than an iniltrative pathway; this may be due to the more cortical location of this lesion, which predominantly affects white matter.72 Di Constanza et al.93 used an MR multiparametric approach to assess the extent and malignancy of cerebral gliomas. Thirty-one patients (21 high grade and 10 low grade) with gliomas underwent conventional MRI, H1-MRSI, DWI, and PWI studies prior to surgery and histologic examination of resected tissue. ROIs with high Cho (>1.3; Chovolume on tumor side/Chocontralateral normal volume) and or abnormal

Cho/NAA greater than 1.0 (normalized to ratio found in contralateral volume) were considered tumor or iniltrated tumor on the basis of previous neuropathologic correlation studies. From this multiparametric study of high-grade lesions, three tumor regions could be delineated: (1) Gd-enhancing tumor region (margin and mass), (2) perienhancing abnormal region containing tumor and edema, and (3) normal-appearing perienhancing region containing iniltrated tumor and normal brain parenchyma. The high-grade lesions containing the bulk tumor mass and enhancing margins (1) showed very high mean Cho/NAA ratios greater than 4.0 and Cho/Cr greater than 2.0 (normalized relative to contralateral normal region), high mean ADC values (1.24 ± 0.31 × 10−3 mm2/sec in bulk tumor vs. 0.77 ± 0.05 × 10−3 mm2/sec in normal brain region), and mean elevated

CHAPTER 17

Brain Proton Magnetic Resonance Spectroscopy

NORMAL UNINVOLVED REGION SLICE 2

513

SUSPECTED INFILTRATIVE TUMOR SPECTRUM

I : Integral

I : Integral

NAA I : 0.393

NAA I : 0.175

0.03 Cho I : 0.166

0.010

Cho I : 0.245 Cr I : 0.230

0.02

0.005 Cr2 0.01

Cr I : 0.0512

I : 0.0232

Cr2 I : 0.0868

0.000 0.00 ppm 4

3

2

1

ppm 4

3

2

1

FIG 17-12 Spectral pattern of (left) normal and (right) iniltrative tumor process (non–Gd-enhancing region).

rCBV of 3.70 in tumor vs. 0.98 in normal tissue. In the perienhancing abnormal-appearing region containing tumor and edema (2), the normalized mean Cho/NAA was found to be 3.3 and Cho/Cr was 1.76, the mean tumor ADC value was 0.92 ± 0.17 × 10−3 mm2/sec, and mean tumor rCBV was 1.68 ± 0.41. In the normal-appearing perienhancing region (3), the normalized mean iniltrated tumor Cho/NAA ratio was 1.55 and Cho/Cr ratio was 1.28, the mean ADC of this region was 0.86 ± 0.08 × 10−3 mm2/sec, and the mean rCBV of this region was 1.28 ± 0.16. The primary change in the ratios of Cho/NAA in the normalappearing iniltrated tumor region of a high-grade lesion is due to a change in the Cho levels and not to changes in the level of NAA. The mean normalized NAA levels in iniltrated tumor regions were 0.94 ± 0.23 vs. 0.96 ± 0.14 for the levels found in the normal contralateral side. In the bulk tumor mass, the mean NAA level was 0.31 ± 0.11, and in the perienhancing abnormal region (2) the mean NAA level was 0.58 ± 0.22. Thus in both regions 1 and 2 (as per above), the increased changes observed in the metabolite ratios appear to be due to decreased levels of NAA and increased Cho. This suggests higher tumor proliferative capacities in these regions as measured by increased Cho levels and loss of NAA levels. NAA is a neuronal marker, so the loss of NAA suggests either loss of neuronal activity or destruction due to tumor proliferation and invasion into these regions. However, in region 3 the almost normal level of NAA suggests that changes observed are due primarily to iniltrating tumor cells that are not proliferating rapidly. This interpretation is consistent with the changes in rCBV observed in tumor regions (2-3) of this study. Price et al.276 showed that high-grade brain lesions that have increased mitotic activity also have higher rCBV values. These investigators showed that rCBV correlated signiicantly with MIB-1 labeling index and not with tumor cell packing, which suggested that increased tumor vascularity as measured by rCBV was more dependent on cellular proliferation than just the number of cells present. Low-grade lesions demonstrated the same trend with respect to Cho/NAA, Cho/Cr, ADC, and rCBV values in bulk tumor versus

iniltrated tumor regions. The bulk of the tumor showed much higher values for all parameters compared to the normal-appearing adjacent iniltrated tumor regions, but in both the bulk tumor and the iniltrated tumor regions, values were found to be higher than in the contralateral normal brain regions. Tumor iniltration into white matter can induce widening of white matter iber bundles, which affects the directionality of the motion of water molecules within the white matter iber bundles. Changes in the directionality of water molecules within white matter tracts can be measured with DTI. By employing at least six diffusion gradient directions, compared to three gradient directions, DWI studies enable not only the macroscopic detection and imaging of the highly anisotropic water diffusion found in white matter bundles but can also detect changes in the anisotropic motion of water (i.e., directionality) within white matter due to tumor invasion, which cause disruption of white matter bundles.275 A DTI study generates a diffusion tensor D for each image voxel, and from each D voxel value, the magnitude and directionality of water diffusion can be calculated. The magnitude is known as the mean diffusivity (MD) and is mathematically equivalent to the ADC obtained from a conventional DWI study. The directionality is known as fractional anisotropy (FA). In a 2006 publication, Stadlbauer et al.323 used DTI to retrospectively correlate changes in FA and MD with the degree of tumor cell iniltration determined histologically. Histopathologic indings of 77 MRI-guided stereotactic biopsies in 20 glioma patients were correlated with the FA and MD values found at the biopsy sites. FA was found to be inversely correlated to percent tumor iniltration and was found to be better than MD for assessment and delineation of tumor iniltration. For low tumor cell numbers as shown in Figure 17-14, the logarithmic regression lines showed a strong decrease in FA (see Fig. 17-14A) and an increase in MD (see Fig. 17-14B) followed by an asymptotic plateauing trend for high tumor cell number. From these indings, the investigators hypothesized that their indings “relect the iniltrative invasion mechanism of gliomas”—namely, initial

514

PART II CT and MR Imaging of the Whole Body

IC1

Lip and lac

g1

Cho

40

35

30

25

A

20

15

10

05

40

35

30

25

D

ppm

20

15

10

05

10

05

10

05

ppm

IC2

g2 NAA

Cho Cr

40

35

30

25

B

20

15

10

05

40

35

30

25

E

ppm

20

15

ppm

NAA IC3 g3 Cr

Cho

40

C

35

30

25

20 ppm

15

10

40

05

F

35

30

25

20

15

ppm

FIG 17-13 A-C, The three independent components (ICs) generated from the 1517 voxels, normalized as described by Wright and coworkers.368 D, The median of all absorption spectra, with IC1 as the component with the highest coeficient (g1, necrotic tumor core), illustrated with the 25% and 75% quartiles above and below (dashed lines). E and F, The median and quartiles of spectra for the highest-coeficient components of IC2 and IC3, respectively (g2 [iniltrative tumor growth] and g3 [normal brain]). D-F, Key metabolite resonances, indicated as Lip and lac (lipids and lactate), Cho (cholines), Cr (creatine), and NAA (N-acetylaspartate); g2 (E), the median and quartiles of spectra for the highest-coeficient IC2 (mixture of normal and iniltrative tumor pattern); g3 (F), the median and quartiles of spectra for the highest coeficient IC3 (normal brain pattern). (From Wright AJ, et al: Pattern recognition of MRSI data shows region of glioma growth that agrees with DTI markers of brain tumor iniltration. Magn Reson Med 62:1646–1651, 2009.)

515

Brain Proton Magnetic Resonance Spectroscopy

CHAPTER 17

2.25

0.35

2.00 MD value [x 10–3 mm2/s]

FA value

0.30

0.25

0.20

0.15

1.75 1.50 1.25 1.00 0.75

R = –0.796

0.10 0

A

20

R = 0.521 40

60

80

100

Tumor infiltration [%]

0

20

B

40

60

80

100

Tumor infiltration [%]

FIG 17-14 Scatterplot of fractional anisotropy (FA) and mean diffusivity (MD) vs. percentage TI. A, Linear regression (solid line) of FA versus percentage TI for all biopsies sampled. Regression analysis resulted in R = 0.796 and P < 0.001. Linear regression it is represented by FA = 0.28-1.5 × 10−3 percentage TI. B, Linear regression (solid line) of mean diffusivity versus percentage TI for all biopsies sampled. Regression analysis resulted in R = 0.521 and P < 0.001. Linear regression it is represented by mean diffusivity = 1.17-5.9 × 10−3 percentage TI. Dotted lines = 95% CIs. (From Stadlbauer A, et al: Preoperative grading of gliomas by using metabolite quantiication with high-spatial-resolution proton MR spectroscopic imaging. Radiology 238:958– 969, 2006.)

TABLE 17-2 Median Values of FA and MD in the Tissue-Segmented Groups g1 (Tumor Core), g2 (Iniltrative Tumor Growth), and g3 (Normal Brain) FA

MD

g1

g2

g3

g1

g2

g3

Median Signiicantly different from g1 (Mann-Whitney U test)

0.128 — —

0.240 Yes P = 3 × 10−49 No P = 0.11

1.23 (×10−3) —

Signiicantly different from g2 (Mann-Whitney U test)

0.233 Yes P = 7 × 1048−48 —

1.13 (×10−3) Yes P = 1 × 10−4 —

0.909 (×10−3) Yes P = 2 × 10−30 Yes P = 8 × 10−27

—

From Wright AJ, et al: Pattern recognition of MRSI data shows region of glioma growth that agrees with DTI markers of brain tumor iniltration. Magn Reson Med 62:1646–1651, 2009.

enlargement of the extracellular space as the tumor invades, leading to a logarithmic decrease in FA and a logarithmic increase in MD but preserving the normal microstructure of the white matter iber bundles in the border zone. This hypothesis is consistent with the data of Di Constanza et al.93 in which the NAA levels remained relatively unchanged while the Cho levels increased by almost 50% in suspected tumor-iniltrated normal-appearing ipsilateral white matter. This lack of change in NAA relects only the initial phase of tumor iniltration into these regions, which induces only mild disruption of white matter bundles. As more tumor cells iniltrate and proliferate, there is a decrease in the extracellular space (e.g., edema) and a decrease in directionality of diffusion due to tumor-induced derangement and destruction of white matter microstructures, which leads to decreases in NAA along with increased Cho levels. A number of investigators have proposed the combined use of proton MRSI and DTI to map out the iniltrative regions of gliomas.33,117 Wright et al.368 performed independent component analysis of MRSI

data from human gliomas to segment tissues into tumor core, tumor iniltration, and normal brain. DTI analysis was then used to conirm the correctness of the MRSI segmentation pattern (see Fig. 17-13). They found that the MD and FA data found for these regions were consistent with previous studies that compared anomalies in isotropic and anisotropic diffusion images to determine regions of potential glioma iniltration (Table 17-2). They showed that coeficients of independent components from their analysis could then be used to create colored images overlaid onto conventional anatomic images to visualize regions of iniltrative tumor growth. MRSI and DTI both provide markers that represent iniltrative growth, and the two techniques are complementary. DTI can detect abnormalities with high spatial resolution, and MRSI can provide validation of the presence of proliferating and/or iniltrating tumor cells from the metabolic proile. The combination of markers will provide greater certainty in correctly identifying regions of tumor iniltration, which can then be treated appropriately.

516

PART II CT and MR Imaging of the Whole Body

Monitoring Tumor Response to Therapy MRS may be able not only to facilitate diagnosis and accurate classiication of de novo brain tumors but also to allow differentiation of recurrent tumor and tumor progression from radiation necrosis, posttreatment effects, and edema.36,52,53,296 Thus MRS may be useful in evaluating the response to therapy in patients with brain tumors. Radiation necrosis occurs from approximately 6 to 24 months after completion of conventional therapy, is seen more commonly with high-grade astrocytomas, and may be indistinguishable from recurrent tumor by conventional Gd-enhanced MRI.53 Elevated Lac levels are seen in proton MR spectra of patients who have received 40 Gy or more of radiation to the brain, even when the conventional MRI study does not yet demonstrate any structural abnormality within the resection bed.53 One study involving 25 patients with cerebral astrocytomas who received a combination of radiation and chemotherapy demonstrated increased Cho/NAA and Cho/Cr ratios as well as the presence of Lac in recurrent tumors, compared to markedly decreased levels of NAA, Cho, and Cr and the presence of a broad intense signal between 0 and 2.0 ppm in cases of radiation necrosis.53,102 This broad signal, between 0 and 2.0 ppm, consists of free fatty acids, Lac, and amino acids.53,102 However, because most therapy-induced tissue damage occurs in combination with areas of viable tumor, single-voxel techniques are not optimal for evaluation of these patients, and 3D MRSI is preferable for distinguishing among areas of residual or recurrent tumor, radiation necrosis, and viable normal brain tissue.52,372 Sensitivity and speciicity of proton MRS for the detection of residual/recurrent tumor in radiated patients in one series were 71% and 100%, respectively, and serial MRS in the same series allowed differentiation of necrosis and tumor progression; progressive decreases in Cho levels and mild increases in NAA levels correlated well with therapy success.52,333 Elmogy et al.99 in a 23-patient study with 2D MRSI found that Cho/ NAA ratios were the best discriminators of recurrent/residual tumor from radiation injury. In this study using a cutoff of 1.8 for the Cho/ NAA ratios, an accuracy of 96%, a sensitivity of 93%, and speciicity of 100% were found. In a 3D MRSI of 28 patients, Zeng et al.,372 using a cutoff of 1.71 for either Cho/Cr or Cho/NAA, resulted in a ROC analysis of 96.2% for accuracy, 94.1% for sensitivity, and 100% for speciicity of MRSI in discriminating recurrent/residual tumor from radiation injury. Tedeschi and coauthors demonstrated that interval changes in Cho levels during long-term (3.5 years) follow-up with MRS allowed differentiation of stable from progressive glioma.36,336 A study by Henry et al. suggested that MRS and MR perfusion imaging (namely, rCBV mapping) may be complementary modalities that when combined may be better able to noninvasively differentiate tumor from necrosis, posttreatment effects, or edema in patients with treated gliomas than either modality alone.134 Graves et al.126 examined 18 patients with recurrent malignant gliomas with proton MRSI to characterize the temporal tissue responses in these tumors after receiving high-dose gamma knife radiosurgery treatment. Only six patients with recurring high-grade gliomas responded to the treatment and showed reduction of Cho and an increase in Lac/lipid resonances, typically within 6 months post treatment. Of the 18 patients treated with radiosurgery, 12 recurred after treatment (recurrence was deined as > 2 cc increase in Gd contrastenhancement areas). In each case, an elevated Cho/NAA ratio was associated with at least one voxel within the area of recurrence. In 9 of the 12 recurring patients, voxels coinciding with the recurring regions showed increased Cho/NAA ratios relative to normal-appearing voxels

prior to increases in contrast enhancement. In the remaining 3 patients, the new areas of contrast enhancement appeared in regions and were characterized by pronounced increases in Cho/NAA ratios. Other groups have reported similar success in distinguishing radiation necrosis from recurrent tumor with proton MRS, although a few have reported contradictory results; the reasons for differences in results may be due to the fact that Cho levels may be elevated in early radiation-induced lesions because of demyelination and reactive astrocytosis.62,68,79,161 In addition, Bizzi and coworkers reported that MRS is useful in the surveillance of lymphoma following treatment.35,52

Role of Proton MRSI in Predicting Tumor Prognosis Long-term prognosis for patients with HGG remains dismal even with advances in both imaging and therapy. In a 2003 survival analysis of 766 GBM patients, only 2% of these patients were found to be still alive after 5 years.224 Given such a bleak prognosis, there is a need to identify noninvasive biomarkers that can be used to characterize individual lesions and predict outcome. This information can then be used to stratify patients into high- or low-risk categories to determine which patients may beneit from new and/or experimental therapies. Several studies have evaluated the role of proton MRSI in the prediction of survival of GBM patients.61,80,303 In a multiparametric MR study of 56 GBM patients, proton MRSI, conventional MRI, DWI, and PWI were combined to examine whether pretreatment characteristics of the tumors obtained from these studies could be used to predict survival of these patients after treatment.80 This study showed that shorter survival was associated with the volume of tissue with abnormally high Cho/NAA ratio [CNI > 2; (Cho/NAA)tumor vol/ (Cho/NAA)normal contralateral vol], contrast-enhancing tissue and high rCBV, and tissue with abnormally low ADC values. Higher Lac and level of lipids were also associated with a worse prognostic outcome. Several studies have also examined the prognostic value of proton MRS in evaluating pediatric brain tumors. In a study of 76 pediatric brain tumors, a low Cho/Cr ratio—less than 1.8 index value (normalized to contralateral Cr peak area)—was found to be a strong predictor of survival.216 In a different report, a high Cho/NAA ratio in children with recurrent gliomas was associated with decreased survival.361 In a multiparametric longitudinal MRI study of 34 patients conducted at the National Cancer Institute (Bethesda, Md.), Hipp et al. used proton MRS, conventional MRI, and perfusion MRI data to predict outcome in children with diffuse intrinsic pontine gliomas.139 They found that at baseline MRI only, increased ratio of Cho/NAA and increased perfusion on dynamic susceptibility contrast (DSC)-MRI predicted shorter survival. When examined at later time points, any volumes with an observed maximum Cho/NAA ratio on MRSI (i.e., >4.5) or increased Cho/NAA on either single- or multivolume MRSI compared to baseline increased perfusion, and the presence of enhancement predicted shorter survival. They concluded that changes in Cho/NAA over time, as determined by either single- or multivolume MRS were “prognostic and can potentially be used as indicators of response or lack of response to treatment.” They also recommended that routine baseline and subsequent imaging for children with diffuse intrinsic pontine gliomas should, at a minimum, incorporate both DSC-MRI and single-voxel spectroscopy.

Differentiation of Neoplastic from Pseudotumoral Process The differential diagnosis of a brain lesion may vary depending on its solid and necrotic characteristics. For example, if the brain mass encountered on a conventional MR examination appears more necrotic in nature, the differential diagnosis would favor that of either an

CHAPTER 17

Brain Proton Magnetic Resonance Spectroscopy

aggressive malignant brain tumor (e.g., metastatic brain lesion or GB) or nonneoplastic pseudotumoral brain lesion that mimics a brain tumor (e.g., abscess, tuberculous granuloma, parasitic infection, or radiation necrosis if the patient had received radiation treatment for a brain tumor). Conversely if a brain lesion appears solid on the MRI the main diagnosis would be either an HGG or a pseudotumoral demyelinating disease process such as multiple sclerosis. MRI examination suggesting a pseudotumoral nonneoplastic process would lead to further clinical tests to determine the type of process so that the appropriate therapy could be applied. However, if a neoplastic process is suggested from the MRI exam, then a stereotactic biopsy or surgical resection would be considered to determine whether the lesion is an HGG or metastatic lesion and used to determine whether further chemotherapeutic and/or radiation therapy treatments are needed. However, in many cases reliable differentiation of neoplastic from nonneoplastic brain lesions cannot be unequivocally made from conventional MRI.184,256 Proton MRS can help differentiate between brain tumors and nonneoplastic brain lesions.46,237,269,282 In two retrospective studies, discriminant function analysis using proton MRSI data correctly classiied 78% of pediatric cases with primary brain lesions based on Cho/Cr ratio (the study included 32 subjects).147 In 69 adult patients with untreated primary brain lesions, proton MRS imaging correctly classiied 84% of originally grouped cases based on NAA/Cho, NAA/ Cr, and relative NAA and Cho levels (compared to the contralateral

hemisphere). Combining proton MRSI and perfusion MRI, sensitivity of 72% and speciicity of 92% were achieved using cutoff points corresponding to the diagnosis of tumor of 0.61 for the ratio of NAA/Cr and 1.5 for rCBV.146 Recently the role of routinely used advanced MRI in differentiation of intracranial masses in adults was evaluated5 and the accuracy of an MRI-based strategy to differentiate among histologically conirmed neoplastic and nonneoplastic lesions was assessed. This review and assessment led to the development and evaluation of a MR-based decision paradigm that could be used to differentiate neoplastic from nonneoplastic processes.6 This “practical MRI-based” paradigm proposed in Figure 17-15 used results from postcontrast Gd-enhanced, DWI, PWI, and multivoxel H1-MRSI with well-deined thresholds to determine how well this multiparametric approach could not only accurately differentiate neoplastic from nonneoplastic lesions but also classify the type of neoplastic lesion (e.g., glioma from lymphoma and metastatic lesions) and nonneoplastic processes (e.g., abscess from tumefactive process).55 The MR-based diagnostic paradigm was evaluated in 40 patients who had complete data from all MR techniques to differentiate between tumors and nonneoplastic pseudotumoral processes. The accuracy, sensitivity, and speciicity of the paradigm using the threshold values used in the ROC curves for each technique was found to be 90%, 97%, and 67%, respectively. For discrimination of high-grade from low-grade gliomas, the accuracy, sensitivity, and

Intraaxial brain mass

Conventional CE MRI Does the lesion enhance? Yes

No

Magnetic Resonance Spectroscopy Is there elevation of Cho/NAA over 2.2?

Diffusion MRI Is diffusion facilitated over 1.1/100mm2/ADC?

Yes

No

Yes

No

Low-grade neoplasm or Encephalitis

Is there necrosis on CE MRI? Perfusion MRI Is perfusion increased over 1.75 rCBV? No

Low-grade neoplasm

No

Yes No

Yes

Lymphoma

Yes

High-grade neoplasm

TDL or abscess Abscess

Magnetic Resonance Spectroscopy Is there perienhancement infiltration over 1 Cho/NAA? No

Metastasis

517

Yes

High-grade glioma

FIG 17-15 Flow chart for determining brain lesion type based on conventional contrast-enhanced MRI, DWI, MRS, and PWI. 1.1/100mm2/ADC, 1.1 × 10−3 mm2/sec; ADC, apparent diffusion coeficient; CE, contrastenhanced; rCBV, relative cerebral blood volume; TDL, tumefactive demyelinating lesion. (Modiied from AlOkaili RN, et al: Intraaxial brain masses: MR imaging–based diagnostic strategy–Initial experience. Radiology 243:539–550, 2007.)

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speciicity was 90%, 88%, and 100%, respectively, and 85%, 84%, and 87% for discrimination of high-grade tumors and lymphomas from low-grade tumors and nonneoplastic pseudotumoral processes. The results of this paper clearly indicate that integration of advanced complementary MRI techniques with conventional anatomic MRIs can improve the diagnosis and classiication of brain lesions, which in turn will add value to the clinical decisions being made for patients with these types of lesions (see Fig. 17-15). Typically, tumors exhibit elevated Cho and decreased levels of NAA. The greatest beneit of adding MRS to a clinical examination may be to exclude processes in the diagnosis that have markedly different spectral characteristics but similar MRI characteristics to a low-grade tumor such as focal cortical dysplasias or strokes. Neither of these latter two lesions show elevated Cho levels but show decreased levels of NAA.196,360 Similarly, spectra from brain abscesses are quite different from HGGs, but the anatomic MRI appearance is similar to necrotic malignant tumors, especially GBs.189 However, the MR spectral proiles of abscesses compared to high-grade tumors normally show decreased Cho, NAA, and Cr resonances and increased resonances from compounds not normally observed in brain tumors, such as alanine, acetate, acetoacetate, and succinate. Another application of proton MRS is the differentiation of gliomas from hamartomas, particularly in the setting of phakomatoses such as neuroibromatosis type 1.296 NAA/Cho, NAA/Cr, and Cr/Cho ratios in hamartomas are closer to those of normal brain tissue than to those of gliomas; speciically, studies have demonstrated Cho/Cr ratios greater than 2.0 in gliomas, between 1.3 and 2.0 in hamartomas, and less than 1.3 in normal brain tissue.48,119,296

Metastases Brain metastases are the most common intracranial tumors in adults in 20% to 40% of cancer patients,12,270 although they usually do not pose much of a diagnostic challenge when multiple brain lesions are observed on conventional MRI. However, metastases can be problematic when they are solitary, because it may be dificult to distinguish them from primary brain neoplasms.42 Unfortunately, proton MR spectra of intracranial metastases are often nonspeciic and indistinguishable from those of primary brain tumors; at long TE, they display low NAA levels, low Cr levels, and elevated Cho levels as shown in Figures 17-16 and 17-17.51-53,150,183,252 Although in theory NAA should not be present in metastases because of their lack of neural components, NAA is frequently present in proton MR spectra, presumably secondary to voxel contamination with adjacent brain parenchyma or due to the presence of N-acetylated metabolites on their cell membranes.52 One study indicated that although no statistically signiicant difference existed between signal areas of Cho, Cr, and NAA in the spectra of metastases and those of high-grade astrocytomas, a trend toward higher Cho/Cr and Cho/NAA ratios in astrocytomas did exist, and lipid and Lac signals were more common in intracranial metastatic lesions.52 Lipid signals are often present in metastases, particularly those from breast carcinoma.53,318 Detection of an enhancing brain lesion on conventional crosssectional imaging invokes a much broader list of malignant and benign differential considerations. In fact, as many as 11% of solitary brain lesions identiied on MRI may represent processes other than metastases.260 In these cases, adjunctive tests such as proton MRS and PWI can be helpful both in distinguishing malignant from benign lesions and in differentiating primary brain tumors from metastases.150,191 Malignant brain tumors tend to demonstrate both high Cho and increased vascularity compared to benign processes. Huang et al.150 found a very strong positive association between Cho/Cr ratios and rCBV in brain metastases. Law et al.191 showed that both Cho/Cr levels

and rCBV remain relatively higher in the peritumoral region (1 cm from enhancing margin) in GBMs compared to the uninvolved contralateral region, whereas in metastatic peritumoral regions, both Cho/ Cr levels and rCBV are near normal compared to the contralateral uninvolved regions. Metastatic lesions compared to primary malignant brain tumors show a more circumscribed lesion with almost normal peritumoral Cho/Cr ratios compared to high-grade primary brain tumors (Fig. 17-18; compare with Fig. 17-11).

Other Tumors MRS indings in gliomatosis cerebri include elevated Cho/Cr and Cho/ NAA ratios as well as varying degrees of decreased NAA/Cr ratios.30 A maximum Cho/NAA ratio of 1 : 3 was detected in low-grade lesions, compared with 2.5 for anaplastic tumors; in addition, Lac signals were noted in grade III and IV lesions.30 MR spectra of acoustic schwannomas show absence of Cr, marked reduction in NAA, and increased lipids.43,52 Other MRS studies have attempted to distinguish astrocytomas from ependymomas and primitive neuroectodermal tumors (PNETs); these studies have demonstrated reduced NAA/Cho and elevated Lac/Cho ratios in astrocytomas and ependymomas in comparison with PNETs.296,327,328,345,357 Meningiomas have also been extensively studied with proton MRS, and they display certain characteristic features on MR spectra. Marked elevation of Cho levels up to three times that of normal brain parenchyma have been reported, particularly in recurrent menigiomas.52,53,183 The Cho/Cr ratio has been reported to be higher in malignant meningiomas than in benign menigiomas.52,252

Traumatic Brain Injury Recent studies of concussion have revealed how complex this often misdiagnosed condition can be. A single episode of traumatic brain injury (TBI), induced by the mechanical trauma of acceleration and deceleration forces on the brain, can set off a cascade of complex neurochemical and neurometabolic brain processes23 that, depending on the severity of the TBI, can be either reversible or irreversible. Rotational forces from TBI can lead to axonal stress and strain, causing diffuse axonal injury (DAI).219 After the initial brain insult, a destructive series of biochemical processes occur, such as activation of inlammatory responses, imbalances in Na+, K+, and Ca+2 ion levels, increases in the presence of excitatory amino acids, dysregulation of neurotransmitter synthesis, and increased production of free radicals.363 As a result of these responses to the brain insult, individuals present with myriad of clinical symptoms.47 What is more disturbing is that in 15% of individuals diagnosed with mild TBI (mTBI) report physical, cognitive, and emotional symptoms that persists for more than 1 year post injury.175,366 These persistent symptoms can lead to postconcussive syndrome and long-term disabilities. Despite the cascade of destructive pathophysiologic and biochemical processes that occur after MTI and especially mild brain injuries, conventional neuroimaging techniques (i.e., CT and MRI) and neuropsychological tests (i.e., Glasgow Coma Score and Glasgow Outcome Score) fail to be sensitive or speciic enough to detect changes in the early subacute phase of injury and also in individuals who have had previous mTBI.8 Recently, advanced MRI techniques (i.e., SWI, DTI) and multivolume H1-MRS imaging have emerged as promising techniques that can more accurately assess the severity and regional distribution of injury. Complimentary data obtained from these techniques can then be used to obtain reliable metrics to predict the severity and outcome after a TBI event. Accurate early prediction of a patient’s long-term prognosis enables the physician to determine appropriate treatment paradigms.9

CHAPTER 17

Brain Proton Magnetic Resonance Spectroscopy NAA I : 0.136

0.020

Cho I : 0.134 Met. NSCL Ca: Cho/Cr > 2.0

0.015

0.010 Cr Cr2 I : 0.0170 I : 0.103 0.005

0.000

ppm

A

3

2

1

Cho I : 3.77 0.5

CSI VOXEL MET BREAST CA Cho/cr > 2.0

0.4

0.3

0.2 Cr I : 0.845 NAA I : 0.608

0.1

0.0 ppm

B

3

2

1

FIG 17-16 A, Metastatic non–small cell lung cancer spectrum. B, Metastatic breast cancer. Continued

519

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PART II CT and MR Imaging of the Whole Body

0.20 MET MELANOMA

0.15

0.10

NAA I : 1.05

Cr I : 0.763 0.05

0.00 ppm

C

3.5

3.0

2.5

2.0

1.5

1.0

FIG 17-16, cont’d C, Metastatic melanoma.

Ratios of Cho/Cr, NAA/Cr, and Cho/NAA for different cancer types Breast

Lung

Melanoma

Mixed

Control

5

4

3

2 2.814

2.821

3.054

3.063

2.815

1

2.851

1.959 1.44

1.109

1.09

1.408

1.191 1.241

1.514 0.576

0 NAA/Cr

Cho/Cr

NAA/Cr

FIG 17-17 Metabolic ratios for different metastatic tumors.

In the case of MRS, using either single- or multivolume MRSI technique, studies have found consistently large increases in Cho/Cr ratios and diffuse decreases in NAA/Cr and NAA/Cho ratios in the brains of TBI patients.9,120,218 In a pediatric TBI patient study, Aswal et al.9 compared the differences between the acutely determined MRS variables (metabolite ratios and presence of Lac) and 6- to 12-month

outcomes. They found that the metabolite levels of NAA/Cr and NAA/ Cho were signiicantly lower in patients with poor outcome. Lac was evident in 91% of infants and 80% of children with poor outcomes. At best, using the standard clinical criteria alone predicted the outcome in 77% of the infant cohort and 86% of the children cohort. The presence of observable Lac alone predicted an outcome in 96% of both the

CHAPTER 17

Brain Proton Magnetic Resonance Spectroscopy

521

Cho/Cr

A

B FIG 17-18 Metastatic melanoma. A, Spectral map of metastatic melanoma. Note that tumor spectral pattern does not extend more than 1 voxel from Gd-enhancing rim. B, Metabolic map of metastatic melanoma. Note that Cho/Cr ratios greater than 1.5 do not extend more than 1 voxel beyond Gd-enhancing rim.

infant and children cohorts. In an MRS study conducted in adults, Marino et al.218 found similar results. Both the decrease in NAA/ metabolite ratio and the presence of Lac correlated closely with the Glasgow Coma Scale and the Glasgow Outcome Scale at 3 months. Again as in the pediatric study, the presence of detectable MRS levels of Lac is associated with poorer clinical outcome. In an H1-MRS study of clinically asymptomatic athletes recovering from single and multiple mTBIs, Johnson and colleagues163 evaluated the NAA/Cho, NAA/Cr, and Cho/Cr ratios in two regions within the corpus callosum, the genu and splenium. These two regions were chosen because the corpus callosum is a major site of TBI.321 The major inding in this study was that a single concussive episode, whether it was an initial or subsequent injury, produced signiicant reductions in NAA/Cho and NAA/Cr ratios in the genu of the corpus callosum but not in the splenium for mTBI subjects. In addition, there does not appear to be any further reduction in NAA ratios in the genu or splenium as a result of an increase in the number of mTBI episodes. However, they observed that as the number of mTBIs increased, so did the length of time for symptom resolution. The changes observed in a DTI study of the corpus callosum of mTBI patients supports the MRS indings that mTBI induces changes primarily in the genu of the corpus callosum, with little alterations in the splenium.297 Patients with mTBI examined less than 3 months post trauma, compared to controls, had reduced FA and increased MD. However, patients with moderate to severe TBI examined at less than 3 months post trauma had reduced FA and increased MD in the genu and reduced FA in the splenium, without signiicant change in the MD. This suggests a larger contribution of vasogenic edema in the genu than in the splenium in TBI.

Epilepsy Proton MRS has a major clinical application in the localization of subtle epileptogenic foci that are not evident on conventional structural MRI sequences at 1.5 T or 3 T, as well as in the planning

of epilepsy surgery. Single-voxel MRS may conirm a structurally abnormal epileptogenic focus, whereas MRSI may detect foci that appear normal on conventional structural MRI but demonstrate deinite metabolic abnormalities, such as those associated with very subtle malformations of cortical development.77,248 One study suggests that the sensitivity of MRS for detecting subtle neuronal dysfunction is greater than that of PET.2,296 Development of different surgical approaches to epilepsy, as well as the potential for future less invasive treatment modalities such as gamma knife radiosurgery, has made precise localization of seizure foci critical.14,248 Most of the applications of MRS in epilepsy have involved temporal lobe epilepsy (TLE), the most common type of partial epilepsy. Many cases of TLE are refractory to medical therapy and thus MRS can play an important role in presurgical planning in these patients.36 The most common lesion associated with TLE is mesial temporal sclerosis (also called hippocampal sclerosis), noted in approximately 65% of cases of TLE.17,36,77 Although in classic cases of mesial temporal sclerosis the involved hippocampus is easily identiied by a combination of volume loss and signal hyperintensity on T2-weighted and luid-attenuated inversion recovery (FLAIR) sequences, 20% of patients with TLE have normal structural MRI scans, and the indings in children generally tend to be more subtle than those in adults.248,296 NAA, NAA/Cho, NAA/Cr, and NAA/(Cho + Cr) all are decreased in atrophic hippocampi as well as in nonatrophic hippocampi with abnormal electroencephalographic (EEG) indings, according to the results from the series by Ende and coworkers.36,101,187 Even when seizure onset and structural MRI abnormalities are clearly unilateral, MRS has shown that bilateral temporal lobe abnormalities are present; bilateral metabolic abnormalities are found in approximately 40% to 50% of TLE patients, and in such cases these abnormalities appear to be more diffuse than the corresponding structural MRI abnormalities would suggest.76,77,83,101,137,250 Kuzniecky and colleagues argued that the lack of correlation between structural hippocampal volume loss and proton MRSI

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PART II CT and MR Imaging of the Whole Body

metabolic abnormalities relects the presence of distinct pathophysiologic processes that are coexistent in cases of mesial temporal sclerosis.186 Gadian and colleagues, examining a mixed group of patients with partial seizures, mostly with TLE, reported a 9% decrease in the NAA content of the epileptogenic temporal lobe, with an increase of 14% and 17% in the levels of Cr and Cho, respectively, suggestive of gliosis.111,174,245 Multivoxel MRS studies have shown not only reduced NAA levels in the diseased hippocampi but also the presence of Lac signals in the spectra of epileptogenic foci when studied within 6 hours of seizure activity.58,73,250,296 The postictal Lac signal has been described as having potential lateralizing value, because only one side demonstrates a signal in Lac, even in patients with bilateral disease.73 Cendes and associates noted that correct lateralization of the seizure focus in patients with TLE was possible in 83% of cases in their large series with MR volumetry and 86% with MRSI.59,174 Ende and coauthors found that the NAA/(Cho + Cr) ratio was the most sensitive measure for lateralization compared with ictal EEG.101,174 They also noted that in unilateral TLE, the reduced levels of NAA in the hippocampus contralateral to the atrophic one predict poor clinical outcome following surgical resection of the epileptic focus.36,101 Thus MRS may provide important prognostic as well as diagnostic information. MRS has also shown promise in evaluating patients with extratemporal epilepsy, including those with neocortical epilepsy. This class includes the second largest group of patients with complex partial seizures refractory to medical therapy—those with frontal lobe epilepsy.1 Garcia and coworkers113 reported that in a series of eight patients with frontal lobe epilepsy, the mean NAA/Cr ratio in the epileptogenic frontal lobe was decreased by 27% compared with that of the contralateral frontal lobe, with decreases of at least 5% in each individual.1 In addition, in patients with structural MR evidence of malformations of cortical development or neuronal migration disorders (NMD), MRS provides insight into both the pathophysiology and the true spatial extent of the disease processes. Li and coworkers showed that the maximal NAA/Cr ratio decrease, indicative of metabolic dysfunction, localized to the structural malformation noted on conventional MRI in 23 cases of malformations of cortical development (including focal cortical dysplasia, heterotopia, polymicrogyria, and tuberous sclerosis)198; however, less impressive decreases also extended to normal-appearing areas of brain tissue adjacent to the structural lesion. Simone and colleagues, in their series of 15 patients with NMD, noted abnormally decreased NAA/Cr and Cho/Cr ratios in these lesions when compared with gray and white matter of neurologically normal controls319; they also noted abnormally decreased Cho/Cr ratios in the normal-appearing brain contralateral to the identiied NMD compared with gray and white matter of controls. The absence of correlation between the NAA/Cr decrease, EEG abnormalities, and NMD lateralization suggested that the metabolic abnormality may be related more to the underlying structural and functional alterations within the focus of NMD than to actual epileptic activity in the lesions, and that the Cho/Cr ratio decreases may relect more extensive diffuse hypomyelination than what the structural MRI suggested.319 H1-MRS can be combined with phosphorus 31 MRS (31P) to conirm the metabolic changes observed in the H1-MRS studies in epilepsy patients to identify the location(s) of the seizure foci. These studies have shown ictal increases in inorganic phosphorus (Pi) and Lac and decreases in phosphocreatine (PCr) levels and pH as measured by P31-MRS in TLE.174,313,369 Postictally, pH was noted to increase with development of alkalosis before Lac normalization.174,317 In addition, ipsilateral

increased Pi and decreased phosphomonoester (PME; phosphocholine and/or phosphoethanolamine) levels without signiicant differences in other metabolites have been noted in TLE.152 Kuzniecky et al. have found in their study of patients with TLE that the PCr/Pi ratio was reduced by 50% in the epileptogenic temporal lobe compared with controls and by 35% when compared with the unaffected contralateral temporal lobe185; in their study, however, they did not observe any signiicant differences in intracellular pH between controls and patients.185

Alzheimer’s Disease Alzheimer’s disease is the most common form of dementia in older adults and represents approximately 40% to 60% of all dementias.36,53 The disease is characterized by decreased cortical acetylcholine, neuronal loss, amyloid deposits, and neuroibrillary tangles. Diagnosis, which may be dificult, is based primarily on clinical criteria, and imaging has been used mostly for excluding other possible causes of dementia such as intracranial mass lesions and subcortical vascular disease. Nevertheless structural MRI can conirm clinical indings in Alzheimer’s disease by demonstrating preferential atrophy of the hippocampi and temporoparietal cortex. Proton MRS, however, may enable earlier diagnosis of this disease.253,287,288 The proton MR spectrum in Alzheimer’s disease demonstrates an abnormally elevated MI/Cr ratio and an abnormally decreased NAA/Cr ratio.168,232,235,236,291,314 This combination of spectroscopic indings distinguishes Alzheimer’s disease from normal conditions in the elderly,168,314 whereas the elevated MI/Cr ratio distinguishes Alzheimer’s disease from other dementias, with the possible exception of Pick’s disease.291 Reduced levels of NAA in Alzheimer’s disease are noted in the frontoparietal regions, temporal lobes (including hippocampi), and posterior cingulate region.36,168,305,334 In Pick’s disease, however, decreased NAA levels and elevated MI levels are noted in the frontal lobes. Because no such similar metabolic abnormalities are present in these brain regions in those with Alzheimer’s disease, the differentiation between Alzheimer’s and Pick’s disease can be made on the basis of proton MRS indings. More than 90% of cases may be correctly classiied based on these differences in MRS indings.36,103 However, many confounding metabolic disorders can also result in abnormal MI/Cr ratios; renal failure, diabetes mellitus, chronic hypoxic encephalopathy, and hypernatremia can all result in elevated MI concentrations, whereas hepatic encephalopathy and hyponatremia can result in decreased MI concentrations.179-181,194,230,291,352

Degenerative and Metabolic Brain Disorders Various metabolic disorders, including primary leukodystrophies and mitochondrial disorders, have been studied with proton MRS. Although the MRS indings, conventional MRI indings, and clinical symptoms of most of these degenerative brain disorders (many of which present in childhood) are nonspeciic, MRS can sometimes be useful in distinguishing the various clinical entities. Wang and Zimmerman have divided brain metabolic disorders into ive general categories359: 1. Disorders of lipid metabolism 2. Disorders of carbohydrate metabolism and respiratory chain 3. Disorders of amino acid metabolism and the urea cycle 4. Primary white matter disorders 5. Miscellaneous metabolic disorders not itting into the previously described categories Peroxisomal and mitochondrial disorders may be considered to be subcategories of these ive categories.359 Disorders of lipid metabolism include the following359:

CHAPTER 17 •

Brain Proton Magnetic Resonance Spectroscopy

Abnormalities of long-chain fatty acid metabolism (peroxisomal diseases), such as Zellweger’s syndrome (in which peroxisomes are deicient or absent) • Rhizomelic chondrodysplasia punctata (in which several peroxisomal enzymes are absent) • Adrenoleukodystrophy (ALD) (in which a single peroxisomal enzyme is deicient) ALD is unique in that among hereditary leukodystrophies it is the only one associated with an increased Cho signal at times other than during the early stage of acute demyelination.36 In childhood ALD, decreased NAA/Cr ratio and increased Cho/Cr ratio are present in addition to elevated Lac, Glu, Gln, and MI signals in the white matter lesions.53,343 A recent quantitative study performed at 4 T identiied seven metabolites as markers of lesion development. Of these metabolites, NAA, Gln, and [lipids + Lac] were the strongest markers.254 The decline in the NAA/Cr ratio in X-linked ALD both parallels disease progression and can predate the emergence of white matter hyperintensities on conventional T2-weighted MRI scans.74,309 Elevated Cho and reduced NAA have been reported in normal-appearing white matter in ALD patients.182,300 Reduction in NAA/Cho in normalappearing white matter on conventional MRI may be suggestive of the onset of white matter degeneration and may predict lesion progression.98 Disorders of carbohydrate metabolism include diabetes mellitus and galactosemia. In diabetes mellitus, MRS reveals elevated glucose signal and an acetone signal at 2.2 ppm, owing to hyperglycemia and ketogenesis.180,294 It is suggested that the extent of brain injury in severe diabetic ketoacidosis may be evaluated with MRS, because elevated Lac levels have been noted in individuals who eventually die of cerebral herniation and cardiac arrest.359 Increased glucose levels are observed in patients with type 1 diabetes, recurrent hypoglycemia, and hypoglycemia unawareness.81 No difference in brain glucose concentration was detected between patients with poorly controlled diabetes and healthy volunteers evaluated at the same concentrations of plasma glucose.307 In galactosemia, a condition in which one of various inborn errors of metabolism prevents normal conversion of galactose to glucose, neonates demonstrate elevated brain galactitol signals in proton MR spectra at 3.67 and 3.74 ppm at the time of symptom onset; this corresponds to elevated levels of galactitol in brain autopsy specimens in fatal cases.355,356,362 Disorders of the respiratory chain include mitochondrial disorders such as mitochondrial myopathy, encephalopathy, lactic acidosis, and strokes (MELAS) and myoclonic epilepsy with ragged red ibers (MERRF), Kearns-Sayre syndrome, and pyruvate dehydrogenase deiciency (PDD). MRS may provide useful information regarding the extent of metabolic derangement, severity of disease, and response to therapy.91,133,173,359 All these diseases are characterized by brain Lac accumulation secondary to impaired mitochondrial oxidative phosphorylation.359 However, MRS may not detect elevated CNS Lac in all cases.88 Presence of elevated Lac in the spectrum may be affected by differences in types and severity of mitochondrial disorders, timing of the scan with respect to the course of the disease, and selection of examined brain region with respect to the affected brain tissue.203 MRSI is the preferred approach for evaluating distributions of cerebral metabolites in these disorders because the distribution of Lac in the brain may vary signiicantly across different anatomic regions and because metabolic abnormalities may be present even when no corresponding conventional brain MRI abnormalities are detected.50,213 Typically the most striking Lac elevations are noted in regions of brain displaying the most marked structural abnormalities on conventional MRI. Elevated Lac has been noted in the parietooccipital gray and white matter in MELAS; occipital cortex in MERRF; brainstem, basal ganglia, and

523

occipital cortex in Leigh’s syndrome; and cortical gray matter in Kearns-Sayre syndrome.296 All these syndromes are also associated with decreased NAA/Cr ratios, presumably related to neuronal loss or dysfunction.127,213 However, PDD has been associated with more marked reductions in NAA/Cr ratios in addition to elevated Lac levels and decreased Cho/Cr ratios309,359,374; Zimmerman and Wang have noted one case in which NAA was completely absent from the spectrum.309,359,374 Disorders of amino acid metabolism include entities such as phenylketonuria (PKU), the most prevalent of this class of disorders, and maple syrup urine disease (MSUD). PKU results from a deiciency of the hepatic enzyme phenylalanine hydroxylase and demonstrates an autosomal recessive mode of inheritance.306 In patients with PKU, the proton MR spectra are remarkable only for an abnormal elevation of the phenylalanine signal at 7.3 ppm, which is speciic for this disease.359 In patients with MSUD, long TE proton MR spectra reveal a signal at 0.9 to 1.0 ppm in addition to a reversible decrease in the NAA/Cr ratio during acute metabolic decompensation.106,358,359 Abnormal accumulation of valine, leucine, and isoleucine occurs in the CSF, blood, and tissues as a consequence of defective oxidative decarboxylation.94,359 Ornithine transcarbamylase deiciency is the most common disorder of the urea cycle and is inherited in an X-linked dominant fashion. In patients with this condition, hyperammonemia and intracerebral Gln accumulation lead to cerebral edema, neuronal loss, and white matter gliosis.176,359 Reported MRS abnormalities include elevated Gln levels in a case of hyperammonemia, and decreased MI with a normal Gln level in one patient with a normal serum ammonia level.75,294 The primary white matter disorders include Canavan’s disease, Alexander’s disease, and Pelizaeus-Merzbacher disease, among others.20 In patients with Canavan’s disease, which is the only primary white matter disorder with truly speciic indings on MRS, markedly increased NAA levels have been noted, probably secondary to impaired NAA breakdown related to a deiciency in the enzyme aspartoacyclase.36,53,127,210 Canavan’s disease is the only metabolic disorder associated with an elevated NAA level.358,359,367 Other indings in Canavan’s disease include elevated MI levels and decreased Cho and Cr signals; the decreased Cho is probably due to failure of myelination, whereas a decreased Cr level may relect spongy degeneration.359 In patients with Alexander’s disease, decreased NAA levels and elevated Lac levels are observed, most prominently in the frontal lobe; the structural white matter abnormality extends from the frontal lobes posteriorly.127,359 Pelizaeus-Merzbacher disease has been characterized by normal spectra or slight decreases in NAA in the basal ganglia in the early stages and by more prominent NAA decreases and Cho increases in advanced disease.127,190 In contrast, a recent single-voxel proton MRS study of ive patients with genetically proven PelizaeusMerzbacher disease showed increased concentrations of NAA, Gln, MI, and Cr and decreased Cho in affected white matter.239 It was concluded that the observed spectroscopic pattern, suggesting increased neuroaxonal density, astrogliosis, and reduction of oligodendroglia, was consistent with the histopathologic characteristics of dysmyelination and hypomyelination.239 Several as-yet unclassiied primary white matter diseases have also been reported. For example, van der Knaap and coauthors348 have reported a new leukoencephalopathy in nine children, manifested by severe white matter degeneration with elevated Lac and Glu and virtual disappearance of most other metabolites in MR spectra.359 A leukoencephalopathy associated with an inborn error of metabolism of the polyols arabinitol and ribitol (resonance signals in the range 3.5-4.0 ppm) was described recently.239 Tedeschi and associates have

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PART II CT and MR Imaging of the Whole Body

described a new white matter syndrome resulting from a metabolic defect producing hypomyelination and secondary axonal dysfunction characterized by a prominent decrease in NAA, Cho, and Cr levels and an increase in Lac.36,337 In general, childhood demyelinating disorders and neuronal degenerative disorders typically demonstrate decreased NAA/Cr ratios, with the degree of decrease corresponding to the extent of white matter disease and degree of cortical atrophy, respectively, depicted on conventional MRIs.53,351 Decreased NAA levels and elevated Lac levels are noted in Schilder’s and Cockayne’s diseases in addition to the disorders described earlier.53,127 Miscellaneous metabolic disorders not itting into the previously described categories are characterized by speciic pathologic changes in proton MR spectra. For example, abnormal lipid signals are seen in Niemann-Pick disease type C (a lysosomal disorder), low Cr levels are present in guanidinoacetate methyltransferase deiciency, and elevated Gly levels are present in nonketotic hyperglycinemia.295,325 In hepatic encephalopathy, increased levels of Glx (due to increased concentrations of Gln) and decreased levels of MI and Cho in proton MRS have been described; the Gln elevation is thought to be secondary to hyperammonemia.292,359 MRS may even be able to detect subclinical encephalopathy, in that the reduction in MI level may occur even in patients with hepatic disease without neurologic symptoms.53,181,293 The speciicity of these abnormalities may be useful in both diagnosis and monitoring of therapeutic eficacy in these conditions.

Stroke Stroke is another clinical condition in which MRS has been used. Its utility in the acute stroke setting is less than that of DWI, PWI, or even noncontrast CT, because rapid imaging is critical in the hyperacute and acute settings for decision making regarding need for thrombolysis. However, proton MRS may be useful in the chronic phase248 for assessing prognosis and monitoring recovery from stroke.248,258,259,263 MRS has also been an important research tool for evaluating the mechanisms of ischemic damage to brain tissue.251,320 The irst detectable change in the MR spectrum that occurs following the onset of cerebral ischemia is the appearance of the Lac doublet.286 The Lac signal has been noted within minutes of induction of ischemia in animal models, and its level tends to rise over the irst few hours after onset.3,32,238,242,286 A blood low threshold of 20 mL/100 g of brain tissue per minute has been described in animal models for the appearance of Lac, but whether a similar threshold exists for humans is not certain.82 Studies in humans have also noted the presence of Lac during the irst few days following symptom onset, correlated with ischemia and resultant edema.19,248,360 Not only does MRS demonstrate spectral changes before comparable changes in signal intensity of ischemic tissue on conventional T2-weighted MRIs occur, but also the extent of cerebral tissue displaying metabolic abnormalities exceeds the extent of signal hyperintensity on the T2-weighted images.19,120,242,286 In addition, the concentration of Lac in ischemic tissue is not homogeneous; rather, the center of the infarct tends to demonstrate higher concentrations than the infarct periphery.114 Concentrations of Lac during the evolution of an infarct also demonstrate temporal as well as spatial variability.121,286 Although the presence of Lac signiies ischemia, it does not necessarily signify actual irreversible infarction.19,32,116,286 A later and more speciic spectral change signifying actual cerebral infarction is reduced NAA concentration.286 Several studies have demonstrated both a reduction in NAA and appearance of Lac in human stroke.19,123,304,360 The reduced NAA level is thought to be related to actual neuronal damage (neuronal cell death or replacement by non–NAA-containing cells such as glial cells, which occurs in a delayed

fashion relative to the changes seen in Lac levels) and is correlated highly with poor clinical outcome.242,244,248,286 Pereira and coworkers used proton MRS and T2-weighted structural MRI to study a series of 31 patients with new middle cerebral artery distribution infarcts within the irst 72 hours following clinical onset of stroke symptoms. The authors noted that the combination of infarct volume and NAA concentration could accurately predict clinical outcome.266 In the acute stage, decreases in NAA levels can often be identiied in initial MR spectra. An animal model demonstrated NAA reduction within 30 to 60 minutes following induction of cerebral infarction.138,262,286 Regional variability in NAA concentrations is noted, just as with Lac, and the areas demonstrating the greatest elevation of Lac within an infarct also demonstrate the most marked NAA depression.19,105,121,286 Changes in Cho and Cr concentrations during acute infarction are more variable than changes involving Lac and NAA. Many studies have reported decreases in Cr levels.42,105,108,114,122,304 Nevertheless, a few studies documented no consistent change in Cr levels,108,114,121,258 and two studies have even noted increased levels of Cr.19,120 Variability in Cho levels has been equally problematic. Elevated Cho levels have been reported in acute infarction, and this elevation may be related to ischemic demyelination.19,120,286 However, this inding is not consistent; several studies have noted decreased42,121 or unchanged108,114,304 Cho levels. In the subacute stage, Lac levels decrease progressively from those present in the acute stage, with an approximately 36% reduction in Lac levels noted per week.122 Lac may disappear or persist at low levels in the chronic stage; it may also disappear in the subacute stage and recur in the chronic stage.19,115,121,122,144,302 Reasons for the persistence of Lac signals into the subacute and chronic phases are not entirely clear.286 In the chronic stage, NAA, Cr, and Cho levels decrease.286,304 Speciically the NAA level decreases in an irreversible fashion at an average rate of approximately 29% per week.19,105,114,122,144 The rate of decrease of Cr and Cho is less than that of NAA, although these levels also decrease in the subacute and chronic phases.97,105,114,286 The smaller relative decrease of Cho and Cr is probably related to both the relatively decreased vulnerability of glial cells to ischemia compared to neurons, and the reactive gliosis that occurs as a result of ischemic brain injury.122,286

Hypoxic-Ischemic Injury/Encephalopathy MRS has been used to evaluate brain damage due to perinatal asphyxia, or hypoxic-ischemic injury (HIE).4,28,124,128 HIE is the main cause of developmental injury leading to cerebral palsy. Standard images in neonates (cranial sonography, CT, and conventional MRI) obtained in the irst few days after injury may appear near normal. Proton MRS and DWI can detect brain injury on the irst day of life. However, to reveal the overall pattern and extent of HIE, DWI should be performed 2 to 4 days after insult.27,222 MRS can detect acute brain injury even in cases with negative conventional MRI and DWI.257 However, similar to DWI, the pattern of MRS evolves with time after the injury. Both diffusivity and metabolite ratios were reported to be abnormal on the irst or second day of life.27,222 The detected abnormal indings continued to worsen in most patients until the fourth or ifth day, after which the diffusivity and metabolite ratios started to normalize.27 In many cases the most severe damage (selective neuronal necrosis) involves the occipital gray matter and is manifested as a reduction in NAA and Cr levels and a proportional increase in Cho levels.4 This suggests that signiicant astrocyte survival may be present in these cases of necrosis secondary to HIE.4 In particularly severe cases, a Lac

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signal may also be present, with the Lac signal appearing during the irst 24 hours and persisting for at least 48 hours.265 This inding often precedes the reduction in the NAA/Cr ratio and the increase in the Cho/Cr ratio, both of which have been noted on MRS studies performed 1 to 2 weeks after the initial insult.309 The severity of the MRS changes appears to correlate with the severity of the initial insult and clinical outcome; persistent NAA and Cho signal abnormalities and the presence of Lac are associated with poor prognosis.26,128,141,315 Speciically, the presence of Lac in the acute phase has been associated with poor neurocognitive status at 1 year of age.26 Barkovich and coauthors have demonstrated that Lac/Cho ratios in the basal nuclei had particularly highly statistically signiicant associations with clinical outcome.26 The distribution of Lac elevation in the brain also correlates well with the severity of the injury; in severe asphyxia, the basal ganglia demonstrate greater Lac elevation than the arterial watershed regions; in mild to moderate asphyxia, the watershed regions demonstrate greater Lac elevation.25 Penrice and colleagues have shown that Lac/ NAA ratios in the thalami in particular correlate highly with degree of severity of asphyxia; the ratios in normal infants were less than 0.3, the ratios in infants with asphyxia were greater than 0.4, and the ratios in severely affected infants were greater than 0.5.25,264 Pu and others have shown that cases of moderate to severe HIE display detectable brain Glu/Gln (Glx) peaks on proton MR spectra.280 Elevated Glx/(Cr + PCr) ratios in these cases correlated positively with the Sarnat stage of HIE on both initial and follow-up MRS studies.280

Cerebral Infections Most applications of proton MRS in evaluating intracranial infections have involved the study of acquired immunodeiciency syndrome (AIDS) and AIDS-related conditions. Nevertheless, evaluation of cerebral abscesses with MRS has also been documented. Cerebral abscesses can be differentiated from necrotic brain neoplasms by MRS. Grand and coworkers, in their series of 34 cystic intracranial lesions, showed that at a TE of 136 milliseconds, detection of an amino acid resonance at 0.9 ppm in bacterial abscesses allows differentiation from necrotic neoplasms, which do not demonstrate this spectral signal.125 MR spectra of brain abscesses demonstrate absent or low Cho and Cr levels and a relatively decreased level of NAA, as well as the possible presence of substantial amounts of Lac.53,285 MR spectra of abscesses may show other signals at 0.97, 1.24, 1.36, 1.50, 1.89, 2.02, and 2.14 ppm, and the exact signiicance of these additional signals is not known.53 Mishra and colleagues have reported results from their study of 52 patients with cystic intraparenchymal ringenhancing lesions with surrounding edema, in which they compared the relative sensitivity of DWI (with ADC mapping) and proton MRS.233 Their chosen criteria for abscess diagnosis were ADC values less than 0.9 ± 1.3 × 10-3 mm2/sec and presence of Lac cytosolic amino acids either with or without presence of succinate, acetate, alanine, or glycine signals on MRS.194 Using these criteria, they found sensitivity for differentiation of abscess from nonabscess to be 0.72 for DWI/ADC and 0.96 for MRS.233 Lac and amino acid signals with or without other metabolites were observed in 25 of 29 cases of abscesses.233 In three patients with neurocysticercosis in their cohort, nonspeciic amino acid signals (n = 2), Lac (n = 3), acetate (n =1), succinate (n = 3), Cho (n = 2), and alanine (n = 3) were seen.233 Whereas diffusion restriction was suggestive of brain abscess, in the absence of diffusion restriction, proton MRS was necessary to accurately distinguish brain abscesses from cystic tumors.233 Various studies have shown resonances from acetate, succinate, and some amino acids (signals not seen in brain neoplasms) in addition to

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Lac, Ala, and lipid signals (which may also be seen with certain brain tumors).56 Similar indings have been reported by Castillo’s group and others in cases of toxoplasmosis and cysticercosis.53,56 The few reports in the literature regarding MR spectra of other infectious processes include studies of intracranial tuberculomas, Creutzfeldt-Jakob disease, and herpes simplex encephalitis.56 Prominent lipid resonances have been noted in intracranial tuberculomas, with particularly important signals at 1.3 and 0.9 ppm corresponding to the methylene and terminal methyl groups of fatty acids, respectively.56 Abnormally decreased NAA levels in both white and gray matter, as well as abnormally increased levels of MI in the white matter, have been noted in Creutzfeldt-Jakob disease, whereas reductions in NAA/Cho and NAA/Cr ratios and the presence of Lac signals have been noted in herpes encephalitis.56

Acquired Immunodeiciency Syndrome Various studies of applications of MRS to the evaluation of metabolic disturbances related to human immunodeiciency virus (HIV) infection have been recently performed; these studies have demonstrated reduced NAA concentrations in HIV-positive patients,63-65,67,160,231,301,329,342 including those who are asymptomatic227 or who display normal structural MRI indings.342 Increases in Cho and progressive decreases in NAA levels have been noted with disease progression.63-65,67,160,231,301,329,342 Increased levels of Gln/Glu (Glx) and MI have been noted in the late stages of HIV dementia.64 One study reported a decrease of both NAA and Cr along with increases in Cho and MI, both in structural brain lesions and normal-appearing areas of brain (on conventional MRI) in patients with AIDS.36,225 It is not clear whether the metabolic abnormalities in AIDS are due directly to the virus or represent secondary effects related to opportunistic infection or AIDS-related neoplasms.36 Nevertheless it appears that MRS may be able to detect subclinical metabolic abnormalities prior to clinical and brain structural manifestations of the disease.295 The diffuse cortical atrophic changes and white matter hyperintensities noted on T2-weighted images are late indings in the AIDS dementia complex. MRS may be particularly useful in the evaluation of infants of HIVinfected mothers; it may be able to demonstrate abnormalities in the infant brain as early as 10 days after birth, whereas seroconversion is dificult to determine during the irst 6 months and conventional brain MRIs may be normal up to about 1 year of age.53,78,206 Toxoplasmosis, lymphoma, cryptococcal infection, and progressive multifocal leukoencephalopathy (PML) are all frequently seen in HIV-positive patients and may be dificult to distinguish based on structural MRI alone.204 The distinction among these conditions is critical for determination of optimal therapy, because major differences in treatment approaches exist among these conditions.204 MRS can allow differentiation because each entity presents with a relatively unique metabolic signature.66,204 Toxoplasmosis demonstrates decreased MI, Cho, Cr, and NAA, with a 15- to 20-fold increase in Lac/lipids.66,204 CNS lymphomas demonstrate increased Cho, Lac, and lipids (similar magnitude) as well as decreased NAA and MI.66,204 PML tends to demonstrate increased MI and Cho and decreased NAA and Cr.66,204 Cryptococcal infection is associated with decreased MI, Cho, Cr, NAA, and increased lipids but not Lac.66,204 MRS may also prove to be a useful means of monitoring both disease progression and treatment effects in patients with AIDS.65,248,301 Speciically it has been suggested that monitoring of the eficacy of antiretroviral therapy—and even prediction of a patient’s response to therapy—may be performed with MRS.295,365

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Multiple Sclerosis Multiple sclerosis (MS) is a disease that is manifested primarily as multifocal demyelination, although signiicant axonal injury and wallerian degeneration are usually present as well.11,71,155,215,248,295 In MS, the axonal loss rather than the demyelination may be responsible for the neurologic impairment seen in these patients.214,295 Active demyelinating plaques generally demonstrate enhancement on MR scans following Gd administration, in addition to displaying hyperintensity on T2-weighted and FLAIR conventional MR sequences.53 Conventional MRI is the most sensitive imaging method to diagnose MS; however, MRI’s ability to detect lesion heterogeneity and involvement of surrounding brain tissue is limited. Proton MRS can evaluate the degree of metabolic impairment in lesions, normalappearing white matter on conventional MRI, and gray matter.90 Substantial reductions in NAA concentration are noted in acute (active) MS lesions, and these reductions correlate highly with clinical neurologic impairment. Partial recovery of NAA levels is not uncommon, and these changes are also relected in clinical improvement; whether the partial recovery of NAA levels is due to reduction of edema or to actual recovery of neuronal function is not clear.48,295 In the acute phase, marked increases in Cho concentration, moderate increases in Lac, and increases in mobile lipid signals and “marker signals” in the range of 2.0 to 2.6 ppm may be present.11,36,129 The increase in Cho levels is due to release of phosphocholine and glycerophosphocholine during active demyelination.36 The mobile lipid signals are products of myelin breakdown, and the marker signals are of uncertain etiology but appear to be typical of demyelinating conditions in general.36,53 It has been suggested that lipid concentration increases may precede signal hyperintensity development on T2-weighted conventional MR sequences.246,295 The presence of Lac may be related to local inlammatory iniltrates associated with the demyelinating plaques and their effects on local cerebral vasculature.11,295 A transient but signiicant decrease in Cr levels in the hyperacute stage may revert to normal in the subacute and chronic stages.295 Increases in MI concentrations may be seen on short TE spectra; MI is usually detected when the demyelinating process is severe.36,88,295 Elevated Glu levels reported recently in acute MS lesions (and normal-appearing white matter but not chronic lesions) suggest an association between axonal injury and impaired metabolism of Glu.322 Long TE proton MR spectra from acute MS lesions showing decreased NAA and elevated Cho and Lac levels may resemble spectra of brain tumors.299 However, elevated Glu/Gln levels in short TE MR spectra in tumefactive demyelinating lesions may help differentiate demyelination from neoplasms, which do not typically show elevated Glu/Gln signals.69,322 Reduction of NAA/Cr ratios has been noted not only in structural lesions (visible demyelinating plaques) but even in white matter, which appears normal by conventional T2-weighted MRI; thus, these MRS indings suggest that conventional MR sequences may underestimate the true extent of brain tissue involvement by MS.36,87,110,292 Although much of the reduction has been attributed to decreases in absolute concentrations of NAA, controversy exists regarding possible increases in Cr levels as well.87,248,289 The metabolite changes noted in MRS may be better correlated with actual clinical status than the number or volume of hyperintense structural brain lesions on conventional T2-weighted sequences.10,341 The reduction in NAA in normalappearing white matter correlates best with the degree of clinical disability.295 Gonen and colleagues118 have suggested that measurement of whole-brain NAA concentration may serve as an effective and

reproducible measure of disease load in MS and may be used to measure disease progression. In the chronic phase of MS, axonal loss and mild cortical atrophy may occur. Although acute plaques demonstrate edema and demyelination, chronic plaques demonstrate gliosis and mild associated neuronal loss.36 Incomplete recovery of axonal damage leads to irreversible clinical disabilities. NAA levels are decreased both in the structural lesions identiied on conventional MR sequences and in surrounding normalappearing white matter in the chronic phase, and this NAA decrease corresponds to the axonal and mild neuronal loss.295 Normal NAA levels in the acute phase of MS may suggest that the axons in these cerebral regions have not yet sustained permanent damage, whereas in the chronic phase, when axonal loss has occurred, NAA levels are decreased.53 Free mobile lipids and marker signals may also be seen in MR spectra in the chronic phase in MS.53 Because MRS provides valuable insight into the various stages of the evolution of MS plaques and the physiologic and metabolic changes associated with this evolution, in the near future it may also provide a reliable means of effectively monitoring responses to new therapeutic interventions.104 A recent study has already explored serial spectroscopic changes in active MS plaques during pharmacologic intervention.209 These interventions may be designed to target particular stages in the development and maturation of these plaques and thus may prevent progression of the disease.

OTHER APPLICATIONS OF PROTON MRS IN THE CENTRAL NERVOUS SYSTEM Other CNS applications of proton MRS include the study of psychiatric diseases, upper motor neuron disease (e.g., amyotrophic lateral sclerosis [ALS]), Huntington’s disease, and parkinsonian syndromes, among other clinical entities). In patients with schizophrenia, the most consistent indings include decreased NAA levels in the temporal lobes.169 In bipolar affective disorder, elevated Cho, NAA, and MI levels in the basal ganglia and elevated levels of Glu in the parietal lobes have been described.49,308 Children with attention deicit hyperactivity disorder (ADHD) demonstrate abnormally elevated NAA/Cr, Glu/Cr, and Cho/Cr ratios in the frontal lobes when compared with age-matched controls.49 In patients with ALS, the NAA/Cr ratio is signiicantly decreased in the motor and premotor cortices, and similar decreases are present in the brainstem.36,85 In Huntington’s disease, a reduced NAA/Cho ratio is present in both the basal ganglia and the cerebral cortex, and Lac elevations in these areas may also be present.162,295 MRS evaluation of the parkinsonian syndromes has revealed typical absence of metabolic abnormalities in the basal ganglia in idiopathic Parkinson’s disease, as opposed to reductions in the basal ganglia NAA/Cr and NAA/Cho ratios in other parkinsonian syndromes such as progressive supranuclear palsy and corticobasal degeneration.295 Another entity for which proton MRS has been clinically useful is hepatic encephalopathy (HE). Ross et al.293 used proton MRS to study 20 patients with cirrhosis and found that compared with control subjects, patients with liver disease and no HE showed a reduction in Cho/Cr without altered MI/Cr or Glx/Cr. Patients with subclinical HE had, in addition to lower Cho/Cr, a substantial reduction in MI/Cr and increases in the beta-, gamma-, and alpha-Glx regions of the spectrum.

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proton magnetic resonance spectroscopic imaging. Neurology 47:696–704, 1996. Tedeschi G, Bertolino A, Righini A, et al: Brain regional distribution pattern of metabolite signal intensities in young adults by proton magnetic resonance spectroscopic imaging. Neurology 45:1384–1391, 1995. Tedeschi G, Lundbom N, Raman R, et al: Increase of choline signal coincides with malignant degeneration of cerebral gliomas: A serial proton magnetic resonance spectroscopic imaging study. J Neurosurg 87:516–524, 1997. Tedeschi G, Schiffmann R, Barton NW, et al: Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse white matter hypomyelination. Neurology 45:1526–1532, 1995. Tien RD, Lai PH, Smith JS, et al: Single-voxel proton brain spectroscopy exam (PROBE/SV) in patients with primary brain tumors. AJR Am J Roentgenol 167:201–209, 1996. Tochon-Danguy HJ, Sachinidis JL, Chan F, et al: Imaging and quantitation of the hypoxic cell fraction in an animal model of intracerebral high grade glioma using [18F]luoromisonidazole (FMISO). Nucl Med Biol 29:191–197, 2002. Toft PB, Leth H, Lou HC, et al: Metabolite concentrations in the developing brain estimated with proton MR spectroscopy. J Magn Reson Imaging 4:674–680, 1994. Tourbah A, Stievenart JL, Gout O, et al: Localized proton magnetic resonance spectroscopy in relapsing remitting versus secondary progressive multiple sclerosis. Neurology 53:1091–1097, 1999. Tracey I, Lane J, Chang I, et al: 1H magnetic resonance spectroscopy reveals neuronal injury in a simian immune deiciency virus macaque model. J Acquir Immune Deic Syndr Hum Retrovirol 15:21–27, 1997. Tzika AA, Ball WS, Vigneron DB, et al: Childhood adrenoleukodystrophy: Assessment with proton MR spectroscopy. Radiology 189:467–480, 1993. Tzika AA, Vajapeyam S, Barnes PD: Multivoxel proton MR spectroscopy and hemodynamic MR imaging of childhood brain tumors: Preliminary observations. AJNR Am J Neuroradiol 18:203–218, 1997. Tzika AA, Vigneron DB, Dunn RS, et al: Intracranial tumors in children: Small single-voxel proton MR spectroscopy using short- and long-echo sequences. Neuroradiology 38:254–263, 1996. Urenjak J, Williams SR, Gadian DG, et al: Speciic expression of N-acetylaspartate in neurons, oligodendrocyte-type 2 astrocyte progenitors, and immature oligodendrocytes in vitro. J Neurochem 59:55–61, 1992. Vagnozzi R, Signoretti S, Cristofori L, et al: Assessment of metabolic brain damage and recovery following mild traumatic brain injury: A multicenter proton magnetic resonance spectroscopic study in concussed patients. Brain 133:3232–3242, 2010. van der Knaap MS, Barth P, Gabreels F, et al: A new leukoencephalopathy with vanishing white matter. Neurology 48:845– 855, 1997. van der Knaap MS, Ross B, Valk J: Uses of MR in inborn errors of metabolism. In Kucharczyk J, Mosely M, Barkovich AJ, editors: Magnetic resonance neuroimaging, Boca Raton, FL, 1994, CRC Press, pp 245–318. van der Knaap MS, van der Grond J, van Rijen PC, et al: Agedependent changes in localized proton and phosphorus MR spectroscopy of the brain. Radiology 176:509–515, 1990. van der Knaap MS, van der Grond J, Luyten PR, et al: H-1 and P-31 magnetic resonance spectroscopy of the brain in degenerative cerebral disorders. Ann Neurol 31:202–211, 1993. Videen JS, Michaelis T, Pinto P, et al: Human cerebral osmolytes during chronic hyponatremia: A proton magnetic resonance spectroscopy study. J Clin Invest 95:788–793, 1995. Vigneron DB, Barkovich AJ, Noworolski SM, et al: Three-dimensional proton MR spectroscopic imaging of premature and term neonates. AJNR Am J Neuroradiol 22:1424–1433, 2001. Vion-Dury J, Meyerhoff DJ, Cozzone PJ, et al: What might be the impact on neurology of the analysis of brain metabolism by in vivo magnetic resonance spectroscopy? J Neurol 241:354–371, 1994.

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355. Wang ZJ, Berry GT, Dreha SF, et al: In vivo proton brain MRS of galactosemia. Paper presented at the Sixth Annual Meeting of the International Society of Magnetic Resonance in Medicine, 1998, Sydney, Australia, p 538. 356. Wang ZJ, Berry GT, Dreha SF, et al: Proton magnetic resonance spectroscopy of brain metabolites in galactosemia. Ann Neurol 50:266–269, 2001. 357. Wang Z, Sutton LN, Cnaan A, et al: Proton MR spectroscopy of pediatric cerebellar tumors. AJNR Am J Neuroradiol 16:1821–1833, 1995. 358. Wang Z, Zimmerman RA, Sauter R: Proton MR spectroscopy of the brain: Clinically useful information obtained in assessing CNS diseases in children. AJR Am J Roentgenol 167:191–199, 1996. 359. Wang ZJ, Zimmerman RA: Proton MR spectroscopy of pediatric brain metabolic disorders. Neuroimaging Clin N Am 8:781–807, 1998. 360. Wardlaw JM, Marshall I, Wild J, et al: Studies of acute ischemic stroke with proton magnetic resonance spectroscopy: Relation between time from onset, neurological deicit, metabolite abnormalities in the infarct, blood low, and clinical outcome. Stroke 29:1618–1624, 1998. 361. Warren KE, Frank JA, Black JL, et al: Proton MRSI in children with recurrent brain tumors. J Clin Oncol 18:1020–1026, 2007. 362. Wells W, Pittman T, Wells H, et al: The isolation and identiication of galactitol from the brains of galactosemia patients. J Biol Chem 240:1002–1004, 1965. 363. Wheaton P, Mathias JL, Vink R: Impact of pharmacological treatments on cognitive and behavioral outcome in the postacute stages of adult traumatic brain injury: A meta-analysis. J Clin Psychopharmacol 31:745–757, 2011. 364. Whitmore GF, Varghese AJ: The biological properties of reduced nitroheterocyclics and possible biological mechanisms. Biochem Pharmacol 35(1):97–103, 1986.

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365. Wilkinson ID, Lunn S, Miszkiel KA, et al: Proton MRS and quantitative MRI assessment of the short term neurological response to antiretroviral therapy in AIDS. J Neurol Neurosurg Psychiatry 63:477–482, 1997. 366. Witt ST, Lovejoy DW, Pearlson GD, et al: Decreased prefrontal cortex activity in mild traumatic brain injury during performance of an auditory oddball task. Brain Imaging Behav 4:232–247, 2010. 367. Wittsack H, Kugel H, Roth B, et al: Quantitative measurements with localized 1H MR spectroscopy in children with Canavan’s disease. J Magn Reson Imaging 6:889–893, 1996. 368. Wright AJ, Fellows G, Byrnes TJ, et al: Pattern recognition of MRSI data shows region of glioma growth that agrees with DTI markers of brain tumor iniltration. Magn Reson Med 62:1646–1651, 2009. 369. Yaksh TL, Anderson RE: In vivo studies on intracellular pH, focal low and vessel diameter in the cat cerebral cortex: Effects of altered CO2 and electrical stimulation. J Cereb Blood Flow Metab 7:332–341, 1987. 370. Yu X, Liu Z, Yian Z, et al: Stereotactic biopsy for space occupying lesions: Clinical analysis of 550 cases. Stereotact Funct Neurosurg 75:103–108, 2000. 371. Zagzag D, Zhong H, Scalzitti JM, et al: Expression of hypoxia-inducible factor 1-alpha in brain tumors: association with angiogenesis, invasion and progression. Cancer 88:2606–2618, 2000. 372. Zeng Q-S, Li C-F, Zhang K, et al: Multivoxel 3D MR spectroscopy in the distinction of recurrent glioma from radiation injury. J Neurooncol 84:63–69, 2007. 373. Zhang K, Li C, Liu Y: Evaluation of invasiveness of astrocytoma using 1 H-magnetic resonance spectroscopy: correlation with expression of matrix metalloproteinase-2. Neuroradiology 49(11):913–919, 2007. 374. Zimmerman RA, Wang Z: Proton spectroscopy of the pediatric brain. Riv Neuroradiol 5(Suppl 1):5–8, 1992.

18 Meningeal Processes Melanie B. Fukui, Sheilah Curran-Melendez, and Carolyn Cidis Meltzer

ANATOMY AND EMBRYOLOGY Meninges The meninges, which form the coverings of the brain and spinal cord, develop from the meninx primitiva.71 The neural tube is surrounded by this dense cellular layer shortly after the neural tube closes.126 As early as 32 days and as late as 44 days of gestation, the meninx primitiva begins to cavitate to form the cerebral cisterns by gradually decreasing its cellular component and enlarging its intercellular space.126 The periphery of the meninx primitiva, however, develops more dense cellularity to become the primitive dura mater.126 The earliest subarachnoid space (SAS) is ventral to the brainstem. As this space expands, the prepontomedullary cisterns and anterior spinal SAS are formed.126,158 At approximately 41 days, the space is extended to create perimesencephalic and dorsal mesencephalic cisterns.125,126,158 The primitive meninx is composed of totipotential mesenchymal cells of neural crest origin.71 The remnants of incomplete differentiation of these pluripotential cells may be seen as deposits of fat, or lipomas, in and around the basal cisterns, corpus callosum, and cavernous sinuses.158 The order of regression of the primitive meninx is relected in the distribution of lipomas.158 Thus intracranial lipomas are thought most appropriately to represent developmental rather than neoplastic pathology of the meninges.158 This network of concentric membranes consists of the pachymeninx (dura mater) and the leptomeninges (arachnoid and pia mater) (Fig. 18-1). The dura mater is the most supericial membrane, a thick tough structure composed of dense connective tissue.24 The dura is composed of two layers: (1) an outer periosteal layer, which is highly vascularized, serves as the true periosteum of the inner table of the calvaria, and is not of meningeal origin,145 and (2) an inner meningeal layer, which is derived from the meninx. The cranial dural layers split to form the venous sinuses. The term dura (from Latin durus, meaning “hard”) is an apt descriptor of the structure that maintains the position of the cerebral hemispheres and posterior fossa structure by its relections, such as the falx cerebri and tentorium cerebelli. The arachnoid and pia mater constitute the leptomeninges (from Greek lepto and meninx, meaning “slender membrane”). The delicate arachnoid is adjacent to the inner surface of the dura and is thinner over the convexities than at the base of the brain. The pia mater is a ine membrane that extends into the depths of the sulci.

Extraaxial Spaces The meninges delimit the extraaxial compartments of the central nervous system (CNS). The epidural space is created when the dura is separated from the calvaria. Although the subdural space (between the

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dura and arachnoid membranes) has conventionally been characterized as a potential space containing minimal luid, cells of the arachnoid actually form an intimate network with those of the meningeal dural layer.49 Electron microscopy has provided evidence that cells belonging to the inner dural layer may be found on both sides of this space when collections form in the subdural space.49,67 The subdural space, therefore, is formed by cleavage through the inner layer of the dura rather than by a true separation of dura and arachnoid and as such probably exists only in pathologic states.67 The SAS (between the arachnoid and pia mater) contains cerebrospinal luid (CSF), which lows throughout the CNS and drains into the venous sinuses through the valves of the arachnoid granulations.145 The pia and the arachnoid are joined by ine connective tissue and cellular septa that traverse the SAS.21 Near the base of the brain, though, the pia and arachnoid widely separate to accommodate the basal cisterns. Perivascular, or Virchow-Robin, spaces were originally thought to be potential pathways connecting the CSF and deep brain structures by virtue of continuity with the SAS.44 More recent studies, however, have concluded that perivascular spaces are within the subpial space, separated from the SAS by pia mater4 (Fig. 18-2).

Extraaxial Collections Fluid collections in the epidural space assume a localized biconvex coniguration as a result of the strong force needed to detach the irmly adherent dura from the inner table of the calvaria. The outer dural layer is most tightly adherent at sutures; classic teaching therefore holds that epidural collections do not cross suture lines.63 Uncommon exceptions to this rule do occur, however. After administration of paramagnetic contrast medium, the dura adjacent to an epidural hematoma (EDH) has a curvilinear enhancing appearance. An inlammatory reaction with formation of granulation tissue on the outer surface of the dura may produce increased thickness and intensity of enhancement in the dura immediately subjacent to an EDH, as demonstrated in Figure 18-3.70 Greater tissue contrast and multiplanar imaging capability contribute to the superior sensitivity of magnetic resonance imaging (MRI) compared with computed tomography (CT) in detecting small subdural luid collections.87 MRI is especially useful in cases of subacute subdural hematoma (SDH), which may appear isodense to cortex on CT. Subdural hygromas result from leakage of CSF into the subdural space, probably after a tear in the arachnoid. MRI can distinguish SDH from subdural hygroma by improved detection of blood products, which are absent in a hygroma, but it cannot distinguish normal from infected subdural luid, because peripheral dural enhancement may be seen in both infected and noninfected subdural collections (Fig. 18-4). A diffusely enhancing infected subdural collection may mimic an en plaque meningioma.105

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Calvaria Dura Barrier cells Subarachnoid space Pia mater

Arachnoid

FIG 18-1 Schematic representation of the dura and leptomeninges. (From Meltzer CC, et al: MR imaging of the meninges: Part 1. Normal anatomic features and nonneoplastic disease. Radiology 201:297–308, 1996.)

Arachnoid Subarachnoid space

Arachnoid vessel Pia mater

FIG 18-3 Epidural abscess. Enhanced axial T1-weighted image shows a lentiform epidural collection of pus with dural enhancement (arrows) that could mimic an epidural hematoma.

Parenchymal vessel

VirchowRobin space

FIG 18-2 Diagram illustrating the anatomy of the perivascular (VirchowRobin) space with respect to the pia mater and subarachnoid space. (Modiied from Fukui MB, et al: MR imaging of the meninges: Part 2. Neoplastic disease. Radiology 201:605–612, 1996.)

MAGNETIC RESONANCE IMAGING MRI is substantially more sensitive than CT for visualizing both normal and abnormal meninges40,58,73,108,155,157 (Fig. 18-5). Beamhardening and other artifacts adjacent to the calvaria may be partly responsible for the diminished detection of meningeal enhancement with CT. Experimental evidence suggests that more intense enhancement results in areas of blood-brain barrier disruption with gadolinium (Gd)-DTPA–enhanced MRI than with CT performed after iodinated contrast.94,139 It has been suggested that MRI may be as sensitive as or even superior to CT in detecting subarachnoid hemorrhage (SAH) in the subacute and chronic phases and when a luid-attenuated inversion recovery (FLAIR) pulse sequence is used.119,121 Other evidence suggests that FLAIR sequences may result in false-negative interpretations in the setting of SAH.171

Normal Meninges on MRI The normal meninges may demonstrate short segments of thin, low signal intensity on standard spin echo sequences.46 Intravenous (IV) administration of Gd-DTPA results in enhancement of the normal cranial dura, which lacks a blood-brain barrier, in an interrupted pattern of short linear segments that is typically most prominent

parasagittally30,155 (Figs. 18-6 and 18-7). Field strength may inluence the conspicuity of “normal” meningeal enhancement as well as detection of pathologic enhancement. Earlier literature reported a distinct lack of enhancement of normal meningeal structures with relatively low-ield-strength MRI.23 The greater signal-to-noise levels achieved at relatively higher ield strengths potentiate increased detection of meningeal enhancement (see Fig. 18-6). Cohen and colleagues reported that meningeal enhancement present on more than three contiguous 1.5 tesla (T) spin echo MRI was highly correlated with signiicant intracranial abnormality.30 Thick, long, or intensely enhancing segments, as well as nodular meningeal enhancement, are particularly suspect. The normal falx and dura may occasionally enhance in a thin uniform pattern.88 The typical lack of normal meningeal enhancement observed in MRI of the spine may relect the absence of the vascular outer dural layer that is found in the cranial pachymeninx.

MRI for Detection of Meningeal Disease The optimal imaging protocol for detection of meningeal disease is based on (1) technique, (2) sensitivity, (3) role, (4) cardinal signs, and (5) principal patterns (Box 18-1).

Imaging Technique The selection of MRI has a signiicant impact on the conspicuity of normal meningeal enhancement and sensitivity in detecting meningeal disease (see Figs. 18-6 and 18-7). Numerous factors inluence the appearance of the meninges on MRI, including (1) the presence and amount of MR contrast agent administered, (2) the type of pulse sequence performed, and (3) the exact pulse sequence parameters. For partial saturation (spin echo or gradient echo), short echo time (TE) sequences, crucial imaging parameters include the repetition time (TR) and excitation lip angle. The shorter the TR, the greater the degree of saturation of magnetization (i.e., decreased signal intensity) from all imaged tissues. As a result, contrast-enhancing tissue will be more conspicuous against the more saturated (i.e., hypointense)

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A

B FIG 18-4 Subdural empyema. A and B, Enhanced axial CT images at the level of the falx cerebri show dural enhancement surrounding a subdural empyema.

A

B FIG 18-5 Superior sensitivity of MRI over CT in detection of meningeal disease: Pott’s puffy tumor. A, Enhanced axial CT image at the level of an extracranial subperiosteal collection of pus. B, Enhanced axial MRI obtained after administration of gadolinium at the same level shows enhancement of the subjacent dura-arachnoid (arrows). Detection of this meningeal enhancement prompted a change of antibiotics to improve CSF drug penetration.

background tissues on a typical short TR, large lip-angle gradient echo study than on a spin echo study. Therefore the normal meninges usually exhibit diffuse enhancement on such ultrashort TR, large lipangle gradient echo imaging sequences (see Fig. 18-7).46 Imaging plane also affects visualization of meningeal enhancement; the coronal plane is preferred to axial MRI data for evaluating meningeal enhancement over the cerebral convexity. Similarly, factors that either increase signal from the meninges or decrease signal from background tissues enhance the contrast-to-noise ratio (CNR) and therefore the conspicuity of the enhancing meninges. Double-dosing and triple-dosing of paramagnetic contrast agents have demonstrated improved detection of parenchymal lesions with MRI,72

and there is evidence to support a similar dose effect for enhanced MRI of meningeal disease.86,140 More recently, cases of leptomeningeal metastases that had been diagnosed by MRI and high-dose (0.3 mmol/ kg) gadolinium that were not visualized with standard dosing (0.1 mmol/kg) technique have been reported62,86 (Fig. 18-8). Also, the use of fat saturation or magnetization transfer options increases the CNR by decreasing the signal from the background tissues.41,140

Sensitivity of MRI In the past, nonenhanced spin echo MRI was insensitive in detecting meningeal disease.108 The advent of the FLAIR sequence has greatly improved the sensitivity of MRI performed in the absence of

CHAPTER 18

A

Meningeal Processes

B FIG 18-6 Effects of ield strength on conspicuity of normal meningeal enhancement. A, Axial T1-weighted image acquired at 0.5 T immediately after injection of 0.1 mmol/kg gadolinium. B, One day later in the same patient, axial T1-weighted image acquired at 1.5 T immediately after injection of the same dose of gadolinium shows more prominent enhancement of the falx (arrows) than in A. (From Meltzer CC, et al: MR imaging of the meninges: Part 1. Normal anatomic features and nonneoplastic disease. Radiology 201:297–308, 1996.)

A

B FIG 18-7 Effects of pulse sequence on conspicuity of normal meningeal enhancement. A, Axial T1-weighted spin echo image in a patient shows faint short-segment meningeal enhancement (arrow). B, Axial spoiled gradient recalled echo image in the same patient shows thin continuous enhancement in a dura-arachnoid pattern. (From Meltzer CC, et al: MR imaging of the meninges: Part 1. Normal anatomic features and nonneoplastic disease. Radiology 201:297–308, 1996.)

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B

A

FIG 18-8 Effect of contrast dose on meningeal enhancement. Axial T1-weighted images obtained after administration of 0.1 mmol/kg (A) and 0.2 mmol/kg (B) doses of gadolinium show increased enhancement in a pia–subarachnoid space pattern at the higher dose in this patient with carcinomatosis of the meninges from gastric carcinoma.

Protocol for Magnetic Resonance Imaging Performed at 1.5 Tesla BOX 18-1

• Axial FLAIR image • Axial T1-weighted image • Axial and coronal T1-weighted image after administration of a double or a triple dose of gadolinium with a fat-saturation pulse or magnetization transfer

result in false-negative diagnoses of meningeal or SAS disease in cases of infectious meningitis, carcinomatosis, and SAH.171 In this series a false-positive diagnosis of meningeal or SAS pathology was made in the presence of normal and hyperintense cortex, susceptibility artifact, prominent pial vessels, concatenated saturation pulse, or low artifact.171 Neoplastic or inlammatory processes involving the SAS are best evaluated with paramagnetic contrast agents for visualization of enhancement of the accompanying meningeal involvement (Fig. 18-9).

FLAIR, luid-attenuated inversion recovery.

Role of Imaging

gadolinium to detect meningeal and SAS abnormalities.148,171 Singer and coworkers evaluated the use of FLAIR MRI in 62 patients (21 with proven SAS or meningeal disease) and 41 control patients.148 The sensitivity, speciicity, and accuracy of FLAIR for SAS disease were 85%, 93%, and 90%, respectively.148 Although all six cases of acute SAH were interpreted as abnormal on FLAIR images in the Singer series, this was a source of false-negative interpretation in the series by Williams and associates.148,171 Poor detection of SAH has been attributed to the relatively high oxygen tension in the SAS, which does not permit evolution to deoxyhemoglobin,65 and to the diluting effect of CSF. In 24 patients who underwent both FLAIR and Gd-enhanced T1-weighted MRI, FLAIR imaging (sensitivity, speciicity, and accuracy of 86%, 91%, and 89%, respectively) was superior to Gd-enhanced T1-weighted imaging (43%, 88%, and 74%).148 Williams and coauthors prospectively evaluated 376 consecutive cases performed with FLAIR imaging and showed that FLAIR may

Before and after gadolinium administration, MRI plays an important role in the diagnosis of meningeal neoplasm in the asymptomatic patient when CSF cytologic examination results are equivocal or when lumbar puncture is contraindicated.26,50,55,155 Imaging, however, does not replace CSF examination in diagnosis of meningeal neoplasm. The limited sensitivity of CSF cytologic examination continues to be a signiicant obstacle and reinforces the complementary role of imaging.56 The percentage of positive spinal CSF cytology in cases of primary CNS tumors with histologically conirmed meningeal involvement varies from 12% to 63% and is increased in symptomatic patients.8,59,91,115 With meningeal metastases from non-CNS neoplasms, CSF cytology was positive in 45% to 80% of cases, with higher yields after multiple spinal taps.122,165 CSF low cytometry increases the detection of CSF spread of hematologic malignancies over cytologic examination alone.22 The modest sensitivity of CSF cytology has fueled the search for CSF tumor markers to detect dissemination of neoplasm. Recent literature suggests that markers such as CA 15-3 may have value in detecting breast carcinoma in CSF, and nuclear magnetic spectroscopy may have value in detecting metabolites in CSF indicating disseminated lung adenocarcinoma.6,99 Additional tumor markers that

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541

B FIG 18-9 Axial FLAIR image in a patient with leptomeningeal spread of breast carcinoma (A) shows signal abnormality in a pia–subarachnoid space pattern (arrowheads) that enhances on the T1-weighted image after administration of gadolinium (B).

may be detected in CSF to indicate leptomeningeal neoplasm include transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA).161 Like CSF cytology, tumor detection with CSF markers may also be hampered by suboptimal sensitivity and speciicity.117,160 The sensitivity of MRI in detecting meningeal neoplasm was originally reported to be lower than that of CSF cytology, with high falsenegative rates: 30% to 33% for MRI and 58% for CT.27,177 The early studies, however, may have unwittingly introduced a selection bias by using positive cytology as an inclusion criterion.27,177 Later series comparing CT myelography with MRI and cytology showed a higher detection rate of CSF metastases with MRI (range, 65%-72%) than with CT myelography (range, 45%-47%) and cytology (29%).73,93 A Memorial Sloan-Kettering Cancer Center study showed that when the patient cohort was not restricted to patients with positive cytologic indings, the rate of detection of meningeal carcinomatosis was increased.50 This study examined 137 patients with signs and symptoms of meningeal disease.50 CT and MRI were assessed for signs of meningeal or SAS neoplasm, including hydrocephalus, enhancement of the dura, leptomeninges, and cranial nerves.50 Leptomeningeal metastases were identiied in 77 of 137 patients.50 The diagnosis of leptomeningeal metastases was based on the clinical and imaging indings alone in 31% of those cases.50 Abnormal imaging indings were reported much more frequently in cases of solid tumor primaries (90%) than in hematologic neoplasms (55%).50 More recent studies conirm these indings.178 A caveat in using MRI for the diagnosis of leptomeningeal tumor involvement, therefore, is that MRI is less sensi-

tive in detecting involvement of the meninges resulting from hematologic malignancies than in detecting detecting solid tumors.27,50,177,178 When the distinction between meningeal neoplasm and inlammatory meningeal disease cannot be established by CSF and clinical data, MRI can support the diagnosis of neoplasm and guide meningeal biopsy.84,98 Although infectious meningitides are often uncovered by CSF analysis, MRI may be used to target meningeal biopsies when needed. Cheng and coworkers reported an improved yield from meningeal biopsy specimens in cases of chronic meningitis when tissue specimens were obtained from enhancing regions identiied on MRI study29 (Fig. 18-10). MRI has an advantage over CSF examination in its ability to characterize bulky neoplastic disease that may be more responsive to radiation therapy.26 Because CSF cytologic examination produces a higher false-negative rate in focal than in diffuse disease,15,56 imaging may be of particular value in detecting focal spread of neoplasm to the meninges or SAS. MRI also has the potential to allow noninvasive monitoring of treatment response, although it is conceivable that the imaging abnormalities may persist beyond the eradication of neoplastic cells in the CSF.173 In a series of patients with coccidioidal meningitis, diminution of meningeal enhancement was seen in treated patients with improving CSF proiles.175 Therefore MRI also may be useful as a means of monitoring response to therapy in fungal meningeal disease.175 Imaging is a useful adjunct for the diagnosis of neoplastic meningeal disease in the appropriate clinical setting, along with CSF examination to exclude infectious or noninfectious processes of the meninges.50

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A

B

C FIG 18-10 Chronic meningitis. A, Thick slightly irregular dura-arachnoid enhancement on axial T1-weighted imaging proved to be idiopathic hypertrophic pachymeningitis on biopsy. B and C, In another patient, thin slightly irregular dura-arachnoid enhancement on axial (B) and coronal (C) T1-weighted imaging also proved to be idiopathic hypertrophic pachymeningitis on biopsy.

Finally, imaging may allow the clinician to assess outcome, in that diffuse leptomeningeal involvement confers a poor prognosis.16

Cardinal Imaging Signs of Meningeal Pathology The main imaging indings that have been associated with meningeal pathology are as follows33,43,50,82,93,136,154,155,177: • Hydrocephalus (Fig. 18-11) • Dura and arachnoid enhancement or signal abnormality (see Fig. 18-10)

• Pia and SAS enhancement or signal abnormality (see Fig. 18-11) • Subependymal enhancement or signal abnormality (Fig. 18-12) Hydrocephalus may or may not be associated with enhancement of the meninges or ependyma. In this setting, hydrocephalus alone implies a resorptive block to CSF low. Hydrocephalus may occur in the setting of SAH, infectious or noninfectious meningitis, and neoplasm. In the patient with neoplastic meningeal disease, hydrocephalus is more likely when leptomeningeal invasion or SAS has occurred rather than when neoplasm is limited to the dura.166

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B

A

FIG 18-11 Hydrocephalus with ependymal enhancement and pia–subarachnoid space abnormality. A, Axial T1-weighted image obtained after gadolinium administration shows enlargement of the lateral ventricles and thin linear ependymal enhancement. B, There is a pia-subarachnoid enhancement pattern between the cerebellar folia and along the third cranial nerves, indicating meningeal spread of small cell lung carcinoma in a patient with multiple cranial neuropathies.

A

B FIG 18-12 Focal nodular ependymal enhancement. A, Nodular enhancement of the ependyma of the frontal horns was the probable entry point for subarachnoid spread of melanoma. B, Sagittal T1-weighted image of the lumbar spine shows nodular enhancing drop metastases to the cauda equina (arrowheads).

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A

B FIG 18-13 Diffuse nodular pia–subarachnoid space enhancement. A and B, Multiple pial-based enhancing nodules are present in this patient with disseminated lung carcinoma.

Enhancement of the meninges may occur in the spine or brain. Meningeal or subependymal enhancement may be focal (Fig. 18-13) or diffuse (see Fig. 18-12) and may have either a smooth or nodular contour (Fig. 18-14; see Fig. 18-13). Diffuse leptomeningeal involvement is a harbinger of a worse prognosis than focal disease.16 Although a nodular pattern of enhancement may suggest neoplasm, it is not speciic; nonneoplastic entities (e.g., sarcoidosis) may also produce nodular thickening of the meninges (see Fig. 18-14A and B). Iniltration of the leptomeninges overlying the convexities or in the basal cisterns may result in sulcal or cisternal obliteration on a noncontrast T1-weighted image (Fig. 18-15) or a FLAIR sequence (see Fig. 18-9). Minimal shortening of T1 and T2 relaxation times in the cisternal CSF (“dirty CSF sign”) may be seen on nonenhanced MRI (see Fig. 18-15).18 In rare instances, subarachnoid tumor or inlammatory exudates may result in distention of the SAS or perivascular (subpial) spaces (Fig. 18-16).

Imaging Patterns Two distinct patterns of meningeal enhancement or signal abnormality may be observed with MRI. The dura-arachnoid pattern follows the inner contour of the calvaria (Fig. 18-17), whereas the pia mater–SAS pattern extends into the depths of the sulci (Fig. 18-18). Enhancement or signal abnormality surrounding the brainstem is always of the pia mater–SAS type, in that the arachnoid is clearly separated from the pia mater by the intervening basal cisterns in this region. Although pia mater–SAS enhancement does occur more commonly in the setting of meningitis than with tumor involvement, both inlammatory and neoplastic processes may demonstrate either pattern.89,132 A diffuse appearance favors an inlammatory etiologic mechanism, whereas nodular meningeal enhancement suggests a neoplasm (Boxes 18-2 to 18-6). Dura-arachnoid pattern. Because the dura and arachnoid are closely approximated, the distribution of meningeal enhancement does not reliably distinguish purely pachymeningeal (dural) from leptomeningeal (arachnoidal and pial) involvement. As a result the dura-arachnoid pattern of enhancement does not imply that the leptomeninges or the SAS is spared. This fact has practical importance because some authors report a lower incidence of positive CSF

cytologic indings with the dural pattern, in contrast to the pial pattern, implying a lack of SAS neoplasm.127 A surprisingly moderate rate (55%) of positive CSF cytologic results was reported in a subset of 11 patients with a dura-arachnoid enhancement pattern on MRI.50 The presence of malignant cells in the CSF of patients in this subgroup implies neoplastic involvement of the arachnoid and SAS. This conirms the limitation of MRI in distinguishing abnormal enhancement of the dura from that of the arachnoid.50 When restricted to the dura, however, meningeal carcinomatosis often results in negative CSF cytology; in this setting, MRI can play an important role in disease detection. The dural tail sign, once considered speciic for meningioma, may be observed in a wide variety of other extraaxial lesions, including schwannoma (Fig. 18-19), dural metastases (Fig. 18-20), lymphoma, tuberculoma, and sarcoidosis.109 Occasionally a dural tail may be seen in association with intraaxial mass lesions such as gliomas or non-CNS metastases.109 Although this imaging feature has been useful in suggesting the diagnosis of meningioma, its lack of speciicity may occasionally cause misleading interpretation of MRI.109 Similar signal, shape, and enhancement characteristics found with several of these lesions may further confound the distinction between meningiomas and other entities.109 Pia mater–subarachnoid space pattern. Similarly, the pia mater–SAS pattern of enhancement may relect neoplasm within the SAS, tumor iniltration of the pia mater, or both.177 The pia mater–SAS pattern is more common in patients with infectious meningitis than in those with a neoplasm,89,132 although the pia mater–SAS distribution is not at all speciic for inlammation. A higher rate of positive CSF cytologic indings has been reported in conjunction with the pia mater–SAS pattern than with the duraarachnoid pattern of enhancement in cases of neoplasm.127 This may relect the anatomy of the blood-brain barrier with respect to the meninges.89 The dura lacks a blood-brain barrier because its capillary endothelium has a discontinuous cell layer, whereas the outer layer of the arachnoid has capillaries with a continuous cell layer and tight junctions.142,143 Bloodborne neoplastic cells, therefore, may gain access to the dura more easily than to the SAS.89 A pia mater–SAS pattern

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C FIG 18-14 Nonneoplastic focal nodular and linear meningeal enhancement. A and B, Nodular enhancement in a pia-subarachnoid pattern (arrows) mimics neoplasm in a case of sarcoidosis. C, Focal linear enhancement in a linear dura-arachnoid pattern (arrows) in a different case of sarcoidosis.

BOX 18-2

Differential Diagnosis: Focal Dura-Arachnoid Pattern

BOX 18-3

Infectious Adjacent petrous apicitis/sinusitis/mastoiditis Adjacent abscess or cerebritis Fungal infection (Aspergillus)

Infectious Bacterial (unusual)

Noninfectious Inlammatory Reactive Calvarial metastasis Subdural or epidural hematoma Acute infarction Iatrogenic: catheter or craniotomy Sarcoidosis Neoplastic Meningioma Breast carcinoma Prostate carcinoma Lymphoma Posttransplant lymphoproliferative disorder (PTLD)

Differential Diagnosis: Diffuse Dura-Arachnoid Pattern

Noninfectious Inlammatory Reactive Diffuse calvarial metastases Extensive subdural hematoma Iatrogenic: response to catheter or craniotomy Low intracranial pressure states Cerebrospinal luid leak After lumbar puncture (unusual) Spontaneous intracranial hypotension (rare) Hypertrophic cranial pachymeningitis (rare) Wegener’s granulomatosis (rare) Multiple sclerosis (rare) Neoplastic Breast carcinoma Prostate carcinoma

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C FIG 18-15 “Dirty CSF sign” and ventricular debris. T1-weighted image (A) demonstrating obliteration of bilateral sulci, and FLAIR image (B) showing material that is hyperintense to CSF within the subarachnoid space (arrows) in a patient with gram-positive meningitis. C, After gadolinium administration there is extensive pia–subarachnoid space enhancement.

may relect SAS enhancement, pial enhancement, or both.48 Gadolinium may leak through capillary tight junctions that have been disrupted by neoplastic invasion of the meninges48 and directly enter the CSF.

NONNEOPLASTIC MENINGEAL DISEASE Infectious Meningitis Bacterial Meningitis Bacterial meningitis results from hematogenous spread of infection or occasionally from direct extension from a paranasal sinus or mastoid

source.90 The mechanism of entry of bacteria from the intravascular space into the CSF is not well understood. Animal studies have suggested that bacterial cell wall elements provoke an inlammatory response that brings about opening of tight intercellular junctions in the arachnoidal capillary bed.89 This breakdown in the leptomeningeal blood-brain barrier allows bacteria to gain access to the SAS. Early congestion and hyperemia of the leptomeninges are succeeded by mixed inlammatory cell iniltration with exudate in the SAS, especially over the cerebral convexity (see Fig. 18-15). A link between meningeal enhancement and the degree of inlammatory cell iniltration of the leptomeninges has been proposed by

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B FIG 18-16 Perivascular space pattern. Axial T2-weighted image (A) and enhanced T1-weighted image (B) show distention of the perivascular spaces at the base of the brain by the gelatinous nonenhancing pseudocysts of cryptococcosis.

FIG 18-17 Diagram illustrating the dura-arachnoid pattern of meningeal abnormality that follows the inner table of the skull and the dural relections (arrows). (From Meltzer CC, et al: MR imaging of the meninges: Part 1. Normal anatomic features and nonneoplastic disease. Radiology 201:297–308, 1996.)

FIG 18-18 Diagram illustrating the pia–subarachnoid space pattern of meningeal abnormality that invaginates into sulci (arrows). (From Meltzer CC, et al: MR imaging of the meninges: Part 1. Normal anatomic features and nonneoplastic disease. Radiology 201:297–308, 1996.)

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BOX 18-4

Differential Diagnosis: Focal Pia Mater–Subarachnoid Space Pattern

BOX 18-6

Infectious Bacterial meningitis Tuberculous meningitis (basal) Fungal (Aspergillus, Cryptococcus, Coccidioides) Viral (herpes) Adjacent abscess or cerebritis Spirochetal (neurosyphilis)

Infectious Bacterial Spirochetal Neurosyphilis Lyme disease Viral (“aseptic”) meningitis CMV Varicella-zoster (spinal in AIDS)

Noninfectious Inlammatory Reactive Sarcoid Subarachnoid hemorrhage Multiple sclerosis (rare) Vascular Pial vascular malformation (e.g., Sturge-Weber syndrome) Subarachnoid hemorrhage Supericial siderosis Granulomatous angiitis Hamartomatous Meningioangiomatosis Neoplastic Primary CNS Glioblastoma multiforme Astrocytoma Primitive neuroectodermal tumor Medulloblastoma Germinoma Ependymoma Secondary neoplasm Melanoma Breast carcinoma Lung carcinoma False-positive on FLAIR image Normal, hyperintense cortex (especially at convexities) Susceptibility artifact Prominent pial vessels Flow artifact (especially in basal cisterns)

Differential Diagnosis: Diffuse Pia Mater–Subarachnoid Space Pattern

Noninfectious Inlammatory Reactive Irritative (“aseptic”) meningitis Response to foreign material: Contrast agents Chemical (e.g., ruptured dermoid) Subarachnoid hemorrhage Vascular Subarachnoid hemorrhage Neoplastic Primary CNS AIDS lymphoma Glioblastoma multiforme Astrocytoma Primitive neuroectodermal tumor Primary leptomeningeal gliomatosis (very rare) Secondary neoplasm Melanoma Breast carcinoma Lung carcinoma False-positive result on FLAIR image Concatenated saturation pulse AIDS, acquired immunodeiciency syndrome; CMV, cytomegalovirus; CNS, central nervous system; FLAIR, luid-attenuated inversion recovery.

CNS, central nervous system; FLAIR, luid-attenuated inversion recovery.

Differential Diagnosis: Perivascular Space Pattern BOX 18-5 Infectious Enhancing Tuberculosis Nonenhancing Cryptococcosis Neoplastic Carcinomatosis Breast carcinoma Lung carcinoma

FIG 18-19 Focal dura-arachnoid enhancement. A dural tail (arrowheads) adjacent to a left acoustic schwannoma illustrates the nonspeciicity of this sign as an indicator of meningioma on an enhanced axial T1-weighted image.

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FIG 18-20. Focal dura-arachnoid mass. CT scan (A, B) shows colon adenocarcinoma metastases to the calvaria (arrow) extending to the dura (arrows) on enhanced axial and coronal T1-weighted images (C, D).

Mathews and coworkers.108 The lack of gadolinium enhancement in some areas of minimal inlammation suggests a threshold effect whereby a critical degree of inlammatory reaction is required before meningeal enhancement may be observed.108 MRI is superior to CT in the evaluation of complications of meningitis, including subdural empyemas, dural venous thrombosis, secondary ischemia, and parenchymal lesions.28 Septic thrombosis of the superior sagittal sinus, although uncommon since the advent of antibiotics, may complicate bacterial meningitis150 (Fig. 18-21). When thrombosis is suspected, MRI is the imaging modality of choice for conirming the presence of thrombus. Absent low may be detected as lack of a normal low void in the sagittal sinus on short TR images and may be optimally demonstrated by magnetic resonance angiography (MRA) using two-dimensional phase-contrast tech-

niques.85 Conversely, localized meningeal enhancement may also be seen overlying an adjacent parenchymal infectious process, such as a brain abscess or encephalitis. Bacterial meningitis may result in ventriculitis, especially in the setting of gram-negative and iatrogenic infections.51 An early inding in ventriculitis may be that of irregular debris in the dependent portions of the ventricles.51 Infectious meningeal processes may occasionally spread across the pial barrier to cause cerebritis.

Mycobacterial Meningitis CNS tuberculosis is increasing in frequency, partly because of its proclivity to occur with human immunodeiciency virus (HIV) infection. Tuberculous meningitis commonly occurs as a result of disseminated pulmonary infection, usually along with parenchymal brain

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A

FIG 18-21 Diffuse dura-arachnoid enhancement. A, Coronal T1-weighted image shows dura-arachnoid enhancement (arrows) in a patient with meningitis and subsequent superior sagittal sinus thrombosis. B, There is an absence of low in the superior sagittal sinus on a sagittal phase-contrast MR venogram.

involvement, although it rarely may be seen as the sole manifestation of the disease.110 In contrast to bacterial meningitis, tuberculous infection is associated with a more insidious onset, fewer changes in the CSF proile, and higher rates of mortality and complications such as infarction. Although tuberculosis tends to involve the basal meninges, tuberculomas may occur within the brain parenchyma or subarachnoid, subdural, or epidural spaces18,133 (Fig. 18-22). In one series, meningeal enhancement was observed in 36% of HIV-infected patients with CNS tuberculosis evaluated with MRI.169 MRI of tuberculous meningitis demonstrates meningeal enhancement, most often in the basal cisterns, relecting the known predilection of tuberculosis for the base of the brain. Calciication of the basal meninges may also be seen and is more easily appreciated with CT than with MRI. Focal or diffuse dura-arachnoid enhancement may be observed on contrast-enhanced MRI scans of the spine in cases of suspected active tuberculous meningitis.95 Thickening, inlammation, and ibrosis of the leptomeninges are commonly seen at histopathologic examination. Meningitis may also be caused by a virus or fungus, a fact that is of particular importance in immunocompromised patients. In patients with acquired immunodeiciency syndrome (AIDS), a polyradiculomyelitis may develop in rare circumstances as a result of cytomegalovirus (CMV) or varicella-zoster virus infection.54 Diffuse enhancement of the cauda equina on MRI should alert the clinician to exclude these causes in AIDS patients.168

FIG 18-22 Multiple ring-enhancing tuberculomas are distributed throughout the perivascular spaces and basal pial surfaces on an axial T1-weighted image after administration of gadolinium.

Fungal Meningitis Fungal meningitis usually results from hematogenous dissemination of disease and is also often seen in immunosuppressed hosts. Fungal meningitides, such as those caused by Aspergillus, Cryptococcus, and Coccidioides species, may be demonstrated by contrast-enhanced MRI.107,113,175 Aspergillosis is an important cause of morbidity and mortality in organ transplant recipients and may be associated with focal, thick dura-arachnoid enhancement that resolves with treatment.113 Cryptococcus frequently infects patients with AIDS, but meningeal enhancement is seen only occasionally in cryptococcal meningitis, probably because of the blunted host response.108,144 Meningeal

enhancement was observed in only one in ive autopsy-proven cases of AIDS-related cryptococcosis studied with Gd-enhanced MRI.107 Cryptococcal infection tends to spread from the basal cisterns via perivascular spaces to the basal ganglia, brainstem, internal capsule, and thalamus.167 This produces a characteristic MRI appearance of nonenhancing dilated perivascular spaces, caused by infestation with the gelatinous pseudocysts of cryptococcal material (see Fig. 18-16). In contrast to the pattern seen with Cryptococcus, Wrobel and colleagues reported MRI enhancement of the meninges in 7 of 11 patients with coccidioidal meningitis.175 Enhancement was most prominent in

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FIG 18-23 Coccidioidomycosis. Axial T1-weighted image demonstrates diffuse meningeal enhancement within the suprasellar cistern in a patient with coccidioidomycosis diagnosed with lumbar puncture.

A

B

FIG 18-24 Lyme disease. Sagittal T1-weighted images of the lumbar

the basilar cisterns, the sylvian and interhemispheric issures (Fig. 18-23), and the upper cervical SAS. Spirochetal infections may exhibit both localized and diffuse meningeal enhancement.20 Similarly, smooth diffuse pia-SAS enhancement of the brainstem and the entire spinal cord has been reported in Lyme disease (Fig. 18-24), even in the absence of MRI evidence of parenchymal disease.36

Aseptic Meningitis Meningitis is designated “aseptic” when CSF cultures are sterile. Aseptic meningitis may have a variety of causes, including viral infection and irritation after introduction of foreign substances into the CSF (e.g., blood, chemical agents, contrast materials), or it may be seen against the backdrop of connective tissue disorders.110 MRI may demonstrate meningeal enhancement or subarachnoid signal abnormality (Fig. 18-25). In cases of suspected aseptic meningitis, performing MRI after administration of paramagnetic contrast medium may help prevent delays in diagnosis.45

Noninfectious Inlammatory Meningitis Noninfectious granulomatous disease can also involve the meninges. Approximately 5% of patients with sarcoidosis have neurologic manifestations; of those, the most common sign is that of cranial nerve palsies.153 Gd-enhanced MRI is the study of choice to document meningeal involvement and may show either the pia mater–SAS or the dura-arachnoid pattern (see Fig. 18-14).146,147,179 Striking thickening of the meninges may also be demonstrated. Sarcoid was present in 31% of 37 patients with chronic meningitis of unknown etiology examined with enhanced MRI and meningeal biopsy and as such was the most frequent cause of chronic meningitis in that series.29 Meningeal abnormality may also occur in Wegener’s granulomatosis135 (Fig. 18-26). Thickened nodular meninges on both enhanced CT and MRI in a patient with Wegener’s granulomatosis were reported by Tishler and colleagues.156 The imaging features relect the histopathologic indings of dural and brain biopsies that revealed granulomatous

spine before (A) and after (B) administration of intravenous gadolinium demonstrate thick linear enhancement of the spinal conus and all nerve roots of the cauda equina in a patient with Lyme disease.

iniltration of the dura and development of ibrosis and granulomas of the pia mater and arachnoid. Hypertrophic cranial pachymeningitis is a rare type of diffuse granulomatous inlammation that produces thickening, chronic inlammation, and ibrosis of the dura.104,106 Common presenting symptoms include headache, cranial nerve palsies, and ataxia. Diffuse dural enhancement (on enhanced T1-weighted images) or hypointense and thickened dura (on T2-weighted images) may be demonstrated on MRI (see Fig. 18-10). Diagnosis requires conirmation with dural biopsy. The disease may progress despite corticosteroid therapy. In rare instances, meningeal enhancement has been reported to accompany demyelinating disease. We are aware of few reports of meningeal enhancement on MRI in cases of multiple sclerosis (MS). One case displayed a diffuse dura-arachnoid pattern; another showed focal pial enhancement.11,35 Serial MRI of MS plaques suggests that parenchymal lesion enhancement is related to the inlammatory process associated with active demyelination.11 Analogously, meningeal enhancement in MS may result from extension of perivascular lymphoplasmacytic iniltration into the leptomeninges, found in 41% of autopsy cases.66 A similar inlammatory etiology was proposed by Fulbright and coauthors52 in describing enhancement of multiple cranial nerves in Guillain-Barré syndrome, a disorder characterized by peripheral demyelination (Fig. 18-27).

Iatrogenic Meningeal Enhancement Benign meningeal enhancement on MRI may result from mechanical disruption of the meninges from a variety of causes. Localized or diffuse dural enhancement may occur after craniotomy and may persist indeinitely23,40 (Fig. 18-28). It may be dificult to distinguish normal reactive postoperative enhancement from meningeal tumor involvement following craniotomy for tumor resection. Postoperative meningeal enhancement usually regresses over time, often resolving

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B FIG 18-25 Aseptic meningitis. Thin linear pia–subarachnoid space enhancement (arrowheads) is seen in a patient with headache and no organism growth on CSF culture on axial (A) and coronal (B) enhanced T1-weighted images.

A

B FIG 18-26 Wegener’s granulomatosis. A and B, Diffuse thickening and enhancement of the meninges in a dura-arachnoid pattern (arrows) are present in a patient with biopsy-proven Wegener’s granulomatosis on a contrast-enhanced CT scan.

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catheter may also result in diffuse or localized dural enhancement. In rare instances, dura-arachnoid enhancement may result from uncomplicated lumbar puncture.111 Dural enhancement after lumbar puncture occurs more commonly, however, when intracranial hypotension results, suggesting a CSF leak.17

Vascular Disease

FIG 18-27 Guillain-Barré syndrome. Sagittal T1-weighted image of the lumbar spine demonstrates thick linear enhancement of multiple nerve roots of the cauda equina in a patient with Guillain-Barré syndrome.

FIG 18-28 Postoperative meningeal enhancement. Coronal T1weighted image shows diffuse linear enhancement in a patient who had undergone previous craniotomy for meningioma.

Occasionally an acute cerebral infarction may demonstrate adjacent meningeal enhancement (Fig. 18-29). This “meningeal enhancement sign” occurs between day 2 and day 6 after infarction. It is seen with large supratentorial infarcts and usually has a dura-arachnoid coniguration.39,42 Although the cause of meningeal enhancement in cerebral infarction is not established, possible contributing factors include reactive hyperemia and local inlammation following meningeal irritation.39 Hemorrhage into the SAS also irritates the leptomeninges, causing inlammation of the pia mater and arachnoid.69 In severe cases, ibrosis may ensue and eventually may obliterate the SAS. Supericial siderosis is a rare condition resulting from deposition of hemosiderin in the leptomeninges and surface of the brain following recurrent SAH and is a cause of hearing loss.25,80,83 The leptomeninges are thickened and pigmented on pathologic examination. A characteristic hypointense rim is observed along the brain surface on T2-weighted images19,25 (Fig. 18-30). This hypointense border of hemosiderin deposits in supericial siderosis becomes exaggerated, and thus more readily detected, on gradient echo MRI as a result of augmented magnetic susceptibility effects.83 The thickened meninges may also enhance with gadolinium. Vasculitis rarely involves the meninges. Preferential involvement of small leptomeningeal vessels in granulomatous angiitis may result in meningeal enhancement.116 MRI is the modality of choice for evaluation of Sturge-Weber syndrome, a phakomatosis characterized by deranged vasculature of the face, brain, and meninges.149 Poor venous drainage and chronic ischemic damage to the underlying cortex develop as a result of the leptomeningeal vascular malformation that originates in the SAS. MRI of the brain shows supericial gyriform enhancement. This enhancement likely results from slow low within the leptomeningeal vascular malformation with or without enhancement of ischemia13,164 (Fig. 18-31). Meningioangiomatosis is a rare hamartomatous disorder of the leptomeninges distinguished by meningovascular proliferation and leptomeningeal calciication.3,68,130 A cortical mass with meningeal extension and heterogeneous signal intensity on T2-weighted images and demonstrating contrast enhancement on MRI has been reported130,170 (Fig. 18-32). Halper and coworkers have theorized that meningioangiomatosis is caused by a proliferation of both meningothelial cells and leptomeningeal vessels within perivascular spaces as they penetrate the cortex.68 A combined pia mater–SAS and dura-arachnoid pattern of enhancement has been rarely reported in association with migraine headaches.32,100 This unusual inding is attributed to hyperperfusion, documented on single-photon emission computed tomography (SPECT) or transcranial Doppler imaging.32,100

Toxic Meningeal Enhancement between 1 and 2 years after craniotomy.40 In addition, the distribution of enhancement may support a benign etiologic mechanism. In contrast to the typically basilar pattern of neoplastic meningitis, postoperative enhancement occurs more often over the convexities.23 The morphology of enhancement may also provide clues as to the cause. A nodular dural enhancement pattern or thick pia mater–SAS enhancement suggests recurrent tumor.79 Placement of a ventricular

Chemical meningitis may arise following rupture of dermoid or epidermoid cyst. This inlammation is likely provoked by the irritating effect of cholesterin crystals and keratin material discharged into the CSF.34,101 In such cases the diagnosis of ruptured dermoid is usually veriied by demonstration of droplets of high-signal lipid material dispersed throughout the SAS on nonenhanced T1-weighted MRI. Meningeal irritation resulting in contrast enhancement on MRI has also been reported in the setting of adverse drug reactions. Eustace and

C

A

FIG 18-29 Meningeal enhancement after infarction. A, Axial proton-density–weighted image shows the left frontal infarct. B, Sagittal T1-weighted image shows bright signal in the cortex of the left temporal infarct (arrows). C, There is gyriform enhancement on the axial T1-weighted image that is probably a combination of cortical and pial enhancement (arrows).

B

A

B FIG 18-30 Siderosis. The dark signal from hemosiderin outlines the pial surface of frontal and parietal lobes (A) and cerebellum (B) in this patient with supericial siderosis on axial T2*-weighted images.

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FIG 18-31 Sturge-Weber syndrome. A, Gyriform enhancement deines the pial vascular malformation and adjacent ischemic occipital cortex on an axial T1-weighted image. B, In another patient, axial CT image demonstrates gyriform calciication. C, Axial T2*-weighted image shows susceptibility artifact within left frontoparietal cortex and pia (arrow), consistent with calciication seen on CT. D, Coronal T1-weighted image shows gyriform enhancement due to pial vascular malformation.

Buff reported a case of ibuprofen-induced meningitis depicted by meningeal enhancement on MRI.45

Spontaneous Intracranial Hypotension Like the low-intracranial-pressure headache after complicated lumbar puncture, spontaneous intracranial hypotension is identiied by a postural headache that resolves after placement of an epidural blood patch.138 A CSF pressure of less than 60 mm H2O in the absence of previous lumbar puncture establishes the diagnosis. MRI has shown striking thick, diffuse dural-arachnoid enhancement.47,78 Subdural luid collections may occur in conjunction with this low-pressure state.138 An unsuspected spontaneous CSF leak may be the inciting factor (Fig. 18-33), and thus recognition of this combination of imaging and clinical indings should prompt a search

for the source of the leak. Identiication of this treatable cause of meningeal abnormality in association with the germane clinical features may prevent diagnostic delay and unnecessary meningeal biopsy.

NEOPLASTIC MENINGEAL DISEASE Primary Involvement Primary dural neoplasms are rare. Neoplasms arising from the dura are mesenchymal in origin because the dura is composed of ibrous tissue.141 Primary dural tumors bridge the entire range of benign (ibromas) to intermediate (ibromatosis) to malignant (sarcomas).137 An assortment of dural sarcomas has been reported, including chondrosarcoma, ibrosarcoma, and malignant ibrous histiocytoma.7,97,103

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B FIG 18-32 Meningioangiomatosis. A, Axial T2-weighted image reveals left temporal gyriform hypointensity with subcortical hyperintensity (arrows) that may represent the meningovascular proliferation. B, This axial spoiled gradient recalled acquisition in a steady state (GRASS) image does not reveal enhancement.

A

B FIG 18-33 Intracranial hypotension. A, Coronal T1-weighted image demonstrates diffuse dura-arachnoid enhancement in this patient who presented with severe headaches and whose CSF pressure was low on lumbar puncture. B, The axial T2-weighted image shows luid presumed to be CSF in the soft tissues of the upper neck (arrows). The patient recovered after surgery despite the fact that although myelography revealed a leak, the exact site could not be found at operation.

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B

FIG 18-34 A, Focal linear dura-arachnoid enhancement characterizes this right tentorial en plaque meningioma. B, In another patient, sagittal T1-weighted image of the thoracic spine demonstrates an enhancing intradural extramedullary mass with dural thickening (arrows) demonstrating the meningeal origin of the mass.

Previous radiation therapy for another disease has been connected with some sarcomas.7 The most common primary tumor arising from the leptomeninges is meningioma141 (Figs. 18-34 and 18-35). Meningiomas originate from meningothelial cells of the arachnoid.141 A hormonal inluence has been implicated in the pathogenesis of meningiomas, because they are more common in women than in men, occur more often in patients with breast cancer, and may become symptomatic during pregnancy.14,81,141 Radiation therapy has also been implicated as a causative factor in meningioma,53,152 especially in patients treated for tinea capitis or vascular nevi in childhood. Fifty percent of meningiomas are isointense with gray matter on T1-weighted and T2-weighted imaging; the remaining half vary in signal intensity.151 Heterogeneous signal intensity on MRI may result from calciied, vascular, or cystic components.151 Additional primary leptomeningeal neoplasms such as glioma37,77,98,129 (Fig. 18-36), melanoma,5 melanocytoma114 (Fig. 18-37), sarcoma,131,141 and lymphoma96 are very rare. Primary leptomeningeal gliomas probably originate from heterotopic rests of glial tissue within the meninges and SAS.31,174

Secondary Involvement Breast carcinoma, lymphoma, leukemia, lung carcinoma, malignant melanoma, gastrointestinal carcinoma, and genitourinary carcinoma are the most common neoplasms to progress to meningeal dissemination.74,122,165 Primary CNS neoplasms such as medulloblastoma and primitive neuroectodermal tumor (PNET), pineoblastoma (Fig. 18-38), ependymoma, germ cell tumor (Fig. 18-39), astrocytoma (Fig. 18-40), and glioblastoma (Fig. 18-41) also have a propensity for meningeal spread.8,9,123,124,128 Most tumors tend to produce focal involvement in a dura-arachnoid or pia-SAS distribution. Exceptions to this are aggressive tumors such as lung and breast carcinoma, which may result in diffuse meningeal neoplasm.

Risk Factors for Leptomeningeal Dissemination of Neoplasm The risk factors for leptomeningeal dissemination differ somewhat for primary CNS and non-CNS neoplasms but are largely related to tumor dedifferentiation and proximity to CSF spaces. Characteristics of primary CNS neoplasms that correlate highly with a tendency to CSF spread are (1) poor glial ibrillary acidic protein (GFAP) staining, indicating poor differentiation of neoplasm,123 and (2) close proximity to CSF spaces.60,162 Patient risk factors for leptomeningeal dissemination of primary CNS neoplasm include extended survival9 and previous operation (see Fig. 18-41).8,10 In cases of non-CNS neoplasm, prolonged survival120,122,176 and the presence of other metastatic foci16,120,159 increase the probability of meningeal dissemination. Dispersion of non-CNS neoplastic cells is likely a multistep process according to the analysis of the pathways of metastases performed by Viadana and colleagues.163 This “cascade” phenomenon postulates that spread of the primary tumor occurs to at least one intermediate organ, from which it may disseminate widely.163 The observation that vertebral body (especially in breast carcinoma),16,159 bone marrow, and liver metastases (especially in lung carcinoma)120 are commonly present in cases of meningeal carcinomatosis lends credence to this predisposition of tumors to spread irst to an intervening organ before disseminating widely. The breast, lung, and stomach, in addition to melanoma, are primary sites of solid tumors that tend to metastasize to the leptomeninges.74,75,122,165 More recently, speciic biological subtypes of neoplasms have been identiied that indicate increased risk for developing meningeal carcinomatosis over other subtypes. This phenomenon has been particularly well established in breast carcinoma: the “triple negative” (estrogen receptor, progesterone receptor, HER2 receptor negative) and lobular subtypes demonstrate a propensity to leptomeningeal dissemination.118 As a result of increasingly targeted treatment options, breast carcinoma

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B FIG 18-35 Meningiomatosis in neuroibromatosis type 2 (NF2). A, Axial CT image demonstrates bilateral soft tissue plaques with calciication (arrow). B, Axial T1-weighted image reveals homogeneously enhancing meningeal plaques extending along the bilateral convexities and falx, which represent multiple meningiomas.

A

B FIG 18-36 Primary leptomeningeal gliomatosis. This rare primary malignant meningeal neoplasm was diagnosed only at autopsy. There is both linear and nodular enhancement in a pia–subarachnoid space pattern (arrows) on a coronal image (A) and a sagittal enhanced T1-weighted image (B). (Courtesy Bernhard C. Sander, MD, and Tibor Mitrovics, MD, Freie Universitatsklinikum Rudolf Virchow, Berlin, Germany.)

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A

FIG 18-37 Primary leptomeningeal melanocytosis. Sagittal T1-weighted images obtained before (A) and after (B) administration of gadolinium show multiple tiny nodular foci of hyperintensity (arrowheads) along the pial surface of the cervical spinal cord, with enhancement in this case of primary leptomeningeal melanocytosis. There is also an intramedullary lesion (curved arrow).

A

B FIG 18-38 Subarachnoid spread of pineoblastoma. A and B, Coronal enhanced T1-weighted images show the pineal region mass with pia–subarachnoid space enhancement (arrows) in this patient with CSF dissemination of pineoblastoma.

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tumor subtypes also inluence overall survival rates; one study demonstrated improved prognosis for patients with HER2+ tumor types compared with other subtypes, which may have been related to the tumor subtype itself, differences in overall treatment, or be multifactorial.1 Additional tumor characteristics, such as expression of VEGF, also indicate increased risk for leptomeningeal metastases.76 Hematologic neoplasms such as leukemia and lymphoma are also inclined to CSF spread.75

Mechanisms of Meningeal Neoplastic Dissemination Dura The two major mechanisms of spread of neoplasm to the dura are hematogenous dissemination and direct extension. Hematogenous spread. One pathway for neoplasm to reach the dura is as a sequela of bone metastases; this route is common in patients with breast carcinoma. Vertebral bone metastases disseminate hematogenously through Batson’s plexus and then to the intracranial dural venous sinuses159 (Fig. 18-42). For example, dural metastases are as likely as parenchymal brain metastases in cases of disseminated breast carcinoma, relecting the high incidence of vertebral involvement.159 Direct extension. A second route is dural iniltration, with neoplasm extending directly from vertebral or calvarial lesions2 (Fig. 18-43).

Leptomeninges

FIG 18-39 Disseminated germ cell tumor. This pineal region neoplasm demonstrates ependymal and subarachnoid spread involving the optic chiasm (arrowheads) on an enhanced coronal T1-weighted image.

A

The major mechanisms of seeding into the CSF and leptomeninges are also hematogenous spread and direct extension, but these may take a variety of forms. Hematogenous spread. There are three main modes by which neoplasm is spread hematogenously to the leptomeninges and CSF. First, the choroid plexus may become seeded hematogenously, resulting in tumor deposits that are then sloughed into the CSF.38,61,74,75 This pathway is presumably more common than is clinically evident. The frequency of choroid metastases is likely to be underestimated on MRI, because the normal choroid plexus is irregular in contour. Metastases occur frequently when the choroid plexus is sectioned at pathologic examination; however, the choroid plexus may not be examined routinely.112,122 The second hematogenous route is via parenchymal blood vessels in the Virchow-Robin (perivascular) spaces to the pia mater and then into the SAS (see Fig. 18-2).57,75 This mechanism of seeding of the

B FIG 18-40 CSF spread of astrocytoma in a 30-year-old patient. Sagittal T1-weighted images obtained before (A) and after (B) gadolinium administration show such extensive enhancement of the subarachnoid space that the enhanced T1-weighted image mimics a T2-weighted sequence. The patient had been treated for astrocytoma 3 years earlier.

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B

A

FIG 18-41 CSF spread of glioblastoma multiforme after biopsy in a 40-year-old patient. Six weeks after stereotactic biopsy, an enhanced coronal T1-weighted image shows the primary right thalamic glioblastoma and extensive thick dissemination of neoplasm in a pia–subarachnoid space pattern.

FIG 18-43 Focal direct extension of breast carcinoma calvarial metastasis to dura. Coronal enhanced T1-weighted image shows focal dural thickening (arrows) and enhancement deep to a calvarial focus of breast carcinoma (see also Fig. 18-20).

FIG 18-42 Diagram of the route of hematogenous spread to dura via Batson’s plexus. (From Fukui MB, et al: MR imaging of the meninges: Part 2. Neoplastic disease. Radiology 201:605–612, 1996.)

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leptomeninges and SAS may result in tumor spread either to or from the SAS.57,75,112 Third, neoplasm may interrupt the thin walls of microscopic vessels in the arachnoid to enter the SAS (see Fig. 18-2).134 This pathway of spread occurs more commonly in leukemia and lymphoma than in solid tumors.134 Direct extension. Direct extension, the other major means by which neoplasm gains access to the leptomeninges, can also take one of three forms. First, parenchymal neoplasm close to CSF borders, such as cortical or subependymal tumor, may shed cells into the CSF (see Fig. 18-12).38,172 Non-CNS neoplasms may induce a ibrous reaction that tends to prevent CSF spread; thus, this pathway may be more common among tumors of CNS origin.74,122 Second, an overlying dural neoplasm may invade the leptomeninges directly.64,74,75 Third, spinal epidural neoplasm can spread contiguously along nerve roots or their lymphatics.12,16,38,92,122,159 This route of spread is somewhat controversial; some authors assert that the frequency of leptomeningeal carcinomatosis would be greater if this were an important pathway, considering the common occurrence of vertebral metastases.74

Complications of Meningeal Neoplasms Once the CSF has been seeded, neoplasm has the potential to disseminate widely from a focus in the leptomeninges, throughout the arachnoid and pia mater, through the perivascular (Virchow-Robin) spaces, or along the sleeves of cranial nerves and spinal nerve roots.61 Extension into the perivascular spaces or partial obstruction of the vessel lumen by tumor cells can result in ischemic complications of leptomeningeal carcinomatosis122,165 (Fig. 18-44). The term carcinomatous

A

encephalitis refers to the rare occurrence of diffuse perivascular (Virchow-Robin space) iniltration resulting in ischemia.74,102 Neoplasm adjacent to the meninges or a small site of meningeal tumor involvement may also provoke a diffuse ibrous response of the meninges.122 Because both the meningeal reaction to neoplasm and the neoplasm itself usually enhance on MRI, this inding is not speciic.

SUMMARY A wide spectrum of nonneoplastic and neoplastic conditions may affect the meninges. MRI with FLAIR sequences or enhanced T1-weighted images is an effective modality for characterizing meningeal pathology. The cardinal MRI indings in meningeal disease are hydrocephalus and smooth or nodular enhancement or signal abnormality of the dura-arachnoid, the pia mater–SAS, and the ependyma of the brain or spine. Two major patterns of disease are identiied: a dura-arachnoid pattern that follows along the inner table of the calvarium, and a pia mater–SAS pattern that extends into the sulcal spaces. Nodular disease in particular may suggest neoplasm. Meningeal neoplasm may be clinically silent, and false-negative results on CSF cytologic study are common.8,10,15,122 The addition of MRI to the clinical data and CSF examination may increase detection of meningeal involvement and may allow tumor staging. Understanding the routes of neoplastic spread to the meninges permits identiication of imaging features of the primary tumor that predispose to CSF dissemination, such as proximity to the SAS or ventricles. Although there is considerable overlap in the MR appearance of meningeal involvement in various diseases, the pattern and distribution of enhancement may provide guidance for diagnosis, management, and treatment monitoring of disorders affecting the

B FIG 18-44 Carcinomatous encephalitis. A, Axial CT of the head obtained before contrast medium shows hypoattenuation in the posterior parietal lobe (arrowheads) in a 42-year-old patient who presented with a 4-month history of seizures. B, After contrast administration, pial enhancement is minimal (arrowheads). The patient was initially thought to have subarachnoid hemorrhage, but autopsy showed extensive adenocarcinoma in the perivascular spaces and meninges, with multiple ischemic foci in the brain and a primary focus in the lung.

CHAPTER 18 meninges. Correlation of imaging indings with clinical and CSF data is essential to ensure that treatable disease is not overlooked. Recognition of meningeal neoplasm is increasingly important as treatment options targeted to speciic tumor subtypes allow the potential for prolonged survival.

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126. Osaka K, Handa H, Matsumoto S, et al: Development of the cerebrospinal luid pathway in the normal and abnormal human embryos. Childs Brain 6:26–38, 1980. 127. Paako E, Patronas N, Schellinger D: Meningeal Gd-DTPA enhancement in patients with malignancies. J Comput Assist Tomogr 14:542–546, 1990. 128. Packer R, Siegel K, Sutton L, et al: Leptomeningeal dissemination of primary central nervous system tumors of childhood. Ann Neurol 18:217–221, 1985. 129. Park J, Van den Noort S, Kim R, et al: Primary diffuse leptomeningeal gliomatosis with signs of increased intracranial pressure and progressive meningeal enhancement on MRI. J Neuroimaging 6:250–254, 1996. 130. Partington C, Graves V, Hegstrand L: Meningioangiomatosis. AJNR Am J Neuroradiol 12:549–552, 1991. 131. Pluger T, Weil S, Weis S, et al: MRI of primary meningeal sarcomas in two children: Differential diagnostic considerations. Neuroradiology 39:225–228, 1997. 132. Phillips M, Ryals T, Kambhu S, et al: Neoplastic vs inlammatory meningeal enhancement with Gd-DTPA. J Comput Assist Tomogr 14(4):536–541, 1990. 133. Praharaj S, Sharma M, Prasad K, et al: Unilateral meningeal thickening: A rare presentation of tuberculous meningitis. Clin Neurol Neurosurg 99:60–62, 1997. 134. Price R, Johnson W: The central nervous system in childhood leukemia: I. The arachnoid. Cancer 31:520–533, 1973. 135. Provenzale J, Allen N: MR indings in Wegener’s granulomatosis. ASNR Proceedings Book:130, 1995. 136. Pui M, Langston J, Arai Y: Gd-DTPA Enhancement of CSF in meningeal carcinomatosis. J Comput Assist Tomogr 17:940–944, 1993. 137. Quest D, Salcman M: Fibromatosis presenting as a cranial mass lesion. J Neurosurg 44:237–240, 1976. 138. Rando T, Fishman R: Spontaneous intracranial hypotension: Report of two cases and review of the literature. Neurology 42:481–487, 1992. 139. Runge V, Clanton J, Price A, et al: Dyke Award. Evaluation of contrastenhanced MR imaging in a brain-abscess model. AJNR Am J Neuroradiol 6(2):139–147, 1985. 140. Runge V, Wells J, Williams N, et al: Detectability of early brain meningitis on MR images with pathologic correlation. Radiology 197P:480, 1995. 141. Russell D, Rubinstein L: Pathology of tumours of the nervous system, ed 5, London, 1989, Edward Arnold. 142. Sage M: Blood-brain barrier: Phenomenon of increasing importance to the imaging clinician. Am J Neuroradiol 3:127–138, 1982. 143. Sage M, Wilson A: The blood-brain barrier: An important concept in neuroimaging. AJNR Am J Neuroradiol 15:601–622, 1994. 144. Sakamoto S, Kitagaki H, Ishii K, et al: Gadolinium enhancement of the cerebrospinal luid in a patient with meningeal ibrosis and cryptococcal infection. Neuroradiology 39:504–505, 1997. 145. Sarnat H, Netsky M: Evolution of the nervous system, ed 2, New York., 1981, Oxford University Press. 146. Seltzer S, Mark A, Atlas S: CNS sarcoidosis: Evaluation with contrastenhanced MR imaging. AJNR Am J Neuroradiol 12:1227–1233, 1991. 147. Sherman J, Stern B: Sarcoidosis of the CNS: Comparison of unenhanced and enhanced MR images. AJNR Am J Neuroradiol 11:915–923, 1990. 148. Singer M, Atlas S, Drayer B: Subarachnoid space disease: Diagnosis with luid-attenuated inversion-recovery MR imaging and comparison with gadolinium-enhanced spin-echo MR imaging—Blinded reader study. Radiology 208:417–422, 1998. 149. Smirniotopoulos J, Murphy F: The phakomatoses. AJNR Am J Neuroradiol 13:725–746, 1992. 150. Southwick F, Richardson E, Swartz M: Septic thrombosis of the dural venous sinuses. Medicine 65:82–106, 1986. 151. Spagnoli M, Goldberg H, Grossman R, et al: Intracranial meningiomas: High-ield MR imaging. Radiology 161:369–375, 1986. 152. Spallone A, Gagliardi F, Vagnozzi R: Intracranial meningiomas related to external cranial radiation. Surg Neurol 12:153–159, 1979.

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153. Stern B, Krunholz A, Johns C, et al: Sarcoidosis and its neurological manifestations. Arch Neurol 42:909–917, 1985. 154. Sze G: Diseases of the intracranial meninges: MR imaging features. AJR Am J Roentgenol 160:727–733, 1993. 155. Sze G, Soletsky S, Bronen R, et al: MR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis. AJNR Am J Neuroradiol 10:965–975, 1989. 156. Tishler S, Williamson T, Mirra S, et al: Wegener granulomatosis with meningeal involvement. AJNR Am J Neuroradiol 14:1248–1252, 1993. 157. Tokumaru A, O’uchi T, Tsuneyoshi E, et al: Prominent meningeal enhancement adjacent to meningioma on Gd-DTPA-enhanced MR images: Histopathologic correlation. Radiology 175:431–433, 1990. 158. Truwit C, Barkovich A: Pathogenesis of intracranial lipoma: An MR study in 42 patients. AJR Am J Roentgenol 155:855–864, 1990. 159. Tsukada Y, Fouad A, Pickren J, et al: Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52(12):2349–2354, 1993. 160. Twijnstra A, Van Zanten A, Nooyen W, et al: Cerebrospinal luid beta2-microglobulin: A study in controls and patients with metastatic and non-metastatic neurological disease. Eur J Cancer Clin Oncol 22:387–391, 1986. 161. van de Langerijt B, Gijtenbeek JM, de Reus HP, et al: CSF levels of growth factors and plasminogen activators in leptomeningeal metastases. Neurology 67:114–119, 2006. 162. Vertosick F, Selker R: Brainstem and spinal metastases of supratentorial glioblastoma muliforme: A clinical series. Neurosurgery 27:516–522, 1990. 163. Viadana E, Bross I, Pickren JW: Cascade spread of blood-borne metastases in solid and nonsolid cancers of humans. In Weiss L, Gilbert HA, editors: Pulmonary metastasis, Boston, 1978, GK Hall, pp 142–167. 164. Vogl T, Stemmler J, Bergman C, et al: MR and MR angiography of Sturge-Weber syndrome. AJNR Am J Neuroradiol 14:417–425, 1993. 165. Wasserstrom W, Glass J, Posner J: Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients. Cancer 49:759–772, 1982. 166. Watanabe M, Tanaka R, Takeda N: Correlation of MRI and clinical features in meningeal carcinomatosis. Neuroradiology 35:512–515, 1993.

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19 Demyelinating Disease and Leukoencephalopathies John P. Nazarian, Leo Wolansky, Amit Gupta, and Michael Coffey

INTRODUCTION The white matter of the central nervous system (CNS) is made up of myelinated neuronal axons. Myelin is a dielectric material composed in large part of lipids; it allows for rapid propagation of nerve impulses and is critical for normal development and functioning of the nervous system. Myelination begins early in the second trimester of fetal development and is largely complete by the end of the second year of postnatal life, although some myelination continues into adolescence. Destruction of myelin, or demyelination, is the pathologic hallmark of several neurologic diseases. The prototypical demyelinating disease is multiple sclerosis, one of the most common causes of neurologic disability in young adults. Advances in imaging, particularly magnetic resonance imaging (MRI), have allowed radiologists to play an increasing role in both the initial diagnosis and treatment monitoring of patients with this disease. Other demyelinating diseases, including acute disseminated encephalomyelitis and progressive multifocal leukoencephalopathy, are seen in association with infections and immunologic phenomena. MRI plays an important role in diagnosing these diseases and distinguishing them from other conditions. The disease entities in this chapter are broadly grouped by etiology. In addition to the demyelinating diseases mentioned above, this chapter also covers several other white matter diseases, or leukoencephalopathies. These diverse pathologic processes have different causes but share in common their propensity to cause white matter abnormalities often visible on diagnostic imaging studies. A basic understanding of their imaging characteristics, when combined with a thorough clinical workup, will facilitate accurate diagnosis and appropriate management. Prior to any discussion of imaging of white matter diseases, an important caveat must be given: not all computed tomography (CT) hypodensities and T2/FLAIR (luid-attenuated inversion recovery) hyperintense foci in the white matter indicate demyelinating disease. White matter signal changes on MRI are very common in the elderly and increase in prevalence with age. These so-called unspeciic bright objects (UBOs) are not without clinical relevance in elderly patients; they have been associated with an increased risk of cognitive decline, dementia, and stroke.72 Other causes of T2-hyperintense white matter lesions include migraines and sequelae of cerebrovascular disease.29

MULTIPLE SCLEROSIS Multiple sclerosis (MS) is the most common demyelinating disease of the CNS. MS usually presents between the ages of 20 and 50 and is three times more common in women than in men.27,48 The hallmark of the disease is multiplicity in time and space.59 In most cases, patients present with a subacute clinically isolated syndrome; common presentations include optic neuritis, motor and sensory

deicits, transverse myelitis, and brainstem syndromes.47,52 The McDonald criteria, revised in 2010, allow for diagnosis of MS based on various clinical and paraclinical assessments, including MRI.54 Several MS subtypes (clinical phenotypes) have been deined on the basis of their clinical course; these deinitions were most recently revised in 2013 and play an important role in disease prognostication and design of clinical trials.40 The pathophysiology of MS is complex and not fully understood but is likely autoimmune in nature. The main pathologic characteristic of the disease is the demyelinated plaque, a lesion induced by a variety of immune mechanisms.34 Plaques are responsible for the characteristic hyperintense white matter abnormalities visible on conventional luid-sensitive MR sequences.18 In addition, more advanced MR techniques have permitted detection of other abnormalities in the so-called normal-appearing white matter (NAWM)62 and gray matter that also occur in MS.15,23 MRI is the imaging method of choice in the diagnosis and monitoring of MS, owing to its high sensitivity and speciicity44 as well as its ability to detect or exclude possible alternative conditions. CT is limited in use where MRI is available. The MRI criteria integrated into the McDonald criteria have demonstrated a high speciicity for subsequent development of MS in patients who present with a clinically isolated syndrome suggestive of MS.12 In such patients the MRI protocol should always include T2-weighted and FLAIR sequences, preferably with three-dimensional (3D)-Fourier transform (volumetric) to minimize partial volume averaging in the commonly small lesions. MS lesions are seen in characteristic locations: where the white matter contacts the cerebrospinal luid (CSF). Periventricular, optic nerve, spinal cord, and supericial brainstem lesions are typical, including the cerebellar peduncles, near the trigeminal root entry zone, the tectum, and fourth ventricular loor. Corpus callosum lesions are also characteristic and are much more common in MS than in other white matter diseases.29,63 MS lesions have a characteristic size and shape. On T2-weighted and FLAIR images, demyelinating plaques in the brain appear as highintensity lesions that are often 10 to 15 mm in size and ovoid, although this shape disappears in more advanced cases when lesions become conluent (Fig. 19-1). Periventricular lesions tend to be oriented with their major axis perpendicular to the ependymal surface, referred to as Dawson’s ingers (Fig. 19-2). Periventricular and juxtacortical lesions are better delineated on FLAIR images.19 T1-weighted images are generally less sensitive for detection of plaques, but a subset of T2-hyperintense lesions appear dark on T1 images. These “black holes” have signal characteristics ranging from mildly to severely hypointense; the degree of hypointensity correlates with the degree of pathologic severity.19,71 When persistent, these lesions are associated with demyelination and axonal loss and have been used in clinical trials as markers of accumulated disease burden.18 Degree of T1-hypointensity is also inluenced by scanning technique (Fig. 19-3).

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FIG 19-1 FLAIR transaxial image cropped for the right cerebral hemisphere. Characteristic ovoid lesions are commonly 10 to 15 mm in size.

B FIG 19-2 Sagittal MRI of two different patients with MS. T2 (A) and FLAIR images (B). Multiple ovoid lesions with the long axis perpendicular to the ventricular surface, “Dawson’s ingers.” (B from Bakshi R, et al: The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis. Neurology 63[Suppl 5]: S3–S11, 2004.)

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FIG 19-3 Transaxial T1-weighted images of the right cerebral hemisphere. T1-weighted (A), T1 with fat saturation and Gd (B), and T1 with fat saturation without Gd (C). Noncontrast T1 reveals the presence of a white matter hypointense lesion (arrowhead in A), which on contrast-enhanced image appears to enhance (B). Noncontrast fat-suppressed T1-weighted image reveals that the hyperintensity (arrow in C) is due to fat suppression and not contrast administration due to magnetization transfer effect.

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FIG 19-4 Contrast-enhanced images with standard 0.1 mmol/kg Gd dose (A) and cumulative 0.3 mmol/kg dose (B). Triple-dose image (arrow in B) reveals an enhancing lesion that was not seen with single dose (arrow in A).

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FIG 19-5 Axial T1 with Gd (A) and FLAIR (B). The size of the ring-enhancing lesion of left middle cerebellar peduncle is seen to match the size of FLAIR hyperintensity—unlike most ring lesions, for which the area of perifocal edema on FLAIR is signiicantly larger than the enhancing focus.

In addition, lesion enhancement is considered an excellent surrogate for disease activity after a study revealed contrast enhancement was associated with active inlammation in 40 of 40 pathologically proven cases.51 Triple-dose (0.3 mmol/kg) delayed imaging (20-40 minutes) has shown an increase of more than two times the enhancing lesion detection rate (Fig. 19-4) but is not standard, given concerns about nephrogenic systemic ibrosis.76,77 Enhancement of lesions may be homogeneous or ringlike.56 A differential feature from ring lesions of many other etiologies is the margin of enhancement coinciding with the margin of FLAIR signal rather than extending signiicantly beyond the enhancing border (Fig. 19-5).

Most lesions are up to 1.5 cm in diameter, but in rare cases larger ring-enhancing lesions may be seen with obvious mass effect (tumefactive demyelination) (Fig. 19-6). A characteristic feature is an openring appearance thought to represent a front of demyelination. In tumefactive cases, perfusion imaging can be of value because ringenhancing malignant neoplasms typically display elevation of relative cerebral blood volume (rCBV) and rCBV ratio, whereas demyelination does not (Fig. 19-7). The “life cycle” of an MS lesion typically includes a short enhancing phase, the majority enhancing for no more than 8 weeks. Oftentimes the enhancement of each lesion appears independent of the others (Fig. 19-8).

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FIG 19-6 Axial T1 images; baseline without Gd (A) and with Gd (B). C, Follow-up several months later (with Gd). Noncontrast image (A) displays obvious edema with sulcal effacement. Postcontrast image (B) reveals nonspeciic-appearing tumefactive ring-enhancing lesion. Follow-up (C) demonstrates complete regression.

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FIG 19-7 Three lesions in same patient with perfusion images (A, C, E), with corresponding Gd-T1 images (B, D, F). Each lesion is larger than typical MS plaque but demonstrates open ring of enhancement and low relative cerebral blood volume (rCBV) (light blue open-ring in A, C, E). Ratio of lesion to control brain was approximately equal to 1. On follow-up, the lesions resolved.

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FIG 19-8 Gd-T1 on 6 consecutive months in same patient. Several enhancing lesions present on the initial scan (A) resolve by 1 month later (B), while new lesions appear. Those lesions, in turn, disappear within 1 month (C), by which time new lesions appear (D). Two months later another new lesion appears (E), which is gone within 1 month (F).

With the development of immunomodulatory treatment, MRI is periodically used (e.g., annually) even in clinically stable patients to monitor therapeutic eficacy. Contrast enhancement or interim development of new nonenhancing FLAIR lesions are considered by many to indicate failure to arrest disease. Although MS is the epitome of white matter disease, more recently developed sequences (including volumetric T1, FLAIR, and double-inversion recovery) have revealed signiicant gray matter involvement.15,23

In addition to the characteristic relapsing-remitting clinical pattern, MS can also be a progressive diffuse degenerative disease. This is manifest as cerebral atrophy and abnormalities in NAWM. Magnetization transfer contrast62 and diffusion tensor imaging (DTI)16 have shown measurable differences in the white matter of MS vs. healthy controls that were imperceptible to visual inspection. Functional (f)MRI has also been used to study connectivity abnormalities associated with cognitive dysfunction.24

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VIRAL AND POSTVIRAL DEMYELINATING SYNDROMES Acute Disseminated Encephalomyelitis Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the CNS that commonly follows a febrile illness such as an upper respiratory infection. Numerous infectious agents— predominantly viruses but also several bacterial species—have been reported in association with ADEM. Less commonly the disease may occur following a vaccination. Children with ADEM commonly present with nonspeciic symptoms such as fever, headache, and lethargy; adults are more likely to have motor and sensory deicits, as might be seen with an acute episode of MS.14,46,68 Though they can present in similar fashion, distinction between ADEM and MS is critical because of different prognostic and thera-

peutic implications for the patient. ADEM is more common in children and, unlike MS, is typically monophasic rather than relapsing. There are also underlying pathologic differences: though the lesions of both MS and ADEM are due to immune-mediated inlammation and demyelination, in ADEM the demyelination remains restricted to the perivascular area, unlike the conluent demyelination observed in MS.46 MRI is generally considered the most valuable diagnostic tool in the workup of suspected ADEM.46 T2-weighted and FLAIR images demonstrate multiple asymmetric hyperintense white matter lesions, particularly in the subcortical regions (Fig. 19-9). Periventricular and corpus callosum lesions are less common than in MS. Enhancement of lesions on postcontrast images is variable; larger lesions may show peripheral or focal irregular central enhancement.29 Spinal cord lesions can also be seen but are uncommon.10

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FIG 19-9 Acute disseminated encephalomyelitis. A and B, Initial axial FLAIR images in this 32-year-old man who presented with numbness in his lower extremities, fever, and headache demonstrate numerous hyperintense foci in the subcortical white matter bilaterally. C, Post-Gd T1 images demonstrate enhancement of several of these lesions. Corresponding FLAIR (D and E) and post-Gd T1 (F) images obtained 2 months later (after steroid therapy and plasma exchange) showed resolution of most lesions.

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Given the overlap in MRI appearance between the two conditions, it is not always possible to distinguish ADEM from MS on a single MRI examination. For this reason, follow-up scans with an interval of at least 6 months are very helpful; lesions that resolve after corticosteroid therapy or remain unchanged suggest ADEM, but new lesions raise concern for MS.29,30

Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that results from an opportunistic infection of oligodendrocytes by a type of human polyomavirus called the JC virus. The disease occurs in the setting of immunosuppression; although irst described

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in patients with Hodgkin’s disease and chronic lymphocytic leukemia, it has been most frequently associated with human immunodeiciency virus (HIV) infection. PML can also be seen in the context of biologic and immunomodulating therapies, such as natalizumab for MS.26,29 Patients usually present with insidious onset of neurologic deicits that may affect motor function, speech, vision, personality, and cognition.39 MRI indings in PML include multiple hyperintense foci in the subcortical white matter on T2-weighted and FLAIR images. These lesions are frequently bilateral and characteristically involve the subcortical U ibers (Fig. 19-10). The parietal, occipital, and frontal lobes are commonly affected; other common sites include the posterior fossa and the deep gray matter nuclei.29,69,75

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FIG 19-10 Progressive multifocal leukoencephalopathy. FLAIR images (A) obtained in this HIV patient showed asymmetric subcortical white matter signal changes in the left and right parietal white matter without signiicant enhancement visible on post-Gd T1 images (B). One month later, corresponding FLAIR and contrast-enhanced (C and D) images demonstrate progression of white matter changes (including involvement of the splenium of the corpus callosum) but still no signiicant lesion enhancement.

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FIG 19-11 Progressive multifocal leukoencephalopathy—immune reconstitution inlammatory syndrome. A, Axial FLAIR images in this 31-year-old woman with HIV (viral load > 80,000 copies/mL) at her hospital presentation for weakness show asymmetric subcortical white matter hyperintensity in the left frontal lobe, which involves the U ibers. Follow-up images obtained 2 (B) and 14 months (C) later (after initiation of combined antiretroviral therapy) show progression, with eventual involvement of the contralateral hemisphere. D-F, Corresponding post-Gd T1 images show progressive enhancement over time, suggesting an evolving inlammatory process.

Other MRI features of PML allow distinction from other neurologic complications of the immunosuppressed state, including cerebral abscess, toxoplasmosis, and primary CNS lymphoma. PML lesions do not demonstrate mass effect or associated edema, differentiating them from these other conditions. Additionally, contrast enhancement is usually absent in PML lesions, unlike the ringlike enhancement commonly seen in cerebral abscesses or toxoplasmosis.55 Special note should be made of an entity known as immune reconstitution inlammatory syndrome (IRIS or PML-IRIS), commonly observed in HIV-positive patients with PML undergoing combination antiretroviral therapy. This condition is due to a reconstituted immunity, allowing iniltration of lymphocytes into PML lesions, with corresponding CNS inlammation. In cases of PML-IRIS, PML lesions may demonstrate mass effect and gadolinium (Gd) enhancement (Fig. 19-11).74

HIV Leukoencephalitis CNS manifestations of HIV infection include those related to primary HIV infection, those related to opportunistic infections, and those that result from neoplastic or vascular complications.41 We will focus here on the effects of primary HIV infection. Neuroimaging indings in HIV patients may be completely normal. In patients with indings of HIV encephalitis, early MRI indings include symmetric multifocal T2-hyperintense lesions in the periventricular white matter and centrum semiovale, which generally spare the subcortical U ibers.6 Chronic HIV infection results in progression of these changes, with the initially patchy T2-hyperintense lesions becoming more conluent and extensive, sometimes extending to involve the basal ganglia, cortex, cerebellum, brainstem, and spine. The white matter lesions are typically slightly

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FIG 19-12 HIV leukoencephalitis. A and B, Axial T2-weighted images acquired 12 months apart in this 57-year-old man with HIV show extensive symmetric and conluent white matter signal abnormalities. Even when accounting for slight differences in slice position, progression of cerebral atrophy in the interval between the scans was perceptible.

hypointense on T1 images and usually do not enhance. Another prominent feature of chronic HIV infection is progressive cerebral atrophy41 (Fig. 19-12).

TOXIC AND TRAUMATIC LEUKOENCEPHALOPATHIES Pathologic alteration of the cerebral white matter can be caused by exposure to a variety of agents, such as cranial irradiation, chemotherapeutic agents (including antineoplastic and immunosuppressive drugs), drugs of abuse, environmental toxins, and physical trauma. Clinical indings are highly variable; however, patients often present with neurobehavioral deicits ranging from inattention, forgetfulness, and personality changes to severe neurologic dysfunction, which can be easily confused with other white matter diseases.20,49

Radiation-Induced Demyelination Radiation injury to the brain is commonly seen as a complication of therapeutic radiation therapy for intracranial disease (most commonly primary and metastatic brain tumors, but also arteriovenous malformations) and head and neck neoplasms. It takes two forms: focal injury/radiation necrosis and diffuse white matter injury, also known as diffuse radiation-induced leukoencephalopathy.70

Radiation Necrosis Radiation necrosis (RN) is severe local tissue reaction to high-dose focal radiation therapy and is usually seen at the site of maximum radiation dose—in and around the tumor bed. The reported incidence is 3% to 24%, which increases steeply if doses exceed 65 Gy. RN is most commonly seen 3 to 12 months following radiotherapy, with 70% of cases occurring during irst 2 years, but can rarely develop even decades later.17,70 CT indings are nonspeciic: RN typically appears as a focal hypodensity with mass effect and variable contrast enhancement. MRI

is more sensitive and speciic than CT in evaluating RN, demonstrating T2-weighted and FLAIR hyperintensity with or without irregular contrast enhancement. Differentiation between recurrent neoplasm and RN is a frequent diagnostic dilemma because they share imaging characteristics, including origin at or close to the original tumor site, contrast enhancement, interval growth, and surrounding mass effect. Certain diagnostic clues that favor RN have been described, such as a “soap bubble” or “Swiss cheese–like” pattern of enhancement and periventricular location of the lesion. Conversely, corpus callosum involvement, in conjunction with multiple enhancing lesions with or without extension across the midline and subependymal spread, suggests tumor progression.33,50 In many cases, however, the distinction can still not be made with conventional imaging, owing to the coexistence of tumor and RN. In such cases, advanced imaging techniques like MR perfusion imaging (rCBV, vascular transfer constant [Ktrans]), MR spectroscopy (choline [Cho], creatine [Cr], and N-acetylaspartate [NAA]), and positron emission tomography (PET) may be helpful (Fig. 19-13). Restricted diffusion, elevated rCBV and Ktrans values, high Cho/Cr and Cho/NAA ratios, and high PET uptake are more frequently seen in recurrent tumor than in radiation necrosis.60

Diffuse Radiation-Induced Leukoencephalopathy Diffuse radiation-induced leukoencephalopathy refers to diffuse white matter injury secondary to large-volume or whole-brain radiation. RN and diffuse radiation-induced leukoencephalopathy can be seen concurrently in a patient or may occur sequentially. Typical CT indings are low-attenuation lesions involving the bilateral cerebral hemispheres, without any contrast enhancement or mass effect. The MRI is more sensitive and shows corresponding white matter hyperintensities on T2-weighted and FLAIR sequences. The severity of involvement ranges from small foci at the angles of the frontal and occipital horns to conluent and symmetric involvement of the entire cerebral white matter. More severe abnormalities are

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FIG 19-13 Radiation necrosis. This 35-year-old woman with a biopsy-proven WHO grade II right temporal oligodendroglioma was treated with resection and subsequent radiation therapy. A, Post-Gd T1-weighted image demonstrates multiple irregular foci of enhancement in the right frontal centrum semiovale. B, The corresponding corrected rCBV map fails to show elevated perfusion related to the right frontal abnormal enhancement. C, The corresponding FDG-PET image demonstrates asymmetrically diminished activity in the right frontal lobe, favoring radiation-induced changes over viable neoplasm. D, Six-month follow-up post-Gd T1-weighted image following treatment with hyperbaric oxygen therapy shows almost complete resolution of the right frontal enhancement, conirming the diagnosis of radiation necrosis.

noted with increase in patient age, volume of brain irradiated, radiation dose, and interval between radiotherapy and imaging. In most cases, the indings are indistinguishable from white matter changes seen with other leukoencephalopathies.42,70

Disseminated Necrotizing Leukoencephalopathy Disseminated necrotizing leukoencephalopathy (DNL) refers to diffuse white matter injury following treatment with intrathecal or systemic

chemotherapeutic agents. This condition was irst reported in children with leukemia who were treated with intrathecal methotrexate, but several other agents, including BCNU, melphalan, ludarabine, cytarabine, 5-luorouracil, levamisole, and cisplatin, have also been implicated.13,35 The prevalence of injury increases substantially when chemotherapy and radiation therapy are used together. However, the latent period between treatment and onset of symptoms is shorter after chemotherapy than after radiation.36,70

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FIG 19-14 Acute methotrexate neurotoxicity. MRI was performed after this 23-year-old man undergoing methotrexate therapy for acute lymphoblastic leukemia began to experience facial hemiparesis and speech dificulties. DWI (A and B) obtained 16 hours apart demonstrate asymmetric ovoid regions of diffusion restriction involving the left and right centrum semiovale; interestingly the laterality of the imaging pattern reversed on the second exam. The axial FLAIR image (C) corresponding to image A reveals no appreciable abnormality. (Images courtesy Vasant Garg, MD and Stephanie Soriano, MD.)

The pathologic indings in DNL resemble those of radiationinduced white matter change and include axonal swelling, multifocal demyelination, coagulation necrosis, and gliosis. The clinical presentation and imaging appearance of DNL is also similar to diffuse radiationinduced leukoencephalopathy. In mild cases, both MRI and CT scan show diffuse symmetric bihemispheric white matter changes that are usually subclinical and transient and indistinguishable from diffuse radiation injury. However, in severe cases there is rapid neurologic deterioration, and imaging may demonstrate lesions with intense tumorlike solid enhancement and associated mass effect.35,70 Methotrexate has speciically been implicated as a causative agent when acute neurotoxicity is seen in patients who have been treated for leukemia and lymphoma. Diffusion-weighted imaging (DWI) allows early detection of white matter injury in these patients. Typical indings include asymmetric bilateral diffusion restriction in the deep hemispheric white matter, commonly in the centrum semiovale (Fig. 19-14). Contemporaneously acquired T2-weighted and FLAIR images often appear completely normal; corresponding regions of increased signal intensity may be seen on follow-up exams several days after presentation.21

Mineralizing Microangiopathy Mineralizing microangiopathy is a neuroradiologic abnormality characterized by intracerebral calciications usually seen after combined radiation and chemotherapy for the treatment of CNS neoplasms in childhood. The calciications are typically seen in the basal ganglia and subcortical white matter (Fig. 19-15) but rarely can also occur in cerebral cortex and the dentate nuclei of the cerebellum. The indings are usually superimposed on diffuse cortical atrophy and white matter changes.37 CT is more sensitive than MRI in detecting the calciications. Areas of calciication generally demonstrate a decreased signal on conventional MRI sequences; this is due to a paucity of mobile protons. Rarely calciication may reveal paradoxically increased signal on T1-weighted images, which has been attributed to a surface relaxation mechanism associated with particulate calcium.61,67

Marchiafava-Bignami Disease Marchiafava-Bignami Disease (MBD) is a progressive disease characterized by demyelination and necrosis of the corpus callosum associated with chronic alcoholism. The condition was irst described in Italian red wine drinkers but is occasionally seen in nonalcoholic patients as well. The disease may have an acute, subacute, or chronic clinical presentation and may lead to death within weeks to months.5 Although CT may reveal hypoattenuation in the corpus callosum, MRI is currently the most sensitive diagnostic tool. The lesions are typically hyperintense on T2-weighted and FLAIR sequences and hypointense on T1-weighted sequences. Lesions most commonly involve the corpus callosum (Fig. 19-16) but may also occur in the adjacent hemispheric white matter and middle cerebral peduncles; the subcortical U ibers are usually spared. The lesions usually do not cause mass effect but may show peripheral enhancement in the acute phase. The chronic lesions have a more cystic appearance. On DWI, diffusion restriction can be seen, which may resolve completely without any apparent permanent damage.25,45,57

HYPOXIC, ISCHEMIC, AND METABOLIC LEUKOENCEPHALOPATHIES The cerebral white matter is susceptible to injury from a variety of processes that deprive it of adequate oxygenated blood supply or cause metabolic derangements. Several of these entities are described in the following sections.

Hypoxic-Ischemic Encephalopathy Inadequate oxygen delivery to the brain can occur in a number of clinical situations, including cardiopulmonary arrest, drowning, carbon monoxide poisoning, and severe anemia.66 Hypoxic brain injury can also be an unfortunate complication of childbirth. In these critically ill patients, imaging can help guide short-term clinical management and in some cases may provide prognostic information.

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FIG 19-15 Cerebral calciications in a similar pattern to mineralizing microangiopathy. These noncontrast CT images obtained in a 79-year-old woman with multiple medical problems demonstrate coarse basal ganglia calciications (A) as well as posterior subcortical and parenchymal calciications (B). Although there was no documented history of chemotherapy or radiation treatment in this patient, the CT appearance is certainly similar to indings seen in mineralizing microangiopathy.

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FIG 19-16 Marchiafava-Bignami disease. MRI (images cropped for splenium) was performed in this 40-yearold woman with alcohol dependence who presented with left-sided sensory deicits. Axial FLAIR image (A) reveals focal increased signal in the splenium of the corpus callosum. Associated abnormal diffusion restriction is seen on DWI (B) and ADC map (C).

CT is frequently the irst imaging study obtained in cases of anoxic or hypoxic brain injury. Typical indings include diffuse brain swelling, relative loss of gray-white matter differentiation, and hypodensity of the basal ganglia. It is vital to remember that these changes can be very subtle and progress over time. The appearance of an initial head CT may be completely unremarkable.66 MRI, particularly DWI,4 is more sensitive for detecting subtle abnormalities in the early phases of brain injury. Findings are described as occurring in four phases: an acute phase (within 24 hours after the hypoxic insult), an early subacute phase (days 1-13), a late subacute phase (days 14-20), and a chronic phase (after 21 days). During the acute and early subacute phases, T2-weighted and DWI sequences show increased signal in the cortex, thalamus, and basal ganglia (Fig. 19-17). In the late subacute phase, the hyperintensity on DWI

fades and diffuse white matter abnormalities may develop. During the chronic phase, the DWI signal has returned to normal and diffuse atrophy and ventricular dilatation is visible.73

Posterior Reversible Encephalopathy Syndrome Posterior reversible encephalopathy syndrome (PRES) has been described as a neurotoxic state accompanied by a unique CT or MRI appearance.7 The clinical manifestations of the syndrome can include a broad range of signs and symptoms, including headache, visual changes, paresis, altered mental status, and generalized seizures.22 Probably the best-known feature of PRES, however, is the symmetric pattern of posterior-predominant bihemispheric cerebral edema visible on CT and MRI studies (Fig. 19-18). PRES has been described in association with a number of conditions, including preeclampsia/

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FIG 19-17 Hypoxic-ischemic encephalopathy. This 2-year-old boy experienced cardiac arrest during surgical removal of a Wilms’ tumor. DWI (A) and ADC map (B) show extensive abnormal diffusion restriction in the bihemispheric white matter and deep gray structures. T2-weighted (C) and FLAIR (D) images show corresponding increased signal.

eclampsia, allogeneic bone marrow and solid organ transplantation, multiple autoimmune diseases, and in cancer patients receiving highdose chemotherapy.7 The pathophysiologic mechanism underlying PRES is still not clearly established and has been a source of controversy. A current popular theory holds that development of vasogenic edema in PRES is due to severe hypertension overwhelming the limits of cerebrovascular autoregulation, resulting in hyperperfusion. This theory is challenged by the fact that in some cases, PRES occurs with only mild or absent elevation of blood pressure. Another, older theory that has received renewed support argues that systemic toxicity leads to endothelial dysfunction, resulting in vasoconstriction and hypoperfusion that gives rise to the characteristic imaging indings.8

Classic imaging indings on CT and MR are of symmetric vasogenic edema, most commonly affecting the parietal and occipital lobes. This edema usually completely resolves and is manifested as conluent hypodensity in the posterior subcortical and deep white matter on CT, with corresponding T2 and FLAIR hyperintensity on MRI. The typical pattern of lesion location follows the distribution of brain watershed zones. A variety of other patterns, however, have been reported in the literature, including edema involving the basal ganglia, cerebellum, and brainstem. Associated hemorrhage and foci of diffusion restriction have also been reported in a minority of cases.7,65

Binswanger’s Disease Binswanger’s disease is a form of subcortical vascular dementia caused by arteriosclerosis affecting small vessels supplying the cerebral white

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FIG 19-18 Posterior reversible encephalopathy syndrome (PRES). A, Emergent head CT was performed for acute hypertension in this 2-year-old girl with a history of severe aplastic anemia undergoing bone marrow transplantation. A symmetric pattern of posterior-predominant vasogenic edema was evident. Also noteworthy is the moderate parenchymal volume loss, likely related to the patient’s other underlying medical conditions. Subsequently obtained T2-weighted (B) and FLAIR (C) MRIs showed symmetric abnormally high signal in the posterior cerebral white matter.

matter. The disease is strongly associated with hypertension and lacunar infarction (>90% of cases). The clinical presentation is characterized primarily by loss of memory and worsening cognitive function; emotional changes and evidence of subcortical dysfunction (e.g., gait abnormalities, incontinence) may also be present.2,53 Diffuse asymmetric hypodensity of the central cerebral white matter is visible on CT studies. MRI indings include T2-hyperintense lesions in the subcortical and periventricular lesions, especially in the frontal horns and centrum semiovale. As mentioned earlier, lacunar infarcts (in the basal ganglia and thalami) are extremely common. Diffuse cerebral atrophy is another consistent inding of this entity.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy CADASIL is an inherited form of vascular dementia that usually presents between ages 30 and 50. Common presentations include migraines and ischemic events, with eventual progression to subcortical dementia.72 The disease has been linked to mutations of the Notch3 gene on chromosome 19, which result in severe changes to vascular smooth muscle cells.28 MRI demonstrates conluent T2-hyperintense areas in the periventricular white matter that become more diffuse over time, with eventual involvement of the external capsule and temporal poles (Fig. 19-19). The basal ganglia and thalamus are also affected, allowing differentiation from MS. Other indings include lacunar infarcts and microhemorrhages.11

Osmotic Demyelination Syndrome Osmotic demyelination syndrome (ODS) refers to central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM). CPM is a syndrome of acute pontine demyelination, originally described in alcoholics1 but most commonly seen in association with electrolyte abnormalities and rapid correction of hyponatremia.31,32,64 Other predisposing conditions include hepatic dysfunction, liver transplantation, and hyperosmolar states.3 The typical clinical course of CPM is marked by neurologic deterioration 2 to 8 days following correction

of hyponatremia; dysarthria and dysphagia occur irst, followed by progression from laccid quadriparesis (corticospinal tract) to spastic quadriparesis (basis pontis). Involvement of the tegmentum may result in pupillary and oculomotor dysfunction. Severe cases may result in “locked in” syndrome.3,64 Although the pontine white matter is most susceptible to this process, extrapontine involvement (EPM) is common and sometimes even occurs independent of CPM. Common presenting symptoms of EPM include behavioral disorders, movement disorders, seizures, polyradiculopathy, and neuropathy.3 Pathologic features of ODS include a symmetric noninlammatory loss of myelin, with preservation of neuronal cell bodies and axons of the central pons and sparing of the peripheral ibers and axons of the corticospinal tract. In cases of EPM, similar indings are seen in other areas, including the cerebellum, lateral geniculate body, external capsule, basal ganglia, thalamus, gray-white junction of the cerebral cortex, and hippocampi.32 MRI has permitted recognition of ODS as it develops and is the most sensitive imaging modality for this entity. DWI is particularly useful for early diagnosis.58 Increased DWI signal with corresponding decreased ADC values in the central pons is characteristically seen in the central pons in a symmetric trident pattern. Increased T2 and FLAIR signal in an identical pattern occurs 7 to 10 days after the appearance of diffusion restriction (Fig. 19-20). There is no mass effect and typically no enhancement of lesions, allowing differentiation from neoplasms and acute MS plaques. In cases of EPM, similar indings occur bilaterally and symmetrically along a similar time course in the aforementioned commonly affected extrapontine locations.3

MISCELLANEOUS Amyloid Leukoencephalopathy Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease caused by deposition of β-amyloid protein in the walls of blood vessels. CAA is usually seen in elderly patients and is well known as a cause

FIG 19-19 CADASIL. FLAIR images in

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this patient with CADASIL show conluent areas of signal hyperintensity in the periventricular white matter (A) and right temporal pole (B). Several lacunar infarcts are also apparent. Foci of acute ischemia are apparent on DWI (C and D).

FIG 19-20 Central pontine myelinolysis. MRI (images cropped for pons) was performed in this 19-year-old liver transplant recipient. T2-weighted (A) and FLAIR (B) images show abnormal signal in the pons with sparing of the corticospinal tracts, resulting in the characteristic “trident” pattern.

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FIG 19-21 Amyloid leukoencephalopathy. This 75-year-old woman was transferred from an outside hospital with altered mental status; the working diagnosis was “possible brain tumor.” A large region of abnormal high signal in the right frontal white matter is evident on T2-weighted and FLAIR images (A and B). Susceptibility-weighted images (C) revealed punctate foci of low signal in the right frontal and left parietal lobes, suggesting microhemorrhages. Pre- and postcontrast T1-weighted images (D and E) failed to show enhancement in the region of T2 signal abnormality. Fused PET/CT images (F) demonstrated decreased FDG uptake corresponding to the region of signal abnormality, adding further evidence that this was not a malignant neoplasm.

of intracerebral hemorrhage. In uncommon cases, an inlammatory manifestation of this disease can result in cognitive decline, headaches, and seizures.9,43 This inlammatory entity, which we call amyloid leukoencephalopathy (also referred to as CAA-related inlammation or cerebral amyloid inlammatory vasculopathy) presents on MRI with areas of high signal intensity in the cerebral white matter, which may be solitary or multifocal and bilateral.38 No contrast enhancement is present.43 The diagnosis may be suggested on gradient echo images, which will allow visualization of associated cerebral microhemorrhages or hemosiderin foci (Fig. 19-21), common indings in CAA.

REFERENCES 1. Adams RD, Victor M, Mancall EL: Central pontine myelinolysis: A hitherto undescribed disease occurring in alcoholic and malnourished patients. AMA Arch Neurol Psychiatry 81(2):154–172, 1959. 2. Akiguchi I, Budka H, Shirakashi Y, et al: MRI features of Binswanger’s disease predict prognosis and associated pathology. Ann Clin Transl Neurol 1(10):813–821, 2014. 3. Alleman AM: Osmotic demyelination syndrome: Central pontine myelinolysis and extrapontine myelinolysis. Semin Ultrasound CT MR 35(2):153–159, 2014.

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20 Orbit Colin S. Poon, Michael Abrahams, and James J. Abrahams

ANATOMY The soft tissue structures of the orbit are contained within a bony cavity and include the globe, extraocular muscles, optic nerve–sheath complex, lacrimal apparatus, and various vascular and nerve structures (Figs. 20-1 to 20-4).

Bony Anatomy The bony orbit is a conical structure with the apex pointing posteriorly. The orbital roof is composed of the frontal bone and is thinner anteriorly. The medial wall is composed of the frontal process of the maxillary bone anteriorly, the lamina papyracea of the ethmoid air cells at the midportion, and the sphenoid bone posteriorly. The lamina papyracea is very thin, and not surprisingly it is a common site of orbital blowout fracture and spontaneous dehiscence of orbital fat. The lateral orbital wall is formed by the orbital surface of the zygomatic bone. The orbital loor is formed by the orbital plate of the maxilla, the orbital process of the palatine bone, and the orbital surface of the zygomatic bone. The orbital plate of the maxilla is thin and a common site of inferior blowout fracture. Multiple foramina and canals go through the bony orbits (Box 20-1) (see Figs. 20-1 and 20-2). The optic canal (also called optic foramen) is located at the orbital apex. It is bordered by two bony spikes of the lesser wing of the sphenoid bone, commonly referred to as the optic struts. The canal contains the optic nerve and ophthalmic artery, both of which are contained within a dural sheath. The superior orbital issure is located at the margin between the lateral wall and the orbital roof. The greater wing of the sphenoid bone forms its lateral boundary, and the lesser wing forms its medial boundary. The superior orbital issure contains the superior ophthalmic vein; the oculomotor (III), trochlear (IV), and abducens (VI) nerves; and the ophthalmic division of the trigeminal nerve (V1). The superior orbital issure forms the largest communication between the orbit and intracranial structures and therefore forms a conduit for infectious or neoplastic processes between the orbital apex and the cavernous sinus. The inferior orbital issure is located at the margin between the lateral wall and the orbital loor. It contains the infraorbital (branch of V2) and zygomatic nerves, the nerve branches from the pterygopalatine ganglion, and venous connection between the inferior ophthalmic vein and the pterygoid plexus. The inferior orbital issure connects with the pterygopalatine fossa and the masticator space/infratemporal fossa, allowing the spread of deep facial infection and neoplasm to the orbital apex. The globe is essentially a spherical structure, with the wall consisting of three layers: retina (innermost), choroids (middle), and sclera (outermost) (Fig. 20-3). These layers cannot be resolved with current

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clinical computed tomography (CT) or magnetic resonance imaging (MRI) technology unless they are separated by pathologic processes (e.g., retinal detachment). The globe is divided into three luid-illed cavities: anterior chamber, posterior chamber, and vitreous cavity.4,43 The anterior chamber and posterior chamber constitute the anterior segment, and the vitreous cavity constitutes the posterior segment. The anterior chamber extends from the cornea to the iris. The posterior chamber extends from the posterior surface of the iris to the anterior surface of the vitreous. The vitreous cavity is posterior to the posterior chamber. The anterior border of the orbit is formed by the orbital septum (see Fig. 20-2D), a ibrous structure adherent to the inner margin of the orbital rim, with central portions that extend into the tarsus of the eyelids. Although there are a few oriices for passage of vessels, nerves, and ducts, the septum forms an effective barrier to prevent supericial processes from extending into the orbit proper. A pathologic process such as cellulitis may be designated as preseptal versus postseptal. A postseptal process signals involvement of more critical structures of the orbit and the possibility of extension into the cavernous sinus and intracranial structures.

Soft Tissue Anatomy There are seven extraocular muscles: the superior, inferior, medial and lateral rectus; the superior and inferior oblique; and the levator palpebrae superioris muscles. The levator palpebrae muscle can be seen immediately above the superior rectus muscle. With the exception of the inferior oblique muscle, all extraocular muscles originate from the annulus of Zinn, a tendinous ring in the orbital apex. They pass anteriorly and insert on the globe just behind the corneoscleral border. The four rectus muscles and the ibrous septa connecting between them form the muscle cone of the orbit. The intraconal space is illed with orbital fat. Orbital vessels, sensory and motor nerves to the extraconal muscles, and the optic nerve–sheath complex also traverse the intraconal space. The optic nerve may appear straight or slightly tortuous depending on the eye position. It consists of three segments: orbital, canalicular, and intracranial. The orbital segment is covered by the same meningeal sheaths as the brain. The normal diameter of the optic nerve is up to 4 mm. A layer of cerebrospinal luid can be seen between the meningeal sheath and optic nerve. The extraconal space represents the area between the muscle cone and bony orbit. This space contains orbital fat and the lacrimal gland. The lacrimal gland is located superolateral to the globe. The upper margin of the gland is convex. The lower margin is concave and lies on the levator palpebrae and lateral rectus muscles. The lacrimal system drains through the lacrimal ductal system near the medial canthus. It consists of the superior and inferior puncta, their associated

CHAPTER 20 c

d

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Orbit e

f

g

b e b

f a

j h

a

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g

Frontal bone

Frontozygomatic suture

Lamina papyracea Zygomatic bone

C

Maxillary bone

Infraorbital foramen Superior orbital fissure

D

Optic canal

Inferior orbital fissure

Anterior clinoid process

Optic strut

FIG 20-1 A, Coronal CT scan: normal anatomy. Lateral rectus (a), superior rectus (b), medial rectus (c), superior oblique (d), levator palpebrae superioris (e), lacrimal gland (f), inferior oblique (g). B, Medial rectus (a), superior oblique (b), ophthalmic artery (c), superior rectus/levator palpebrae superioris complex (d), dural sheath (e), superior ophthalmic vein (f), subarachnoid space (g), optic nerve (h), inferior rectus (i), lateral rectus (j). C, Bony orbits at midanterior level. D, Bony orbits at orbital apex.

ducts, the lacrimal sac, lacrimal duct, and the valve of Hasner, which is a draining oriice inferolateral to the inferior nasal turbinate. The vascular anatomy of the orbits can be well demonstrated on high-resolution MRI16 and CT angiography (CTA). The primary arterial supply to the orbit is the ophthalmic artery. It is superior to the optic nerve and can be seen crossing the optic nerve almost perpendicularly (Fig. 20-4). The ophthalmic artery most often originates from the internal carotid artery. The origin is usually at the anteromedial aspect of the internal carotid artery as it exits the cavernous sinus. Variants of its origin include the cavernous segment of the internal carotid artery and the middle meningeal artery (i.e., external carotid artery branch). Secondary arterial supply to the orbits comes from the external carotid artery. Because the orbits receive blood supply from both the internal and external carotid arteries, orbital arteries may serve as anastomoses between the two arterial systems. The largest orbital vein visualized on CT or MRI is the superior ophthalmic vein. It can be seen arising near the base of the nose, coursing anteromedially to posterolaterally, and draining into the cavernous

sinus. It crosses over the optic nerve in its midcourse at approximately 20 degrees (see Fig. 20-4). The midportion of the superior ophthalmic vein is an intraconal structure that lies between the superior rectus muscle and the ophthalmic artery. The inferior ophthalmic vein is much smaller than the superior ophthalmic vein. It is usually not well visualized on CT or MRI studies. Both the superior ophthalmic vein and inferior ophthalmic vein receive tributaries from the veins of the face and nose.

IMAGING TECHNIQUES The major modalities for imaging the orbits include CT and MRI. The abundance of intraorbital fat provides good intrinsic soft tissue contrast on CT for most clinical applications. The advances of multidetector CT technology now make high-resolution CT imaging possible. The source images can be reformatted in different planes, providing high-resolution isotropic imaging. This renders the previous advantage of multiplanar capability of MRI obsolete. CT is superior to MRI

588

PART II CT and MR Imaging of the Whole Body Lacrimal sac and duct

Inferior rectus m.

Inferior orbital fissure

A Ciliary bodies

Medial rectus m.

Anterior chamber Lens Vitreous cavity Lateral rectus m. Optic nerve and sheath

B

Ophthalmic artery Lacrimal gland

C

Lacrimal vein

Superior orbital fissure Superior orbital fissure

Superior ophthalmic vein

FIG 20-2 Normal orbital anatomy. Direct axial CT scanning from inferior to superior. A to D, Soft tissue window.

CHAPTER 20 Superior oblique m.

D

Trochlear m.

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589

Orbital septum

Superior rectus m. Lacrimal gland Nasomaxillary Lamina suture papyracea

Zygomatic bone

Sphenozygomatic suture Greater wing of sphenoid Sphenotemporal suture

E

Superior orbital fissure

Optic canal

Optic strut

FIG 20-2, cont’d E, Bone window.

Major Foramina of the Orbit and Their Neurovascular Contents BOX 20-1 Optic Canal Optic nerve Ophthalmic artery Superior Orbital Fissure Cranial nerves: III, IV, VI, V1 Lacrimal and frontal nerves Superior and inferior ophthalmic veins Inferior Orbital Fissure Cranial nerve: V2 Zygomatic nerve Infraorbital vessels

for delineation of osseous structures and calciications. It requires short imaging time and is therefore less sensitive to motion of the globe and eyelid. CT imaging can be completed quickly and requires less patient cooperation, making it ideal for imaging orbital trauma. Compared to CT, MRI provides superior soft tissue contrast. It also provides better imaging details of the intracranial structures. When it is important to assess intracranial abnormalities, either as direct

extension of orbital lesions or as associated lesions in certain diseases (e.g., in multiple sclerosis), MRI is superior to CT. In the past, evaluation of suspected vascular lesions of the orbits required conventional angiography. The advances in CTA and MRA now allow many vascular lesions to be evaluated noninvasively. In some cases, conventional angiography can be foregone. CT and MRI often provide complementary roles in orbital imaging. The choice of CT versus MRI for initial imaging of the orbits depends on the clinical problem. CT is usually preferred for trauma, for evaluation of the bony orbits or calciied lesions, and when MRI is contraindicated. For other applications, MRI is generally preferred because of the absence of radiation risks and its high soft tissue contrast. MRI is the initial imaging of choice for evaluation of the optic nerve, other cranial nerves, and intracranial lesions. Exceptions can be found in a small number of optic nerve meningiomas, which are very small and mostly calciied. These lesions may be missed by MRI and are better detected by CT.

Computed Tomography The orbits are often included in routine CT head or maxillofacial CT examinations. These screening examinations are usually performed according to the standard head or maxillofacial CT protocols. When dedicated orbital CT is performed, thin sections (usually < 3 mm and preferably < 1.5 mm) are acquired. Coronal images are especially important in that cross-sectional evaluation of all of the

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PART II CT and MR Imaging of the Whole Body Cornea

Horizontal section Zonular fibers (suspensory ligament of lens) Scleral venous sinus (canal of Schlemm)

Capsule of lens Lens Iris

Scleral spur

Anterior chamber Posterior chamber Iridocorneal angle Ciliary processes

Ciliary body and ciliary muscle Bulbar conjunctiva Ciliary part of retina Ora serrata

Tendon of lateral rectus muscle

Tendon of medial rectus muscle

Optic (visual) part of retina Vitreous body

Choroid

Hyaloid canal

Perichoroidal space Sclera

Lamina cribrosa of sclera

Fascial sheath of eyeball (Tenon’s capsule)

Optic nerve (II)

Episcleral space Fovea centralis in macula (lutea)

Central retinal artery and vein

Outer sheath of optic nerve Subarachnoid space

FIG 20-3 Illustration of the globe showing the structures of the anterior and posterior segments. The anterior segment is divided into anterior and posterior chambers. (From Netter FH: Atlas of human anatomy, ed 4. St. Louis, 2006, Elsevier, p 87. Netterimages.com Image ID 4627. ©2006 Elsevier Inc. All rights reserved. www.netterimages.com.)

CHAPTER 20

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b a

a a

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C FIG 20-4 CTA of the orbits, superior to inferior (A to C). The ophthalmic artery (a) arises from the internal carotid artery as it exits the cavernous sinus. It enters the orbit through the optic canal and crosses the optic nerve underneath the superior rectus muscle. The superior ophthalmic veins (b) cross the optic nerve more distally and at a more obtuse angle.

intraorbital structures is optimal (e.g., extraocular muscles, optic nerve–sheath–nasal complex, vessels, and globe) (see Fig. 20-1). This plane is also imperative for assessing spread of processes from surrounding structures (e.g., paranasal sinuses, trauma, tumor). A typical orbital CT protocol can be performed with scanning in the axial plane. This plane is usually chosen to be parallel to the orbital long axis. In practice, imaging is performed in the plane parallel to the infraorbitalmeatal line. Coronal images should be included in the routine protocol and can be obtained by multiplanar reformation. This can be performed in the plane perpendicular to the axial plane. Parasagittal reformation in a plane parallel to the long axis of the optic nerve may also be added. Intravenous contrast is often used in the evaluation of inlammatory, infectious, neoplastic, and vascular orbital diseases. For evaluation of vascular lesions, a bolus injection may be used for better depiction of its arterial blood supply. When orbital varix is suspected, the CT study should be repeated without and with the Valsalva maneuver. Enlargement of a lesion with the Valsalva maneuver is indicative of an orbital varix. Less commonly, cavernous hemangiomas may enlarge with the Valsalva maneuver.18 In

patients unable to cooperate, similar effects can be obtained by positioning the patient prone during scanning. CTA can provide good depiction of the major vascular anatomy in the orbits. In addition to the ophthalmic artery and superior ophthalmic vein, their branches, tributaries, and many other smaller vessels can often be seen and traced. The study can be performed as part of a CT angiographic study of the head and neck (see Fig. 20-4).70 Bolus injection of iodinated contrast is required. It is important to use a ield of view suficiently wide to include extraocular pathology that may be associated with the vascular orbital lesions, such as carotid-cavernous istula. CT dacryocystograms can be performed by administration of contrast material into the nasolacrimal duct to evaluate for patency1 (Fig. 20-5). This requires cannulation of the lacrimal duct, usually by an ophthalmologist.

Magnetic Resonance Imaging MRI of the orbits can be performed with the head coil. For highspatial-resolution imaging of the anterior orbital structures, special orbital surface coils may be advantageous. However, the sensitivity of

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PART II CT and MR Imaging of the Whole Body

A

B FIG 20-5 A, Coronal reformatted image from a CT dacryocystogram shows dilation of the lacrimal duct (arrow). The nasal septum and inferior turbinate are deviated leftward and cause obstruction at the valve of Hasner. B, The obstruction is only partial, as evidenced by the presence of contrast material in the posterior nasopharynx (arrow). a f e

d

b

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A d e

f g

c b

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C FIG 20-6 A, Coronal T1-weighted MRI study: normal anatomy. Superior ophthalmic vein (a), lateral rectus (b), inferior rectus (c), medial rectus (d), superior oblique (e), superior rectus-levator palpebrae superioris complex (f). B, Axial T1-weighted MRI study: normal anatomy. Optic nerve in the optic canal (a), optic nerve sheath complex (b), medial rectus (c), anterior chamber (d), lens (e), lid (f), medial and lateral aspects of the orbital septum (arrow; g), lateral rectus (h). C, Axial T2-weighted MRI study: posterior visual apparatus. Position of lateral geniculate body (arrows), path of optic radiations (arrowheads).

surface coils decreases rapidly with distance from the coils, leading to rapid signal falloff and inadequate coverage of deeper structures. For routine imaging, the ield of view should include the cavernous sinus, optic chiasm, optic tracts and radiations, and the nuclei of the oculomotor, abducens, and trochlear nerves in the midbrain and pons. The protocol should include T1- and T2-weighted imaging in axial and coronal planes (Fig. 20-6). Intravenous gadolinium (Gd) contrast

is routinely used. For dedicated orbital imaging, fat suppression is usually performed for T2-weighted imaging and post-Gd imaging to prevent obscuration of enhancing lesions by the high intraorbital fat signal (Figs. 20-7 and 20-8). Fat suppression is often performed with standard frequency selective presaturation radiofrequency (RF) pulses. Alternative advanced fat-suppression techniques can provide more robust fat suppression in

CHAPTER 20 adverse conditions when magnetic ield inhomogeneity is encountered. These techniques may be based on specialized RF pulses (e.g., adiabatic pulses) or modiications of the Dixon technique (e.g., iterative decomposition of water and fat with echo asymmetry and the least-squares estimation [IDEAL]).14 The fat suppression for luidsensitive imaging (i.e., T2-weighting) can also be performed effectively using inversion recovery32 (Fig. 20-9). Orbital MRI is susceptible to image artifacts because of several factors.27 First, chemical shift artifacts may be seen at the interface of the orbital fat and the globe. Similar artifacts may also be present if silicone oil is used to ill the globe in treatment of retinal detachment. These chemical shift artifacts can be reduced by using fat or silicone saturation, using a higher gradient strength, or narrowing the bandwidth. Second, the proximity of orbital structures to the air cavities of

a

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paranasal sinuses makes orbital imaging susceptible to image artifacts. Exogenous metallic materials (e.g., cosmetics) can also lead to susceptibility artifacts. Third, motion artifacts may be present. To minimize motion of the globe, a patient can be asked to ixate his or her vision at a certain object when the eyes are open. Temporal averaging can also be performed. MR dacrocystography can be performed in a similar fashion as CT dacrocystography, by cannulation and instillation of Gd contrast material into the nasolacrimal duct.46 It has comparable sensitivity to CT dacrocystography.46

APPROACH TO DIFFERENTIAL DIAGNOSIS A large number of disease processes can involve the orbits, and orbital complaints such as proptosis, orbital pain, visual loss, and ophthalmoplegia are nonspeciic. Proptosis is abnormal protrusion of the globe; exophthalmos is abnormal prominence of the globe. On imaging, proptosis is best evaluated at a level of the lens on axial images. A line connecting the most distal tips of the lateral orbital walls is drawn. The distance from the anterior margin of the globe to this line should not exceed 21 mm.30

c

h

General Principle d

g e f

FIG 20-7 Coronal post-Gd T1-weighted MRI study with fat saturation: normal anatomy. a, superior rectus/levator palpebrae superioris complex; b, superior ophthalmic vein; c, optic nerve; d, lateral rectus; e, dural sheath; f, inferior rectus; g, medial rectus; h, superior oblique.

A

Orbit

Various characteristics of an orbital lesion can be used to help construct a differential diagnosis. These include its location, anatomic structure, and imaging features and the clinical presentation of the patient.23,36,38,62 Using a compartmental approach a lesion is irst localized to one of the four compartments: globe, optic nerve–sheath complex, intraconal space, or extraconal space. Differential diagnosis of an extraconal lesion can be further reined if it can be determined to be associated with the lacrimal gland and apparatus. Once the primary location of a lesion is determined, other parameters including imaging features (e.g., characteristics of margin, associated bony changes, enhancement patterns), pathophysiologic basis, age of presentation, and chronicity can be considered to further reduce the differential diagnosis. The presence of calciication may also be helpful in reining the differential diagnosis, especially for globe lesions.

B FIG 20-8 A, Precontrast axial T1-weighted image performed without fat suppression demonstrates a mass at the left orbital apex in a patient with known cutaneous lymphoma. B, Postcontrast T1-weighted image of the same patient in which the fat-saturation pulse failed to suppress the orbital fat (this may be due to dental artifact). The lesion demonstrates marked contrast enhancement and is now indistinguishable from the high signal of the orbital fat. This case illustrates the importance of performing nonsuppressed precontrast images and fat-suppressed postcontrast studies.

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PART II CT and MR Imaging of the Whole Body Differential Diagnosis of Globe Lesions23,36 BOX 20-2

Congenital Persistent hyperplastic primary vitreous Coats’ disease Coloboma Globe hypoplasia/aplasia

b

a

c

Degenerative Optic nerve drusen Phthisis bulbi Staphyloma Trauma Vitreous hemorrhage Choroidal hematoma Choroidal effusion Foreign body Inlammatory Orbital pseudotumor (uveal/scleral thickening) Sclerosing endophthalmitis (Toxocara canis)

FIG 20-9 Coronal inversion recovery fast-spin echo MRI study: normal anatomy. a, optic nerve; b, subarachnoid space with cerebrospinal luid; c, optic nerve sheath.

Obviously some lesions may extend over more than one compartment. Nevertheless this compartmental approach helps simplify the diagnostic thought process. The optic nerve–sheath complex, strictly speaking, is also an intraconal structure. However, because of its unique signiicance, it can be considered a separate compartment to improve the speciicity of the differential diagnosis. Differential diagnosis of orbital lesions is summarized in Boxes 20-2 to 20-7. Apart from aiding differential diagnosis, localization of a lesion in the extraconal space versus the intraconal space may also have management implications. In general, intraconal lesions may require surgical attention, whereas extraconal lesions may be amenable to medical management.

Speciic Clinical Scenarios It may be helpful to give a few clinical scenarios their own differential consideration. The irst is lesions of the lacrimal gland and apparatus.1 Lacrimal lesions are most often benign inlammatory processes, with tumors being less common.69 Viral adenitis is the most common acute process. More chronic inlammatory processes include sarcoidosis, Wegener’s granulomatosis, and Sjögren’s syndrome. Histologically the lacrimal gland is analogous to the minor salivary gland in other regions of the head and neck. They therefore share many common pathologic processes. Most lacrimal gland tumors are epithelial cell tumors, with half of these being benign mixed tumors and half carcinomas. Lymphoma also occurs commonly at the lacrimal gland fossa (see further discussion under “Lacrimal Gland and Apparatus”). In a young patient presenting with leukokoria, one will need to exclude retinoblastoma. Other differential considerations include developmental and congenital conditions such as retinopathy of prematurity, Coats’ disease, persistent hyperplastic primary vitreous, toxocariasis, retina dysplasia, and congenital retinal fold.

Neoplasm Uveal melanoma (adults) Retinoblastoma (children) Metastasis Choroidal hemangioma Medulloepithelioma

Differential Diagnosis of Globe Lesions Associated with Calciication23,36 BOX 20-3

Congenital Degenerative Cataracts Optic nerve drusen Phthisis bulbi Retinal detachment (chronic) Retrolental ibroplasia Calciication of ciliary muscle insertion Iatrogenic (e.g., scleral banding) Trauma Foreign body Inlammatory Infection (cytomegalovirus, herpes simplex, rubella, syphilis, toxoplasmosis, tuberculosis) Neoplasm Astrocytic hamartoma (neuroibromatosis, tuberous sclerosis, von HippelLindau syndrome) Retinoblastoma (children) Choroidal osteoma Metabolic Hypercalcemia Sarcoidosis

CHAPTER 20 BOX 20-4

Differential Diagnosis of Optic Nerve Sheath Lesions23,36

BOX 20-5

Trauma Contusion Hematoma Optic nerve avulsion

Trauma Hematoma Foreign body

Infection Toxoplasmosis Tuberculosis Syphilis Noninfectious Inlammatory Thyroid ophthalmopathy Optic neuritis Pseudotumor Sarcoidosis Vascular Central retinal vein occlusion Neoplasm Optic nerve glioma Meningioma Neuroibroma Schwannoma Lymphoma/leukemia Metastasis Hemangioblastoma Hemangiopericytoma Miscellaneous Increased intracranial pressure Optic hydrops

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Differential Diagnosis of Conal/ Intraconal Lesions23,36

Infection Cellulitis Abscess Noninfectious Inlammatory Thyroid ophthalmopathy Pseudotumor Sarcoidosis Wegener’s granulomatosis Vascular Carotid-cavernous istula Venous varix Superior ophthalmic vein thrombosis Venous angioma Arteriovenous malformation Cavernous hemangioma (adults) Capillary hemangioma (children) Lymphangioma Neoplasm Lymphoma Metastasis Rhabdomyosarcoma (children) Hemangiopericytoma Neuroibroma/schwannoma (cranial nerve III, IV, VI) Ectopic meningioma

Orbital diseases can be categorized based on their pathophysiology: trauma, infection, noninfectious inlammation, neoplasm, vascular lesions, congenital and developmental abnormalities, and degenerative conditions. A more popular approach for differential diagnosis is based on a compartmental approach (see earlier).

Evaluation for foreign bodies is best performed with thin-section CT (Fig. 20-11). Wood fragments pose a challenge to CT evaluation because they may have variable densities owing to differences in hydration. Wood may appear hypodense, isodense, or hyperdense. Air may be present within a wood fragment.59 Therefore unusual air pockets should be evaluated carefully. In certain situations, wooden and organic foreign bodies may be better evaluated with MRI.39

Trauma

Infection

CT is the imaging method of choice for evaluation of orbital trauma. The most common traumatic injury is fracture of the orbital walls. Less commonly, hemorrhage in the globe, globe rupture, perforation and penetrating injury, and contusion or avulsion of the optic nerve sheath may occur. A common type of orbital fracture is “blowout” fracture, which results from increased intraorbital pressure transmitted to the orbital walls secondary to blunt trauma (Fig. 20-10). Blowout fractures most often involve the inferior and medial walls because they are the thinnest. Inferior blowout fracture commonly involves the infraorbital foramen, which is the weakest point of the orbital loor. Intraorbital soft tissue contents may herniate through the fracture. Muscle entrapment is a potential complication of orbital fractures. Because the extraocular muscles are tethered to the orbital walls by tiny ibrous strands that are too small to image on CT or MRI, muscle entrapment may occur even without herniation of the muscle itself.37

Orbital infection is most often caused by direct extension from adjacent structures; hematogenous infection is less common. It is important to localize orbital infection to the following compartments: (1) preseptal versus postseptal and (2) extraconal versus intraconal. Preseptal or extraconal infection can usually be treated by standard antimicrobial therapy. Postseptal or intraconal infection requires more aggressive management because of the risk of neurovascular injury and further intracranial spread.22 Identiication of orbital abscesses is also crucial because they may require surgical intervention. Orbital infection is most commonly caused by contiguous spread of sinusitis or a supericial periorbital cellulitis of the face. In children, infection is most commonly secondary to extension from ethmoid air cells (Fig. 20-12), whereas in adults, extension from the frontal sinus is most common67 (Fig. 20-13). Common organisms include Streptococcus pneumoniae and β-hemolytic streptococci. Haemophilus inluenzae, staphylococci, and anaerobes are less common.

PATHOPHYSIOLOGY

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PART II CT and MR Imaging of the Whole Body

BOX 20-6

Differential Diagnosis of Extraconal Lesions23,36

BOX 20-7

Differential Diagnosis of Lacrimal Gland and Apparatus Lesions1,23,36

Trauma Fracture Hematoma Infection Cellulitis Abscess

Trauma Hematoma Infection Dacryoadenitis Noninfectious Inlammatory Pseudotumor Postviral syndrome Sarcoidosis Sjögren’s syndrome Mikulicz’s syndrome Wegener’s granulomatosis

Noninfectious Inlammatory Pseudotumor Postviral syndrome (lacrimal gland) Sjögren’s syndrome (lacrimal gland) Mikulicz’s syndrome (lacrimal gland) Neoplasm Metastasis Primary malignancy from adjacent structures Benign mixed tumor (lacrimal gland) Adenoid cystic carcinoma (lacrimal gland) Non-Hodgkin’s lymphoma Rhabdomyosarcoma (children)

Neoplasm Papilloma Benign mixed tumor (pleomorphic adenoma) Adenoid cystic carcinoma Mucoepidermoid carcinoma Adenocarcinoma Malignant mixed tumor Undifferentiated carcinoma Squamous cell carcinoma Sebaceous carcinoma Primary malignancy from adjacent structures Non-Hodgkin’s lymphoma Metastasis Dermoid/epidermoid

Congenital Cephalocele Dermoid/epidermoid

Congenital Dacryocele Dacryocystocele

m

m

FIG 20-11 CT scan shows intraconal metallic foreign bodies just FIG 20-10 CT scan shows blowout fracture of the left orbital loor with herniation of extraconal fat and inferior rectus muscle (arrow). m, maxillary sinus.

medial to the medial rectus (large arrow) and intraocular (small arrow). Scleral band in place in right globe (arrowheads).

CHAPTER 20 CT is the imaging modality of choice because it can demonstrate inlammatory soft tissue changes, luid collections/abscesses, and bone changes (e.g., osteomyelitis). Imaging indings vary from mild mucoperiosteal thickening or elevation to frank intraorbital abscesses.

Inlammation Thyroid-Associated Ophthalmopathy. Thyroid-associated ophthalmopathy is an autoimmune-mediated inlammation of the extra-

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ocular muscles and periorbital connective tissues. It is most often associated with Graves’ disease, although association with other thyroid diseases such as Hashimoto’s thyroiditis, thyroid carcinoma, and neck irradiation has also been reported. In approximately 10% to 20% of patients, thyroid-associated ophthalmopathy may present before any other clinical symptoms or signs. Clinical presentation may include eyelid retraction, proptosis, chemosis, periorbital edema, and impaired ocular motility. The classic imaging indings are fusiform enlargement of the extraocular muscles with sparing of the tendinous attachments (which may be dificult to appreciate when muscle enlargement is severe), and inlammatory changes of the periorbital fat (Fig. 20-14). There may be increase of intraorbital fat. The lacrimal glands may also be affected. The extraocular muscles most often affected, in descending order of frequency, are the inferior rectus, medial rectus, and superior rectus– levator palpebrae muscle complex.52 Periorbital soft tissue swelling and proptosis may be seen. Involvement is usually bilateral but may be asymmetric. Direct involvement of the globe and optic nerve sheath is uncommon. However, secondary compression of the optic nerve sheath may occur and can lead to irreversible visual loss. It is important to assess for this possibility on imaging.

FIG 20-12 CT scan shows an extraconal subperiosteal abscess (small

Orbital Pseudotumor. Orbital pseudotumor is also known as idio-

arrowheads). This is a complication of ethmoid sinusitis. A thickened displaced medial rectus (large arrowhead) and preseptal soft tissue swelling (arrows) are seen.

pathic orbital inlammatory disease. It is an idiopathic nongranulomatous inlammatory process that often involves the extraocular muscles and orbital fat. Less frequently, other intraorbital structures including the uveal tract, sclera, optic nerve, and lacrimal glands may be involved.13,17,47,48 Involvement of these structures can occur in isolation without extraocular muscle involvement. Tolosa-Hunt represents a variant form of pseudotumor that involves the cavernous sinus. When muscular involvement is present, it is usually diffuse. As opposed to thyroid-associated ophthalmopathy, involvement is often unilateral and there is usually extension to the muscular tendon attachments (Figs. 20-15 and 20-16). Orbital pseudotumor is usually painful, which helps distinguish it from thyroid-associated ophthalmopathy. Orbital pseudotumor may be dificult to differentiate from other tumefactive inlammatory processes and neoplasms. A quick response to a trial steroid therapy may help establish the diagnosis.49 Alternative diagnosis needs to be excluded when there is poor response to therapy or recurrence.

Sarcoidosis. Sarcoidosis is a noninfectious granulomatous disease FIG 20-13 CT scan shows subperiosteal abscess of the superior orbit (arrowheads) from ethmoid or frontal sinus disease.

A

that may affect any part of the optic pathway from the globe to the optic radiations.9 The lacrimal gland, anterior layer of the globe, and

B FIG 20-14 A, Axial contrast-enhanced CT scan shows Graves’ ophthalmopathy characterized by enlarged superior, medial, and inferior recti with compromise of the orbital apex. Note the sparing of the muscle tendon insertions. B, Coronal contrast-enhanced CT scan in the same patient.

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PART II CT and MR Imaging of the Whole Body

A

B FIG 20-15 A, Axial CT scan shows pseudotumor of the orbit with swollen bilateral medial rectus (arrows), which includes tendinous insertion on the globe. Thickening and enhancement of the globe (arrowheads) are also shown. B, Coronal CT scan shows pseudotumor of the orbit in the same patient.

FIG 20-16 CT scan of orbital pseudotumor with bilateral medial rectus and left lacrimal involvement.

FIG 20-18 Axial T1-weighted MRI study with Gd shows sarcoid of the chiasm (long arrow), left cerebral peduncle (large arrowhead), lateral geniculate body (short arrow), and superior colliculus (small arrowhead).

On MRI, retrobulbar masses may demonstrate marked hypointensity. Although this inding is not unique, it strongly suggests Wegener’s granulomatosis.12,56

Optic Neuritis. Optic neuritis represents nonspeciic inlammation FIG 20-17 Axial T1-weighted MRI study with Gd shows sarcoid of the anterior left globe (arrowheads).

eyelids are commonly involved. The imaging indings can simulate pseudotumor (Figs. 20-17 and 20-18).

Wegener’s Granulomatosis. This is a form of necrotizing granulomatous vasculitis. Orbital involvement is common and seen in slightly more than 50% of patients.25,31,51 Any orbital structures can be involved. Findings may include conjunctivitis, episcleritis, scleritis, uveitis, optic nerve vasculitis, retinal artery occlusion, nasolacrimal duct obstruction, and retrobulbar diseases. CT examination may demonstrate nonspeciic nodules or iniltrates in the retrobulbar space.56,66 Enhancement is generally present.

of the optic nerve that can be associated with infection, granulomatous diseases, pseudotumor, postradiation, or demyelinating diseases. A large proportion of cases are idiopathic. Association with multiple sclerosis is established in approximately 50% of patients.3 Imaging indings are best demonstrated on MRI, which may include enhancement and T2 prolongation (Fig. 20-19). These indings can be subtle. It is important to include the whole brain in image evaluation to exclude intracranial lesions, particularly the presence of demyelinating lesions.

Neoplasms Lymphoma. Lymphoma is the most common neoplasm in the orbit, accounting for just over half of all cases.69 B-cell lymphomas of the non-Hodgkin’s type are by far the most common, although T-cell lineages have also been described.11 Usually orbital lymphomas are

CHAPTER 20 primary to the orbit, but occasionally orbital manifestation of a systemic lymphoproliferative process is seen. The usual appearance is a well-deined mass within the muscle cone (Figs. 20-20 and 20-21; see Fig. 20-8). Less frequently, extraconal masses or diffuse iniltration of the orbital fat can be seen. The differential diagnosis includes pseudotumor and metastasis. Lacrimal gland involvement can be seen either in isolation or in

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combination with the other manifestations of lymphoma within the orbit.

Optic Glioma. Optic gliomas most often occur in children, especially between the ages of 2 and 6 years. They are usually benign, but a small number of lesions may develop aggressive behavior.73 This lesion usually involves the anterior optic apparatus (e.g., optic nerves, chiasm, and optic tracts) and causes enlargement and often tortuosity of these structures. About half of all optic gliomas occur in patients with neuroibromatosis type 1, and 10% to 15% of neuroibromatosis type 1 patients develop optic gliomas15 (Fig. 20-22). These lesions do not calcify.8 MRI has become the modality of choice, given the necessity of evaluating the intracranial extent of the tumor (Fig. 20-23). Optic gliomas are typically either nonenhancing or weakly enhancing. The lesions are generally isointense to slightly hypointense on T1-weighted images and hyperintense on T2-weighted images.21 CT can help in assessing bony changes and is especially valuable in detecting expansion of the optic canal. CT thus complements MRI in evaluation of these lesions.

Optic Nerve Sheath Meningioma. Optic nerve sheath meningioFIG 20-19 Coronal MRI study, inversion recovery fast-spin echo, shows left optic neuritis. Contrast the increased signal at the left optic nerve (long arrow) with the low signal of the normal right optic nerve (short arrow).

A

mas (ONSMs) are meningiomas that arise from the meninges surrounding the optic nerve. It is not an uncommon tumor, making up between 5% and 7% of primary orbital tumors.33 The onset occurs at a median age of 38 years and is seen four times more frequently in

B

FIG 20-20 A, T1-weighted axial MRI study shows a large mass

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replacing the intraconal fat in the right orbit (arrow). B, T2-weighted axial image of the same patient. C, Gd-enhanced axial T1-weighted image of the same patient demonstrates marked enhancement (black arrow). Fat suppression allows the smaller lesion to be visible at the apex of the left orbit (white arrow).

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M M M M

C FIG 20-21 Orbital lymphoma. A, Contrast-enhanced CT scan demonstrates a homogeneously enhancing intraconal mass (black arrow) adjacent to the left optic nerve, causing medial deviation of the nerve (white arrow). B, Axial post-Gd fat-suppressed T1-weighted image conirms the CT indings (long arrow shows the enhancing mass; short arrows show the optic nerve). C, Coronal post-Gd fat-suppressed images more clearly demonstrate the enhancing mass (long arrow) separate from the nonenhancing left optic nerve (short arrow). M, extraocular muscles.

FIG 20-22 Axial T1-weighted MRI study shows optic glioma of bilateral optic nerves, with involvement of the chiasm (arrows) in a patient with neuroibromatosis.

females than males.33 Because meningiomas in general occur more frequently in patients with neuroibromatosis type 2, ONSM also occurs more frequently in these patients. The presenting symptom with ONSM is usually diminished visual acuity from optic nerve compression or proptosis. If there is no evidence of visual loss or intracra-

nial extension, these lesions are often treated by close observation. In the setting of visual loss, radiation treatment is frequently used. Surgery is usually reserved for intracranial extension and larger tumors. On axial imaging, the most common presentation is the wellknown tram track appearance caused by the enhancing tumor wrapping around the sheath (Fig. 20-24). Inlammation of the dura from other causes may occasionally have a similar appearance. ONSM can also present a fusiform enlargement of the sheath on one side (Fig. 20-25). As with all meningiomas, they enhance vividly with contrast and often demonstrate calciication. Hyperostosis may occasionally be seen when the lesion is at the orbital apex or in the optic canal. Optic nerve glioma may initially have the appearance of a meningioma on the axial images, but on the coronal fat-suppressed enhanced MRI, the nerve should be seen separate from the surrounding enhancing meningioma. Although MRI is the imaging modality of choice, thin-section CT is often helpful because it demonstrates the calciications or hyperostosis that may be present, thus aiding in the differential diagnosis. A noncontrast CT scan should be performed irst so that the enhancing tumor does not hide the calciications. ONSMs, particularly when in the optic canal, can be quite small and yet cause signiicant symptoms. As a result they can be easily missed unless there is a high degree of suspicion and careful inspection. MRI can therefore be extremely useful for inding these lesions. Coronal and axial contrast-enhanced MRI with fat suppression allows the enhancing lesion to be seen against the fat and bone, which turn dark.

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B FIG 20-23 A, T1-weighted axial MRI study with Gd enhancement shows optic glioma of the optic chiasm (arrows). B, T1-weighted coronal MRI study with Gd.

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B FIG 20-24 A, Coronal contrast-enhanced CT scan shows optic nerve sheath meningioma (arrow). B, Axial contrast-enhanced CT scan shows same patient with “tram track” appearance (arrow).

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FIG 20-25 Axial contrast-enhanced CT scan shows optic nerve sheath meningioma (m). g, globe; arrow, displaced optic nerve sheath complex emerging from mass.

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FIG 20-26 Coronal contrast-enhanced CT scan shows melanoma of the left ciliary body.

Melanoma. Primary orbital melanoma usually presents as an ocular lesion. It originates in the uveal tract (iris, choroid, and ciliary bodies) and may extend posteriorly to the rest of the orbit. On CT imaging, melanomas appear as focal soft tissue masses with mild to moderate enhancement45 (Fig. 20-26). MRI studies may help differentiate melanomas from other ocular lesions, evaluate their intraorbital extent, and search for metastatic disease.55 On MRI studies the amount of melanin contained in melanoma determines the signal characteristics. Melanin shortens T1 and T2, thereby causing increased signal on T1-weighted images and mildly decreased signal on T2-weighted images (Fig. 20-27). MR signal is also affected by hemorrhage, which is not uncommon in patients with melanotic lesions. With hemorrhage the differential diagnosis includes retinal and choroidal detachment from other causes (Fig. 20-28). The presence of Gd enhancement favors melanomas and helps differentiate the tumor from retinal detachment.6,44 Although melanotic lesions have characteristic appearances, nonpigmented melanomas cannot be reliably differentiated from other masses.58 Metastatic Disease. In adults the most common tumor to metastasize to the orbit is breast carcinoma. Other primary sites include lung, colon, and prostate (Fig. 20-29). In children the most common primary lesions include neuroblastoma, leukemia, and Ewing’s sarcoma. Metastatic lesions may affect any of the intraorbital structures as well as the bony orbit itself29,64 (Fig. 20-30). None of the available imaging techniques offers speciicity to differentiate metastases from the many other orbital lesions. The indings may be subtle, with small areas of focal thickening of the globe, or large destructive lesions.23 In addition, extension of tumor from an adjacent structure (e.g., paranasal sinuses) may occur (Fig. 20-31). Enophthalmos may be present in primary disease that is often associated with extensive ibrous response, such as scirrhous carcinoma of the breast.

Retinoblastoma. Retinoblastoma is seen primarily in infants and has an occurrence of 1 in every 18,000 to 30,000 live births.54 It is responsible for 1% of all childhood cancer-related deaths in the United States.63 Early diagnosis extends the 5-year survival rate to more than 90%; however, if the tumor extends beyond the globe, the mortality rate approaches 100%.35 Retinoblastoma has been strongly linked to mutations on the RB1 allele of chromosome 13. Whereas about 10% of cases are said to be inherited, most retinoblastoma cases are not inherited. Hence there is both a familial hereditary form of retinoblastoma and a nonfamilial sporadic form. Aside from the hereditary differences, the tumors are the same. Patients with nonfamilial retino-

FIG 20-27 Ocular melanoma of the inferior aspect of the globe. Top, T1-weighted coronal MRI study. Bottom, T2-weighted coronal MRI study.

blastoma have unilateral solitary tumors, whereas patients with the familial form have a much higher rate of bilateral than unilateral disease. Patients with the familial form of retinoblastoma have a high incidence of nonocular cancers as well. The term “trilateral retinoblastoma” refers to a patient who has bilateral retinoblastomas and a third midline tumor. The midline tumor is histologically the same as the intraocular tumor and may occur in the pineal region, suprasellar region, or fourth ventricle. It is important to remember that the midline tumor may not be seen at the same time as the ocular tumors but may be discovered several years later. Because most of these lesions that arise from the retina are calciied, CT is extremely important in their diagnosis (Fig. 20-32). The lesions will also enhance with intravenous contrast. The tumor may spread in the lymphatics or along the optic nerve to gain intracranial access. If a tumor is discovered in one globe, very close inspection of the other globe is necessary to exclude bilateral disease. On initial evaluation and on follow-up examinations, close inspection of the pineal region, suprasellar region, and fourth ventricle is important to seek out trilateral disease.

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FIG 20-29 Axial contrast-enhanced CT scan shows prostate metastasis to the left orbit roof.

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FIG 20-30 Axial contrast-enhanced CT scan shows bilateral neuroblastoma metastasis.

C FIG 20-28 A, T1-weighted sagittal MRI study shows retinal detachment with hemorrhage. B, T2-weighted axial MRI study of the same patient as in A. C, Coronal CT scan (different patient) shows retinal detachment. (A and B courtesy Guy Wilms, MD, Universitaire Ziekenhuizer, Leuven, Belgium.)

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B FIG 20-31 A, Axial contrast-enhanced CT scan shows extension of squamous cell carcinoma of the maxillary sinus to the orbit. B, Coronal contrast-enhanced CT scan in the same patient.

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FIG 20-32 Axial contrast-enhanced CT scan shows calciied retinoblastoma of the left eye.

FIG 20-33 Rhabdomyosarcoma of the orbit in a young child. CT demonstrates enhancing soft tissue mass (R). There is aggressive bone destruction, with the tumor extending into the ethmoid sinus (arrow).

Because these tumors enhance, MRI with contrast and fat suppression is excellent for identifying the lesion; however, CT is better at identifying the calciication. With bilateral disease the diagnosis is easy, but with a unilateral tumor it may be more dificult. Entities such as Coats’ disease and Toxocara canis infection can be confused with retinoblastoma, but these typically lack contrast enhancement.

Rhabdomyosarcoma. Even though the most common malignant ocular tumors in children are retinoblastomas, the most common malignant orbital tumors in children are rhabdomyosarcomas.10 They may arise primarily or secondarily in the orbits. They are very aggressive tumors and may grow rapidly. On CT imaging, they are seen as enhancing soft tissue masses with associated permeative or lytic bone destruction (Fig. 20-33). On MRI they are hypointense to isointense on T1-weighted images and isointense to hyperintense on T2-weighted images. Enhancement is variable.2

Langerhans Cell Histiocytosis. Langerhans cell histiocytosis is not a true neoplasm but a reticuloendothelial disorder of unknown origin. Like rhabdomyosarcoma, it occurs most often in children. Because its clinical presentation and imaging features are often similar to neoplastic processes, it is often included in the differential consideration of a soft tissue mass. The imaging appearance can simulate rhabdomyosarcoma.10 On CT imaging an isodense to hyperdense soft tissue mass is seen. Enhancement of the lesion and associated lytic bone changes are usually present.2 On MRI study the mass is isointense to hypointense on T1-weighted images and isointense to hyperintense on T2-weighted images.

Teratoma. The teratoma is a rare benign lesion that contains mixed endodermal, mesodermal, and ectodermal elements. It usually calciies. Because the teratoma is usually seen in neonates, knowing a patient’s age can help one decide whether to include this entity in a differential diagnosis26,74 (Fig. 20-34).

Vascular Abnormalities Carotid Cavernous Fistula. Carotid cavernous istula is an abnormal high-low communication between the arterial and venous circulations. This results in transmission of arterial low into the cavernous sinuses, consequently leading to reversal of low in venous structures draining into the cavernous sinus. Two types of carotid cavernous istulas have been described: direct and indirect. The more common type, direct istula, is formed by an abnormal communication between the internal carotid artery and the cavernous sinus. The less common

FIG 20-34 Axial contrast-enhanced CT scan shows calciied teratoma with areas of enhancement.

indirect istula is an abnormal communication between the dural external carotid artery and the cavernous sinus. Common causes of direct carotid cavernous istula include rupture of the cavernous internal carotid artery secondary to either trauma or spontaneous rupture of an aneurysm. CT or MRI indings include proptosis and engorgement of the superior ophthalmic vein and cavernous sinus (Fig. 20-35). The abnormally high low in the cavernous sinus may lead to the appearance of low void on MRI. There is usually enlargement of extraocular muscles due to impaired venous drainage. Imaging abnormalities may be seen bilaterally if intercavernous venous connections are present. On CTA, engorgement of the cavernous sinuses and ophthalmic veins can be seen. The venous engorgement often extends to the branches of the facial veins through their anastomoses with the ophthalmic veins (Fig. 20-36). Indirect carotid cavernous istula can be caused by trauma. The imaging indings are more subtle than those for direct carotid cavernous istula.

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B FIG 20-35 Carotid cavernous istula. A, Coronal T1-weighted MRI study shows marked enlargement of the left superior ophthalmic vein (arrow). B, Lateral digital subtraction angiogram shows istulous communication between branches of the external carotid and the cavernous sinus. m, middle meningeal artery; F, istula; c, cavernous sinus.

FIG 20-36 CTA of posttraumatic carotid cavernous istula. Note the enlarged superior ophthalmic veins (long arrows) and branches of the facial veins in the periorbital and maxillofacial regions (short arrows).

Cavernous hemangiomas are the most common adult orbital mass lesions (Fig. 20-39). They are actually venous malformations rather than true neoplasms. They tend to be well encapsulated with distinct margins and are usually intraconal. On CT imaging, they are often hyperdense. Phleboliths may be present. On MRIs, signal on T1-weighted images are variable, but hyperintensity may be associated with thrombosis. Cavernous hemangiomas are usually hyperintense on T2-weighted images. Intense enhancement is usually seen with both CT and MRI. Capillary hemangiomas are also known as infantile hemangioma, juvenile hemangioma, hypertrophic hemangioma, and hemangioblastoma (Fig. 20-40). Because they represent true vascular neoplasm, previous authors have advocated simply using the term “hemangioma” to refer to these lesions.50 Capillary hemangiomas often are found in infants during the irst year of life. They tend to regress with age. Prominent arterial supply from the external or internal carotid arterial systems usually is seen. On CT and MRI, they present as an intensely enhancing lobulated mass with low intensity to isointensity on T1-weighted images and hyperintensity on T2-weighted images.18

Venous Varix. Venous varix represents abnormal dilatation of

Lymphangioma. Lymphangiomas usually present at an early age,

orbital veins. The superior ophthalmic vein is most often affected. Etiologies include congenital venous malformation or venous wall weakness; it can also occur in association with intraorbital or intracranial arteriovenous malformation. For evaluation of venous varix, CT is best performed with contrast enhancement, repeated without and with the Valsalva maneuver65,72 (Fig. 20-37). The varix is seen as a large tortuous vein or lobulated masslike conluence of small veins. There is strong contrast enhancement, although heterogeneity can be present if thrombosis is present. Venous varix enlarges signiicantly with the Valsalva maneuver, helping differentiate it from other enhancing lesions. CTA can also be used to diagnose and map the anatomic course of an orbital varix71 (Fig. 20-38).

from infancy to the irst decade of life. They are congenital vascular malformations, and the term venous lymphatic vascular malformation has also been used.34,61 The lesions may involve the extraconal compartment, intraconal compartment, or both. Histologically they may contain a variable amount of lymphatic channels, lymphocytic aggregates, dysplastic vascular channels, loose connective tissue, and smooth muscle ibers. Hemorrhage of different stages may be present. The imaging appearance is variable and relects the histologic composition of individual lesions (Figs. 20-41 and 20-42). Most lesions appear poorly deined, multilobulated, and inhomogeneous.20,24 Septations may be present. Enhancement is variable. On CT imaging, phleboliths or dystrophic calciications may be seen occasionally.18 MRI can provide better details of these lesions. On T1- and T2-weighted images, both hyperintensity and hypointensity may be seen.5

Hemangiomas. Hemangiomas can be classiied into two distinct entities: cavernous and capillary.5 They are seen in different age groups; cavernous hemangiomas are seen in young adults, most commonly between the second and fourth decades of life, whereas capillary hemangiomas are seen in young pediatric patients.

Arteriovenous Malformation. Most orbital arteriovenous malformations are extensions of intracranial lesions with drainage into the orbital veins via the cavernous sinus.19 On CT or MRI, multiple

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B FIG 20-37 Axial contrast-enhanced CT scan. Orbital varix both before (A) and during (B) Valsalva maneuver demonstrates increase in size of the lesion. (Courtesy Robert E. Peyster, MD, Hahnemann Hospital, Philadelphia.)

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FIG 20-38 Contiguous axial CTA images of right orbital varix, from superior orbit (A) to inferior orbit (N). A, Superior ophthalmic vein identiied by white arrow. B to F, Small serpentine vein (arrows) arises from inferior margin of superior ophthalmic vein. G to J, This courses medially and inferiorly into larger upper lobe of lesion (white arrows). I to K, Inferior ophthalmic vein (black arrow) courses into dilated venous conluence. L to N, Venous conluence demonstrates blind-ended anterior extending saccular dilation (arrow), representing lower lobe of lesion. M, Contrast level in lower lobe of lesion (arrow) indicates venous stasis. N, Venous conluence drains through superior orbital issure into cavernous sinus (arrow). (From White JH, et al: Diagnosis and anatomic mapping of an orbital varix by computed tomographic angiography. Am J Ophthalmol 140:945–947, 2005.)

tortuous vessels can be seen. The superior ophthalmic vein may also be dilated.

Congenital and Developmental Abnormalities and Anomalies Coloboma. Coloboma is a congenital defect in the globe at the insertion of the optic nerve. It results from incomplete or inadequate fusion of the fetal optic issure and occurs along the inferomedial aspect of the globe and optic nerve.47 The defect can be bilateral. On CT or MRI the affected globe is usually small. The defect can be seen as a cystic outpouching of vitreous at the site of optic nerve attachment to the globe (Fig. 20-43). A retroocular cyst may be associated. It may present as a small cone-shaped defect at the optic disc or as a large retinal cyst.

Retinopathy of Prematurity. Retinopathy of prematurity is also known as retrolental ibroplasia. It is seen in premature infants requiring long-term ventilation support. Prolonged exposure to high oxygen concentration leads to proliferation of the retinal vascular buds. Involvement is usually bilateral but may be asymmetric. On CT imaging, there is increased density in the vitreous bilaterally. Microphthalmia is often seen, but calciication is uncommon except in advanced cases; these two features distinguish retinopathy of prematurity from retinoblastoma.

Persistent Hyperplastic Primary Vitreous. Persistent hyperplastic primary vitreous is caused by hyperplasia of the residual primary vascular vitreous, which usually involutes by the second trimester. This

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FIG 20-39 A, Axial T1-weighted MRI study shows cavernous

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hemangioma of the medial right orbit. B and C, Axial T2-weighted MRI study in the same patient.

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FIG 20-40 Capillary hemangioma. A, Coronal inversion recovery

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fast-spin echo image demonstrates lobulated hyperintense mass occupying both intraconal and extraconal space. Note the dark low voids in the lesion (white arrow) indicating the presence of distinct blood vessels. There is extraorbital extension (black arrow). B, Coronal fat-suppressed post-Gd image demonstrates intense enhancement of the orbital (white arrows) and extraorbital lesions (black arrow). C, Reformatted coronal CTA conirms the presence of small vessels in the enhancing orbital mass (arrow).

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A FIG 20-42 Recurrent lymphangioma in a 34-year-old woman. Reformatted axial image demonstrates lobulated extraconal lesion with an anterior and a posterior component (L). The lesion is heterogeneous with mild wall enhancement. The posterior component is lateral and abutting the medial rectus muscle (arrow). Note the orbital wall is intact, consistent with a nonaggressive slow-growing process.

B

FIG 20-43 Axial CT scan shows left orbit coloboma. Note the cystic outpouching is at the site of optic nerve attachment (arrow), distinguishing this from staphyloma.

C FIG 20-41 Lymphangioma. A lobulated lesion is seen in the medial aspect of extraconal space. A, Coronal T1-weighted image. B, Coronal T2-weighted image. C, Coronal CT image.

condition may present in male infants as unilateral leukokoria. Therefore retinoblastoma is a strong differential consideration. On CT imaging, the globe is small and demonstrates hyperdensity in the vitreous humor. Enhancement is present. A tissue density band may extend from the back of the lens to the posterior inner surface of the globe.

Coats’ Disease. This is a congenital vascular malformation of the retina characterized by multiple telangiectatic vessels. Leakage of serous and lipoproteinaceous exudates from these vessels leads to retinal detachment and central vision loss. On CT imaging, hyperdensity is seen in part or all of the vitreous. Calciication is usually absent, and the lesion is hyperintense on T2-weighted images, distinguishing this entity from retinoblastoma.42 Enhancement is usually seen in the detached leaves of the retina, which may be displaced to the midline by the massive subretinal effusion.41

Microphthalmia. Microphthalmia represents congenital underdevelopment or acquired diminution in the size of the globe. Congenital

associations include coloboma and craniofacial anomalies such as hemifacial microsomia. Acquired etiologies include intrauterine infections such as rubella.

Dermoids/Epidermoids. Dermoid cysts are the most common benign congenital lesion of the orbit. They arise from epithelial rests sequestered in sutures and most often present during the irst decade of life.53 Although they are most commonly located near the frontozygomatic suture and the lacrimal fossa, dermoid cysts can be found anywhere in the orbits. When they rupture they can elicit a severe inlammatory response. Imaging features include cysts with welldeined walls that may or may not enhance (Fig. 20-44). Fat is often seen within the lesions, giving rise to pathognomonic fat-luid levels. Other tissues such as hair or sweat glands may also be present. The lesion may demonstrate hyperintensity on T1-weighted images owing to the presence of fat. Marginal calciication may be present. Epidermoid cysts do not contain fat, sweat glands, or hair. On MRIs they are usually hypointense on T1-weighted images, but they may be hyperintense when hemorrhage or high proteinaceous material is present (Fig. 20-45).

Degenerative Conditions Calciied Ciliary or Extraocular Muscle Insertions. Calciication of the insertions of the ciliary muscles (ciliary bodies) or extraocular

CHAPTER 20 muscles is commonly seen in older adults. This is usually an incidental inding on CT studies (Fig. 20-46).

Phthisis Bulbi. Phthisis bulbi represents the end stage of injury to the globe. This may be secondary to trauma, infection, or inlammatory disease. On imaging, the globe is usually shrunken, atrophic, and misshapen. Heavy calciication is usually present (Fig. 20-47).

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attachment may have any shape or size but is more commonly V-shaped with a small attachment at the optic disc (Fig. 20-49; see Fig. 20-28). Etiologies of retinal and choroidal detachment include trauma, infection, inlammation, and neoplasm. It is important to consider the possibility of these underlying etiologies (e.g., malignancies), which may have dire effects.

Staphyloma. Staphyloma represents focal outpouching of the scleralOptic Drusen. Optic drusen is usually seen in adults. The lesion may present with prominence of the optic disc that can be misinterpreted as papilledema during funduscopic examination (pseudopapilledema).60 Drusen represents a collection of hyaline-like material on the surface of the optic disc. Discrete calciication is usually present,7 making CT an ideal modality for its evaluation57,68 (Fig. 20-48). In 75% of cases there is bilateral involvement.

Retinal and Choroidal Detachment. The three layers of the globe include the posterior hyaloid membrane, sensory retina, and retinal pigment epithelium layers. Posterior hyaloid detachment represents detachment of the posterior hyaloid membrane from the sensory retina, and retinal detachment represents separation of the sensory retina from the retinal pigment epithelium. Separation of the choroid from the sclera is called choroidal detachment. Choroidal detachment may demonstrate lenticular or moundlike abnormalities. Retinal

uveal coats of the globe (Fig. 20-50). As opposed to coloboma, staphyloma defect is located off-center from the optic disc, typically temporal to the disc. It is an acquired defect secondary to weakness and thinning of the scleral-uveal coats. Patients often present with severe axial myopia. Associations include glaucoma, previous inlammatory process, and trauma.

LACRIMAL GLAND AND APPARATUS The unique histology of the lacrimal gland and apparatus gives rise to its own differential consideration. The most common lesions affecting the lacrimal gland are benign inlammatory processes, with tumors being less common.40 Inlammatory, neoplastic, and traumatic processes can affect the lacrimal gland.69 The patient can present with deviation of the globe, proptosis, or conjunctival injection, depending on the extent of the lesion. With the possible exception of traumatic disruption, glandular

FIG 20-44 Fat-suppressed T2-weighted image of dermoid cyst. A small recurrent dermoid cyst presents as a small well-circumscribed heterogeneous lesion at medial aspect of the right orbit (arrow), the second most common location of orbital dermoids.

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FIG 20-46 Calciied ciliary muscle insertion (arrows).

B FIG 20-45 Epidermoid cysts. A, T2-weighted image demonstrates an epidermoid cyst (arrow). Note the homogeneous signal intensity and typical location at frontozygomatic suture. B, Post-Gd image of the cyst (arrow) demonstrates hyperintensity owing to highly proteinaceous material, but no enhancement.

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FIG 20-47 A, Axial CT scan shows bilateral phthisis

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bulbi. B, Axial T1-weighted MRI study of the same patient. C, Axial T2-weighted MRI study of the same patient.

FIG 20-48 Axial CT scan shows optic disc drusen, right optic nerve head calciication, and optic nerve atrophy.

FIG 20-50 T1-weighted MRI shows staphyloma. Note the thinning of the scleral-uveal outpouching (white arrow), which is temporal to the optic disc (black arrow), thus distinguishing it from coloboma (see Fig. 11-43).

FIG 20-49 CT image showing chronic retinal detachment in the left globe (arrow).

enlargement is common to most lesions. Contrast enhancement does not distinguish between inlammation and neoplasia. In the acute setting, viral adenitis accounts for most of the lesions of the lacrimal fossa and tends to affect a younger population. Chronic disease is usually secondary to granulomatous disease (e.g., sarcoid or

Wegener’s) or autoimmune disease (e.g., Sjögren’s syndrome). Orbital pseudotumor may affect the lacrimal gland. Unilateral or bilateral glandular enlargement as well as variability of enhancement may be seen. The chronic entities tend to be more well marginated than the acute inlammatory processes.40 Tumors of the lacrimal gland may be either benign or malignant. Approximately half of lacrimal neoplasms are tumors of epithelial origin with histopathologic types similar to that of the salivary gland. Benign tumors are most commonly pleomorphic adenoma (also known as benign mixed tumor). They may contain small cystic components. As in the salivary glands, pleomorphic adenoma carries a low accumulative risk of malignant transformation into carcinoma ex pleomorphic (5% at 10 years and 20% at 30 years). This should be considered when more aggressive or invasive features are present.18 Adenoid cystic carcinoma is the most common malignant tumor of the lacrimal gland (Fig. 20-51). Mucoepidermoid carcinoma and adenocarcinoma are also seen. Lymphocytic hyperplasia and lymphoma (Fig. 20-52) make up the bulk of additional tumors.28

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FIG 20-51 A, T1-weighted axial MRI study shows adenoid cystic carcinoma (M) in the left lacrimal gland. The lesion demonstrates T1 hypointensity. Note the normal right lacrimal gland (arrow). B, Coronal fat-saturated T1-weighted post-Gd image demonstrates marked homogeneous enhancement of the mass (M). In the absence of invasive features, it is dificult to differentiate this malignant tumor from benign pleomorphic adenoma. C, Invasive features, such as invasion of preseptal soft tissues (arrows), in another patient with adenoid cystic carcinoma suggest a malignant tumor.

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B FIG 20-52 A, Coronal contrast-enhanced CT scan shows left lymphoma with extension into the sinuses and anterior cranial fossa. B, Axial contrast-enhanced CT scan in the same patient.

CT scanning may demonstrate bone involvement in lacrimal tumors, including pleomorphic adenoma, adenoid cystic carcinoma, adenocarcinoma, and mucoepidermoid carcinoma.28 When bone involvement is present, pleomorphic adenoma demonstrates smooth bone scalloping and remodeling. Irregular bone destruction raises the suspicion of malignant tumors. A study by Hesselink and coworkers28 revealed variable enhancement in both inlammatory (Fig. 20-53) and neoplastic lesions, and therefore enhancement is not a reliable predictor of aggressive pathology. Both pleomorphic adenoma and adenoid cystic carcinoma can demonstrate intense enhancement (see Fig. 20-51). The malignant

mucoepidermoid can demonstrate marked enhancement, but the adenocarcinoma may show no enhancement.

INDIRECT INVOLVEMENT OF THE ORBIT AND OPTIC PATHWAYS The orbit or any part of the optic pathways may be affected by adjacent intracranial lesions. The most common lesions arise from the sella turcica and parasellar regions. The differential diagnosis includes pituitary macroadenoma (Fig. 20-54), meningioma, craniopharyngioma, metastasis, aneurysm, chordoma, and other less common entities. The

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REFERENCES

FIG 20-53 Axial contrast-enhanced CT study shows lacrimal gland pseudotumor with extension to preseptal soft tissues on the right (arrowheads).

M

FIG 20-54 Pituitary macroadenoma (M) compressing on the optic chiasm, causing gradual visual loss in this patient. Arrows, optic nerves.

FIG 20-55 Axial T1-weighted MRI study with Gd shows left sphenoid wing meningioma (arrows), with compromise of the optic canal (curved arrow).

posterior optic apparatus—superior colliculi, lateral geniculate bodies (see Fig. 20-18), optic radiation, and occipital lobes—may be affected by any iniltration or mass lesion (e.g., tumor, infarction, or inlammatory process). One of the more common locations of an intracranial meningioma is the sphenoid wing. Visual symptoms can result from proximity to the optic canal or by mass effect on the anterior optic apparatus. Direct extension into the orbit is also possible (Fig. 20-55).

1. Ansari SA, Pak J, Shields M: Pathology and imaging of the lacrimal drainage system. Neuroimaging Clin N Am 15:221–237, 2005. 2. Barnes P, Robson C, Robertson R, et al: Pediatric orbital and visual pathway lesions. Neuroimaging Clin N Am 6:179–198, 1996. 3. Beck RW, Arrington J, Murtagh F: Brain magnetic resonance imaging in optic neuritis: Experience of the optic neuritis study group. Arch Neurol 50:841–846, 1993. 4. Belden CJ: MR imaging of the globe and optic nerve. Magn Reson Imaging Clin N Am 10:663–678, 2002. 5. Bilaniuk LT: Vascular lesions of the orbit in children. Neuroimaging Clin N Am 15:107–120, 2005. 6. Bond JB, Haik BG, Mihara F: Magnetic resonance imaging of choroidal melanoma with and without gadolinium contrast enhancement. Ophthalmology 98:459–466, 1991. 7. Boyce SW, Platia EV, Green WR: Drusen of the optic nerve head. Ann Ophthalmol 10:645–704, 1978. 8. Chutorian AM, Schwartz JF, Evans RA, et al: Optic gliomas in children. Neurology 14:83–95, 1964. 9. Collison JMT, Miller NR, Green WR: Involvement of orbital tissues by sarcoid. Am J Ophthalmol 102:302–307, 1986. 10. Conneely MF, Mafee MF: Orbital rhabdomyosarcoma and simulating lesions. Neuroimaging Clin N Am 15:121–136, 2005. 11. Coupland SE: T-cell and T/natural killer cell lymphomas involving ocular and ocular adnexal tissues: A clinicopathologic, immunohistochemical, and molecular study of seven cases. Ophthalmology 106:2109–2120, 1999. 12. Courcoutsakis NA, Langford CA, Sneller MC, et al: Orbital involvement in Wegener granulomatosis: MR indings in 12 patients. J Comput Assist Tomogr 21:452–458, 1997. 13. Curtin HD: Pseudotumor. Radiol Clin North Am 25:583–599, 1987. 14. Del Grande F, Santini F, Herzka DA, et al: Fat suppression techniques for 3-T MR imaging of the musculoskeletal system. Radiographics 34(1):217–233, 2014. 15. DiMario FJ, Ramsby G, Grennastein R, et al: Neuroibromatosis type I: Magnetic resonance imaging indings. J Child Neurol 8:32–39, 1993. 16. Ettl A, Kramer J, Daxer A, et al: High resolution magnetic resonance imaging of neurovascular orbital anatomy. Ophthalmology 104:869–877, 1997. 17. Flanders AE, Mafee MF, Rao VM, et al: CT characteristics of orbital pseudotumors and other orbital inlammatory processes. J Comput Assist Tomogr 13:40–47, 1989. 18. Font RL, Patipa M, Rosenbaum PS, et al: Correlation of computed tomographic and histopathologic features in malignant transformation of benign mixed tumor of lacrimal gland. Surv Ophthalmol 34(6):449– 452, 1990. 19. Forbes GS: Vascular lesions in the orbit. Neuroimaging Clin N Am 6:113–122, 1996. 20. Graeb DA, Rootman J, Robertson WD, et al: Orbital lymphangiomas: Clinical, radiologic, and pathologic characteristics. Radiology 175:417– 421, 1990. 21. Haik BG, Saint Louis L, Bierly J, et al: Magnetic resonance imaging in evaluation of optic nerve gliomas. Ophthalmology 94:709–717, 1987. 22. Handler LC, Davey IC, Hill JC, et al: The acute orbit: Differentiation of orbital cellulites from subperiosteal abscess by computed tomography. Neuroradiology 33:15–18, 1991. 23. Harnsberger HR: Handbook of head and neck imaging, ed 2, St. Louis, 1995, Mosby. 24. Harris GJ, Sakol PJ, Bonavolonta G, et al: An analysis of thirty cases of orbital lymphangioma: Pathophysiologic considerations and management recommendations. Ophthalmology 97:1583–1592, 1990. 25. Haynes BF, Fishman ML, Fauci AS, et al: The ocular manifestations of Wegener’s granulomatosis. Am J Med 63:131–141, 1977. 26. Henderson JW: Orbital cysts. In Orbital tumors, ed 2, New York, 1980, BC Decker, pp 75–115. 27. Herrick RC, Hayman LA, Taber KH, et al: Artifacts and pitfalls in MR imaging of the orbit: A clinical review. Radiographics 17:707–724, 1997.

CHAPTER 20 28. Hesselink JR, Davis KR, Dallow RL, et al: Computed tomography of masses in the lacrimal gland region. Radiology 131:143–147, 1979. 29. Hesselink JR, Davis KR, Weber AL, et al: Radiologic evaluation of orbital metastasis, with emphasis on computed tomography. Radiology 137:363–366, 1980. 30. Hilal SK, Trokel SL: Computerized tomography of the orbit using thin sections. Semin Roentgenol 12:137–147, 1977. 31. Hoffman GS, Kerr GS, Leavitt RY, et al: Wegener’s granulomatosis: An analysis of 158 patients. Ann Intern Med 116:488–498, 1992. 32. Johnson G, Miller DM, MacManus D, et al: STIR sequences in NMR imaging of the optic nerve. Neuroradiology 29:238–245, 1987. 33. Jones IS, Jacobiec FA, editors: Diseases of the orbit, New York, 1979, Harper & Row. 34. Katz SE, Rootman J, Vangveeravong S, et al: Combined venous lymphatic malformations of the orbit (so-called lymphangiomas): Association with noncontiguous intracranial vascular anomalies. Ophthalmology 105:176–184, 1998. 35. Kodilyne HC: Retinoblastoma in Nigeria: Problems in treatment. Am J Ophthalmol 63:467–481, 1967. 36. Koeller KK, Smirniotopoulos G: Orbital masses. Semin Ultrasound CT MR 19:272–291, 1998. 37. Koornneef L, Zonneveld F: The role of direct multiplanar high resolution CT in the assessment and management of orbital trauma. Radiol Clin North Am 25:753–766, 1987. 38. Kubal WS: The pathological globe: Clinical and imaging analysis. Semin Ultrasound CT MR 18:423–436, 1997. 39. Kubal WS: Imaging of orbital trauma. Radiographics 28:1729–1739, 2008. 40. Mafee MF: The orbit proper. In Som PM, Curtin HD, editors: Head and neck imaging, ed 4, St. Louis, 2003, Mosby, pp 193–259. 41. Mafee MF, Ainbinder D, Afshani E, et al: The eye. Neuroimaging Clin N Am 6:29–59, 1996. 42. Mafee MF, Goldberg MF, Greenwald MJ, et al: Retinoblastoma and simulating lesions: Role of CT and MR imaging. Radiol Clin North Am 25:667–682, 1987. 43. Mafee MF, Karimi A, Shah J, et al: Anatomy and pathology of the eye: Role of MR imaging and CT. Neuroimaging Clin N Am 15:23–47, 2005. 44. Mafee MF, Peyman GA: Retinal and choroidal detachments: Role of magnetic resonance imaging and computed tomography. Radiol Clin North Am 25:487–507, 1987. 45. Mafee MF, Peyman GA, McKusick MA: Malignant uveal melanoma and similar lesions studied by computed tomography. Radiology 156:404– 408, 1985. 46. Manfre L, de Maria M, Mangiameli A, et al: MR dacrocystography: Comparison with dacrocystography and CT dacrocystography. AJNR Am J Neuroradiol 21(6):1145–1150, 2000. 47. Mann I: Developmental abnormalities of the eye, ed 2, Philadelphia, 1957, JB Lippincott, pp 68–94. 48. McNichols MMJ, Power WJ, Griffen JF: Idiopathic inlammatory pseudotumor of the orbit: CT features correlated with clinical outcome. Clin Radiol 44:3–7, 1991. 49. Motton-Lippa L, Jakobiec FA, Smith M: Idiopathic inlammatory orbital pseudotumor in childhood: II. Results of diagnostic tests and biopsies. Ophthalmology 88:565–574, 1981. 50. Mulliken JB, Glowacki J: Hemangiomas and vascular malformations in infants and children: A classiication based on endothelial characteristics. Plast Reconstr Surg 69:412–420, 1982. 51. Nishino H, Rubino FA, DeRemee RA, et al: Neurological involvement in Wegener’s granulomatosis: An analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 33:4–9, 1993.

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52. Nugent RA, Belkin RI, Meigel JM, et al: Graves orbitopathy: Correlation of CT and clinical indings. Radiology 177:675–682, 1990. 53. Nugent RA, Lapointe JS, Rootman J, et al: Orbital dermoids: Features on CT. Radiology 165:475–478, 1987. 54. Pendergrass TW, Davis S: Incidence of retinoblastoma in the United States. Arch Ophthalmol 98:1204–1210, 1980. 55. Peyman GA, Mafee MF: Uveal melanoma and similar lesions: The role of magnetic resonance imaging and computed tomography. Radiol Clin North Am 25:471–486, 1987. 56. Provenzale JM, Mukherji S, Allen NB, et al: Orbital involvement by Wegener’s granulomatosis: Imaging indings. AJR Am J Roentgenol 166:929–934, 1996. 57. Ramirez H, Blatt ES, Hibri HS: Computed tomography identiication of calciied optic nerve drusen. Radiology 148:137–139, 1983. 58. Raymond WR, Char DH, Norman D, et al: Magnetic resonance imaging evaluation of uveal tumors. Am J Ophthalmol 111:633–641, 1991. 59. Roberts CF, Leehey PJ, III: Intraorbital wood foreign body mimicking air at CT. Radiology 185:507–508, 1992. 60. Rosenberg MA, Savino PJ, Glaser JS: A clinical analysis of pseudopapilledema: I. Population, laterality, refractive error, ophthalmoscopic characteristics and coincident disease. Arch Ophthalmol 97:65–70, 1979. 61. Rootman J: Vascular malformations of the orbit: Hemodynamic concepts. Orbit 22:103–120, 2003. 62. Rothfus WE, Kapoor V: Orbital masses, schemata for differential diagnosis. In Latchaw RE, Kucharczyk J, Moseley ME, editors: Imaging of the nervous system—Diagnostic and therapeutic applications, St. Louis, 2005, Mosby, pp 1007–1031. 63. Schulman JA, Peyman GA, Mafee MF, et al: The use of magnetic resonance imaging in the evaluation of retinoblastoma. J Pediatr Ophthalmol Strabismus 23:144–147, 1986. 64. Shields JA, Bakewell B, Augsburger JJ, et al: Classiication and incidence of space-occupying lesions of the orbit: A survey of 645 biopsies. Arch Ophthalmol 102:1606–1611, 1984. 65. Shnier R, Parker GD, Hallinan JM, et al: Orbital varices: A new technique for noninvasive diagnosis. AJNR Am J Neuroradiol 12:717–718, 1991. 66. Simmons JT, Leavitt R, Kornblat AD, et al: CT of the paranasal sinuses and orbits in patients with Wegener’s granulomatosis. Ear Nose Throat J 66:134–140, 1987. 67. Som PM, Brandwein MS: Inlammatory diseases. In Som PM, Curtin HD, editors: Head and neck imaging, ed 4, St. Louis, 2003, Mosby, pp 193–259. 68. Turner RM, Gutman I, Hilal SK, et al: CT of drusen bodies and other calciied lesions of the optic nerve: Case report and differential diagnosis. AJNR Am J Neuroradiol 4:175–178, 1983. 69. Vaidhyanath R, Kirke R, Brown L, et al: Lacrimal fossa lesions: Pictorial review of CT and MRI features. Orbit 27(6):410–418, 2008. 70. Valvassori GE: Imaging of orbital lymphoproliferative disorders. Radiol Clin North Am 37:135–150, 1999. 71. White JH, Fox AJ, Symons SP: Diagnosis and anatomic mapping of an orbital varix by computed tomographic angiography. Am J Ophthalmol 140:945–947, 2005. 72. Winter J, Centeno RS, Bentson JR: Maneuver to aid diagnosis of orbital varix by computed tomography. AJNR Am J Neuroradiol 3:39–40, 1982. 73. Wright JE, McNab AA, McDonald WI: Optic nerve glioma and the management of optic nerve tumours in the young. Br J Ophthalmol 73:967–974, 1989. 74. Youssei B: Orbital tumors in children: A clinical study of 62 cases. J Pediatr Ophthalmol 6:177–181, 1969.

21 Temporal Bone Ellen Hoeffner, Rickin Shah, Dilan Samarawickrama, and Suyash Mohan

EMBRYOLOGY AND DEVELOPMENT OF TEMPORAL BONE The ear consists of three major components, the external, middle, and internal ear. Embryologically the ear has a dual development with development of the inner ear structures (internal auditory canal [IAC], cochlea, vestibule, and semicircular canals [SCC]) independent of the middle and external ear structures (ossicles, middle ear air spaces, mastoid antrum, tympanic membrane [TM], external auditory canal [EAC], and temporomandibular joint [TMJ]). The neural soundperceiving apparatus of the inner ear develops from a thickened ectodermal placode. The mechanical sound-collecting and soundtransmitting structures of the external and middle ear, respectively, develop from the irst and second pharyngeal (branchial) arches and the intervening irst pharyngeal cleft and pharyngeal pouch. Adjacent mesenchyme contributes to the development of the inner, middle, and external ear.19 This explains why developmental abnormalities of the inner ear are usually not seen with deformities of the external and middle ear, and vice versa.10,81 The endolymphatic (membranous), perilymphatic (periotic), and bony labyrinths of the inner ear all develop from the ectodermal otic placode that invaginates to form the otocyst or otic vesicle. The otic vesicle elongates, forming a dorsal vestibular region and a ventral cochlear region. The endolymphatic duct also develops as a short projection from the dorsomedial surface of the otic vesicle.19 The perilymphatic labyrinth develops as mesenchyme surrounding the membranous labyrinth resorbs.23 The bony labyrinth (otic capsule) also develops from mesenchyme around the membranous labyrinth. This begins between 4 and 8 weeks’ gestation, continues to grow between 8 and 16 weeks’ gestation, and ossiies by week 24 of gestation.95 The external and middle ear develop from the pharyngeal apparatus. The irst pharyngeal groove deepens to become the primitive EAC and over time contributes to the development of the mature EAC, the outer layer of the TM, and the tympanic ring. The auricle or pinna develops around the irst pharyngeal groove from six nodular mesenchymal masses or hillocks arising from the irst and second pharyngeal arches.23 The irst pharyngeal pouch expands to form a tubotympanic recess.19 This tubotympanic recess gives rise to the eustachian tube, the tympanic cavity, the mastoid antrum, and their epithelial lining.23 Just dorsal to the end of the tubotympanic recess, a condensation of mesenchyme from the irst and second pharyngeal arches appears, which develops into the ossicles.19 The head and neck of the malleus and body and short process of the incus arise from the irst arch. The second arch forms Reichert’s cartilage, from which the remainder of the malleus and incus and the stapes superstructure develop. The stapes footplate is a bilaminar structure, with an outer portion developing

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from Reichert’s cartilage and an inner portion developing from the ectodermal otocyst.23 The middle ear cavity and mastoid antrum are luid illed until birth. The neonate’s initial crying and breathing ill the eustachian tube system and the middle ear with air. The mastoid air cells develop as saclike extensions from the mastoid antrum, commencing around the time of birth and continuing for several years.

NORMAL TEMPORAL BONE ANATOMY External Auditory Canal The EAC consists of a funnel-shaped, undulating, cartilaginous lateral portion and an osseous medial segment (Figs. 21-1 through 21-5; see Figs. 21-1B, 21-2C, 21-3A, 21-5A). The cartilaginous portion is continuous with the auricle, lexible and surrounded by fat. The osseous portion, surrounded by the tympanic portion of the temporal bone, constitutes two thirds of the length of the EAC and is covered by skin and periosteum only. The EAC extends medially to the TM. The TM attaches to an annular ridge of bone termed the tympanic anulus.50

Middle Ear Cavity and Mastoid The tympanic cavity, or middle ear, is the air space within the petrous portion of the temporal bone between the eustachian canal anteriorly and the mastoid air cells posteriorly that contains the ossicles (see Figs. 21-1D-G, 21-2C-F, 21-3B, 21-4D). Its other borders consist of the TM laterally, otic capsule and cochlear promontory medially, tegmen tympani superiorly, and jugular loor inferiorly. The middle ear cavity can be subdivided into three spaces—hypotympanum, mesotympanum, and epitympanum—based on the relationship to the TM (see Fig. 21-2C). The hypotympanum is the most inferior portion of the tympanic cavity, inferior to the level of the TM, and connects anteromedially to the opening of the eustachian tube. The semicanal for the tensor tympani muscle is parallel and superior to the eustachian tube (see Fig. 21-2A).50 This muscle arises from the superior surface of the cartilaginous eustachian tube and courses posteriorly in the medial portion of the middle ear, turning sharply laterally at the level of the neck of the malleus, to which it attaches. The thin plate of bone separating these two semicanals is termed the cochleariform process (see Figs. 21-1F and 21-2B-C).23 The mesotympanum, the central portion of the tympanic cavity, is medial to the TM. It is bordered laterally by the scutum (or spur) and TM and medially by the otic capsule. The scutum is a bony crest separating the EAC from the epitympanic space (see Fig. 21-2C-D). The TM attaches to the scutum superiorly and to the limbus inferiorly. The mesotympanum contains the majority of the ossicles. Text continued on p. 623

CHAPTER 21

Temporal Bone

Petrooccipital fissure

Condyle and TMJ

condyle

* *

*

*

Carotid canal

EAC Carotid canal

Cochlear aqueduct Descending VII

Descending VII Jugular foramen

B

A

Carotid canal Tensor tympani muscle Manubrium Long process

Tympanic membrane

1 Descending VII

Round window niche

2

***

Basal turn

Pyramidal eminence Vestibular aqueduct

C

D FIG 21-1 Axial CT images from caudal to cranial. A, Jugular foramen level. The caroticojugular spine separates the carotid canal and jugular foramen. The descending facial nerve canal (descending VII) is lateral to the jugular foramen. The mandibular condyle and temporomandibular joint (*) are seen. B, Inferior tympanic level. The eustachian canal (black arrows) and its opening into the hypotympanum (*) are visualized just lateral to the carotid canal. A portion of the external auditory canal (EAC) is seen just anterior to the descending facial nerve canal (descending VII). The mandibular condyle and TMJ are seen anterior to the EAC. The cochlear aqueduct and petrooccipital issure are seen. C-E, Midtympanic level. The descending portion of the facial nerve canal (descending VII) is seen posterior to the pyramidal eminence (C, D). The facial nerve recess (1) can be seen lateral to and the sinus tympani (2) medial to the pyramidal eminence (D). Continued

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Tensor tympani t. Ant. crus 3 4

Manubrium

5 Post. crus

Long process Stapes

E

F

Interscalar septae

Tympanic VII m

mo

i v

IAC

Singular canal

G

H FIG 21-1, cont’d The manubrium of the malleus (manubrium) is anterior to the long process of the incus (long process) (D, E). The stapes suprastructure is medial to the incus (E). The apical (3), middle (4), and basal (5) turns of cochlea and round window niche are seen with overlying cochlear promontory (*) (C-E). The tensor tympani muscle is lateral and parallel to the carotid canal (C). F-J, Epitympanic–internal auditory canal level. The anterior (ant. crus) and posterior (post. crus) crura of stapes are seen extending to oval window; the tensor tympani tendon (tensor tympani t.) attaches to neck of malleus (F). At the incudomalleolar articulation the “ice-cream-cone” coniguration of the head of malleus (m) and body and short process of incus (i) is seen (G). The modiolus (mo) and interscalar septae of the cochlea are seen along with the cochlear nerve canal (black arrowheads) (H).

CHAPTER 21

Tympanic VII

L S S C

*

Temporal Bone

Labyrinthine VII

Sup. vest. nerve c.

V

J

I

SSCC Aditus

Common crus

Antrum

PSCC

K

L FIG 21-1, cont’d The vestibule (v) and lateral semicircular canal (LSSC) are seen as are the canals for the superior (sup. vest. nerve c.) and inferior (singular canal) vestibular nerves as the exit the internal auditory canal (IAC) (G-I). The labyrinthine segment (labyrinthine VII), anterior genu (*) and tympanic segment (tympanic VII) of the facial nerve canal are seen in their characteristic course (G, J). K and L, Mastoid antrum level. The aditus ad antrum (aditus) is seen connecting the mastoid antrum and epitympanum (K). Portions of the posterior (PSSC) and superior (SSSC) semicircular canals and their shared common crus are visualized (K, L).

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Geniculate ganglion Tensor tympani Cochlea

* *

Tensor tympani

Carotid canal

*

Carotid canal

Cochleariform process

Condyle Eustachian tube

A

B

Tympanic VII TT tendon T

*

L

Cochlea Cochlea

N

** Incus LP

EAC

C

D FIG 21-2 Coronal CT images from anterior to posterior. A, Temporomandibular joint (TMJ) level. The tensor tympani muscle is seen in its semicanal just above the eustachian tube. The TMJ (*), mandibular condyle (condyle) and carotid canal are seen. B, Geniculate ganglion level. The tensor tympani muscle and cochleariform process are seen along medial wall of middle ear. The geniculate ganglion is seen as a small lucency just superior to anteriormost portion of cochlea. The carotid canal is just inferior to the cochlea. C, Anterior tympanic level. The external auditory canal (EAC) and tympanic membrane (TM) (white arrowheads) are seen, with the TM attaching to the scutum (*) superiorly. The malleus is seen, with the tensor tympani tendon (TT tendon) attaching to the neck (N) of the malleus. The labyrinthine (L) and tympanic (T) segments of facial nerve canal are seen as two lucencies superior to cochlea. D-E, Midtympanic level. The long process of the incus is seen (incus LP), forming the medial border of Prussak’s space (white *); the scutum (black *) forms the lateral border of this space (D).

CHAPTER 21

Temporal Bone

Superior SCC Tympanic VII

Oval window

Lateral SCC

Crista falciformis

IAC V Tympanic VII Stapes I-S joint

E

F

Antrum

Superior SCC

Pyramidal eminence Lateral SCC 1

2

Round w. niche

G

Jugular foramen

H FIG 21-2, cont’d The lenticular process of the incus and head of the stapes form the incudostapedial joint (I-S joint) (E). The tympanic segment of the facial nerve canal (tympanic VII) is seen superolateral to the cochlea and cochlear promontory (black arrowheads) (D, E). F, Oval window level. The internal auditory canal (IAC) is visualized divided by the crista falciformis. The oval window is seen along the lateral margin of the vestibule (v), with the stapes extending toward it. The tympanic segment of the facial nerve canal (tympanic VII) is seen just below the lateral SCC. The anterior limb of the superior SCC is also seen. G, Posterior tympanic level. The facial nerve recess (1) is lateral to and the sinus tympani (2) medial to the pyramidal eminence. The round window niche (round w. niche) is seen along the basal turn of the cochlea. H, Jugular foramen level. The mastoid segment of the facial nerve canal (black arrowheads) is seen in its vertical course. Parts of the lateral SCC and superior SCC are seen. The mastoid antrum and jugular foramen are seen.

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PART II CT and MR Imaging of the Whole Body

Malleus

Incus

Lateral SCC

E A C

Condyle

B

A

Common crus

Cochlea

Superior SCC

I A C

V. aqueduct V

*

Carotid canal Jugular foramen

C

D FIG 21-3 Sagittal CT images from lateral to medial. A, External auditory canal (EAC) level. The EAC is posterior to the TMJ composed of the glenoid fossa (arrowheads) and the mandibular condyle (condyle). B, Descending facial nerve canal level. The posterior genu and descending facial nerve canal (arrowheads) have an upside-down hockey-stick shape, and the malleus and incus together have a molar tooth coniguration. Part of the lateral SCC is seen. C, Vestibule level. The vestibule (V) is central, with the common crus and a portion of the superior SCC posterior to the vestibule. The round window (arrowhead) is just posterior to the basal turn of the cochlea (*). The vestibular aqueduct (V. aqueduct) is seen along the posterior margin of the petrous bone. D, Internal auditory canal (IAC) level. The IAC is seen as an oval lucency posterior to a portion of the cochlea. The carotid canal and jugular foramen are seen.

Superior SCC

Superior SCC Posterior SCC

Common crus

A

B

Incudomallear joint

Cochlea

I M

C

D Superior SCC

Posterior SCC

m

Tympanic VII

E

F FIG 21-4 Stenvers’ and Pöschl’s views. A, Stenvers’ view midsuperior SCC level. The superior SCC is seen in cross section. B, Stenvers’ view common crus level. In addition to common crus, portions of the posterior SCC and superior SCC are seen. C, Stenvers’ view cochlea level. The turns of the cochlea are seen, as is the round window (arrowhead) and descending facial nerve canal (arrows). D, Stenvers’ view incudomalleolar joint level. The incudomalleolar joint is well seen between body of incus (I) and head of malleus (M). E, Pöschl’s view midsuperior SCC level. The superior SCC is seen as a ring, and the posterior SCC is seen in cross section. The tympanic segment of the facial nerve canal is seen in cross section (tympanic VII). F, Pöschl’s view modiolus level. The modiolus (m) is seen along its axis.

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Cochlea

* EAC

** Posterior SCC Endolymphatic duct

A

B

Cochlea

Cochlear n.

* V Lateral SCC Posterior SCC

C

Inferior vestibular n.

D FIG 21-5 Axial MRIs from caudal to cranial. A, Jugular foramen level, postcontrast T1-weighted image. The descending portion of the facial nerve is seen in cross section (arrow) as a focus of intermediate signal lateral to the jugular bulb (**), which has mixed signal. Mixed signal also seen in internal carotid artery (*). The EAC can be seen. B, Midtympanic level, T2-weighted image. Inner ear structures (cochlea and posterior SCC) are of high signal, as is endolymphatic duct. C, Epitympanic level, T2-weighted image. Inner ear structures (cochlea, vestibule [V], lateral SCC, and posterior SCC) are of high signal; modiolus (*) is seen as a low-signal structure within cochlea. The cochlear nerve (cochlear n.) and inferior vestibular nerve (inferior vestibular n.) are seen as linear low-signal structures in luid-illed IAC. D, Epitympanic level, T1-weighted postcontrast image. The geniculate ganglion (long arrow) and tympanic segment of the facial nerve (short arrows) are of intermediate signal. The IAC can be seen medially.

CHAPTER 21 The triangular epitympanum forms the superior portion of the middle ear, superior to the level of the TM. It contains the head of the malleus and the body and short process of the incus (see Fig. 21-1G). The posterior wall of the cavity is irregular and contains the facial nerve recess laterally and the sinus tympani medially, separated by the pyramidal eminence. The pyramidal eminence overlies the stapedius muscle, which inserts onto the head of the stapes (see Figs. 21-1D and 21-2G). Prussak’s space is another important area of the middle ear cavity bounded by the scutum and pars laccid of the TM laterally, the neck of the malleus medially, and the lateral malleal ligament superiorly (see Fig. 21-2D). The cone-shaped antrum is located in the anterosuperior part of the mastoid portion of the temporal bone and communicates with the epitympanum via a narrow channel termed the aditus ad antrum. The antrum is surrounded by smaller variable-sized mastoid air cells (see Fig. 21-1K).23 The size of the antrum varies considerably as a result of the alterations in pneumatization of the air cells that drain into it. The antrum is bordered superiorly by the tegmen tympani. The medial margin of the antrum is the promontory formed by the otic capsule of the lateral SCC. The mastoid air cells are divided by Koerner’s septum, a thin bony structure formed by the petrosquamous suture that extends posteriorly from the epitympanum, into medial and lateral components.

Ossicles The ossicles are suspended by the TM, the ossicular ligaments to the epitympanic walls, and the oval window. The manubrium (or handle) and lateral process of the malleus attach to the TM. The neck of the malleus is connected to the tensor tympani tendon (see Fig. 21-2C). The anterior malleal ligament attaches the head of the malleus to the anterior epitympanic wall; the superior malleal ligament attaches the head to the roof of the middle ear cavity. The lateral malleal ligament attaches the head or neck of the malleus to the tympanic notch, a defect in the superior portion of the tympanic anulus.50,56 The circular head of the malleus articulates with the triangular body of the incus (see Figs. 21-1G and 21-3B). The short process of the incus projects posteriorly and is suspended within the epitympanic space, pointing toward the aditus ad antrum. The posterior incudal ligament attaches the short process to the fossa incudis, a small depression in the posteroinferior part of the epitympanic recess. The long process of the incus projects inferiorly, parallel to and behind the manubrium of the malleus (see Fig. 21-2D). The tip of the long process bends medially to end in the lenticular process, which articulates with the head of the stapes (see Fig. 21-2E). The stapes consists of the head, two crura, and a footplate (see Figs. 21-1E and F). The footplate of the stapes attaches to the oval window of the vestibule and is secured by the annular ligament (see Fig. 21-2F).

Inner Ear The inner ear is located within the petrous portion of the temporal bone and comprises the osseous labyrinth, which consists of the cochlea, vestibule, and SCCs. The osseous labyrinth encapsulates the membranous labyrinth, which contains endolymph and is surrounded by perilymph. The vestibular cavity is the central portion of the membranous labyrinth that communicates with the SCCs and cochlea (Fig. 21-6; see Figs. 21-1G, 21-1I, 21-2F, 21-3C, 21-5C, 21-6A). The vestibule lies immediately lateral to the fundus of the IAC, and the oval window of the middle ear forms its lateral margin. The vestibular aqueduct is a narrow bony canal that contains the small endolymphatic duct and sac (see Figs. 21-1C, 21-3C, 21-5B). The endolymphatic duct originates

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Superior SCC

Lateral SCC Cochlea

A

B FIG 21-6 Coronal MRIs from anterior to posterior. A, Oval window level, T2-weighted image. The IAC (arrowheads) is of high signal, with low-signal nerves traversing it. The inner ear structures (vestibule [V], superior SCC, lateral SCC, and cochlea) are of high signal. B, Oval widow level, T1-weighted postcontrast image. The IAC (arrowheads) is of intermediate signal.

from the posteromedial aspect of the vestibule, courses past the common crus, and assumes a hockey-stick shape. The endolymphatic sac, an extension of the endolymphatic duct, is a dead-end luid space arising from the vestibule that lies beneath the dura of the posterior temporal bone. The bony vestibular aqueduct surrounds the endolymphatic duct.50 The SCCs are three orthogonally arranged circular structures of the membranous labyrinth arising from the vestibule. The lateral SCC approximates the horizontal plane (see Fig. 21-1I). The posterior and superior SCCs share a crus posteriorly, formed by a fusion of the posterior crus of the superior SCC and the anterior crus of the posterior SCC (see Figs. 21-1K, 21-2F, 21-3C, 21-4B). The vestibule and SCCs are responsible for balance and equilibrium. The oval window of the vestibule is the interface between the mechanical and neural elements of the ear (see Fig. 21-2F). It lies just inferior to the horizontal facial nerve canal and the lateral SCC. It is covered by the annular ligament, which surrounds the footplate of the stapes. The spiral cochlear apparatus contains the membranous labyrinth components for hearing. The cochlea lies anterior to the vestibule and has 2.5 to 2.75 turns (basal, middle, and apical) around its modiolus, the central bony spiral axis. The turns of the cochlea are separated by interscalar septae (see Figs. 21-1E and H, 21-2C, 21-4C, 21-5B and C). The most lateral portion of the basal turn of the cochlea projects into the tympanic cavity, forming a promontory of bone (see Figs. 21-1D, 21-2E). The round window is the bony opening of the basal turn of the cochlea into the middle ear, lying inferior and slightly posterior to the oval window and covered by a ibrous membrane (see

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1

2

3

4

FIG 21-7 IAC level, sagittal T2-weighted image. The high-signal IAC is seen in cross section, with the facial (1), cochlear (2), superior vestibular (3) and inferior vestibular (4) nerves seen within.

Figs. 21-1C, 21-2G, 21-3C). The cochlear nerve passes from the IAC through the bony canal for the cochlear nerve into the modiolus (see Figs. 21-1H, 21-5C). The cochlear aqueduct, a channel that connects the cochlea near the round window with the subarachnoid space just superior to the jugular tubercle, lies inferior to the IAC (see Fig. 21-1B).

Internal Auditory Canal The IAC is a bony conduit within the petrous portion of the temporal bone that transmits cranial nerves VII (facial) and VIII (vestibulocochlear) from the pontomedullary junction of the brainstem across the cerebellopontine angle (CPA) cistern to the inner ear (Fig. 21-7; see Figs. 21-1G, 21-2F, 21-5C, 21-6A and B). Its medial oriice is the porus acusticus. The IAC is partially divided by a transverse bony crest called the crista falciformis (see Fig. 21-2F), which runs parallel to the long axis of the canal and divides it into a superior and inferior portion. A vertical crest termed Bill’s bar divides the superior component into anterior and posterior parts. The facial nerve is located in anterosuperior compartment, the cochlear nerve in the anteroinferior compartment, and the superior and inferior vestibular nerves in the posterosuperior and posteroinferior compartments, respectively (see Fig. 21-7). The lateral portion of the canal or fundus is perforated by the cranial nerves where they enter the cochlea, vestibule, and facial nerve canal (see Fig. 21-1H-J). The IACs should be nearly symmetric. Although there is wide variation in the exact shape and size of the canals, asymmetry of greater than 2 mm suggests pathology.

Facial Nerve and Facial Nerve Canal The facial nerve has a highly tortuous course and comes in close contact with almost every other important component of the temporal

bone. It may be described as having six segments: cisternal, intracanalicular, labyrinthine, tympanic, mastoid, and extracranial. The facial nerve departs the brainstem at the lower border of the pons at the pontomedullary junction. Within the CPA cistern, the cisternal facial nerve is the most anterior and the vestibulocochlear nerve is the most posterior, with the nervus intermedius between the two. The facial nerve then enters the porus acusticus of the IAC and traverses the IAC in its intracanalicular segment (see Fig. 21-7). The labyrinthine portion of the facial nerve exits the superior anterior portion of the IAC fundus and follows an anterolaterally curving course in the fallopian canal to the geniculate ganglion. The greater supericial petrosal nerve also arises from the geniculate ganglion (see Figs. 21-1J, 21-2B and C, 21-5D). At the geniculate ganglion, an acute reverse (inverted V) angle of the nerve and canal is seen. The distal limb of the facial nerve doubles back posteriorly to become the tympanic segment in the medial wall of the tympanic cavity (see Figs. 21-1C, 21-2D-F, 21-5D). This portion of the facial nerve canal has a thin inferior bony covering that may be dehiscent. The tympanic portion of the facial nerve runs horizontally directly inferior to the lateral SCC. The facial nerve then abruptly turns inferiorly (at an angle of 95 to 125 degrees) to form the posterior genu near the sinus tympani and the pyramidal eminence (see Fig. 21-3B). The vertical, or descending, facial nerve in the mastoid portion of the facial nerve canal runs vertically just posterior to the EAC. In this vertical portion, the nerve to the stapedius muscle and the chorda tympani (the irst and second branches, respectively, of the facial nerve distal to the geniculate ganglion) arise (see Figs. 21-1A-C, 21-2H, 21-5A). The facial nerve then exits the mastoid portion of the temporal bone via the funnel-shaped fat-illed stylomastoid foramen. The extracranial portion of the facial nerve delivers branches to the muscles and pierces the parotid gland to form the parotid plexus.

Carotid Canal The carotid canal enters the base of the skull, ascends vertically, then turns horizontally and medially toward the petrous apex (see Figs. 21-1A-C, 21-2A and B, 21-3D, 21-5A). This canal lies anterior and inferior to the cochlea and is separated from the middle ear cavity by a thin bony plate.

Jugular Foramen and Fossa The jugular foramen is divided into a smaller anteromedial neural compartment (pars nervosa) containing cranial nerves IX, X, and XI, and a larger posterolateral vascular compartment (the pars vascularis) containing the jugular vein. The loor of the tympanic cavity normally forms the roof of the jugular fossa. The jugular bulbs are frequently asymmetric, and there may be a small diverticulum from their apices (see Figs. 21-1A, 21-2H, 21-3D, 21-5A).

TEMPORAL BONE IMAGING TECHNIQUES Computed tomography (CT) and magnetic resonance imaging (MRI) are currently the most widely used techniques for imaging the temporal bone, having largely replaced the former modalities. CT and MRI studies are complementary. Each technique has advantages and disadvantages, and often more than one examination is necessary for a complete temporal bone evaluation. CT is excellent for assessing the osseous structures of the temporal bone but not ideal for evaluating the soft tissue contents of the otic capsule, brain, or vessels. In contrast, MRI is superior to CT in characterizing the cerebrospinal luid (CSF), brain, and cranial nerves. CT and MR angiography can be used to assess vascular structures.

CHAPTER 21

Computed Tomography The temporal bone has a high inherent contrast resolution, having both the densest bone in the body and air-illed spaces. High-spatialresolution CT scanning is the best method for evaluating bone and air space anatomy and disorders. A major advance in CT technology was achieved with the introduction of multidetector-row helical CT. Compared to earlier CT techniques, multidetector CT provides improved quality of the axial source images as well as two- and three-dimensional (2D and 3D) reconstructions; this is due to a reduction in partial volume and motion artifacts and higher resolution along the z-axis with nearly isotropic voxel size.48,113 Multiplanar CT reformations can display the complex anatomy of the temporal bone in all planes while exposing the patient to radiation only once.54,62 High-resolution CT images are usually acquired with thin sections (0.5-1 mm) and special bone algorithms for high detail. At the authors’ institution, scans are acquired in the axial plane in the helical mode with a slice thickness of 0.625 mm. The image data set is reconstructed into magniied axial, sagittal, and coronal images with 0.625-mm thickness at an interval of 0.312 mm. Contrast enhancement is not essential for evaluation of pathology isolated to bone or air spaces. For some clinical indications, additional reconstructed images are obtained in the planes of Stenvers and Pöschl (see Fig. 21-4A-F). Stenvers’ plane is perpendicular to the superior SCC. Pöschl’s plane is parallel to the superior SCC.23 Oblique reformatted images can be obtained in virtually any other plane to highlight speciic structures of the temporal bone.54 The high contrast between the bony structures and the air spaces allows for virtual endoscopy of the middle ear by using surfacerendering technique. Axial images and 2D reformatted images remain the main modality for evaluating temporal bone structures and pathology. 3D reformatted virtual endoscopy (VE) images may serve as an adjunct in assessing the temporal bone, particularly in assessing the ossicular chain and possibly the round window; however, the overall sensitivity and speciicity of this technique for detecting middle ear abnormalities is 59% and 25%, respectively.41 VE images may be of additional beneit to surgeons because they are more similar to their visual view in the operating room. VE images may also be helpful in teaching and in ear surgery simulators.62

Magnetic Resonance Imaging MRI also has revolutionized the temporal bone examination and expanded the range of pathology that can be accurately evaluated, because it can image many soft tissue entities. It is much better than CT in characterizing the CSF, brain, and cranial nerves, and it can be useful in the evaluation of blood vessel–related disorders of the temporal bone. Many different techniques can be used to acquire MRIs, depending on the suspected abnormality and the equipment available. T2-weighted (repetition time [TR] = 3000 milliseconds or longer; echo time [TE] = 80 milliseconds or longer) axial spin echo images display the CSF and endolymphatic spaces and many disease processes as highsignal-intensity regions. Submillimeter images can be obtained using a 3D turbo-spin echo (TSE)/fast-spin echo (FSE) sequences.20 These sequences display the otic capsule structures as high-signal-intensity regions surrounded by signal void. The facial nerve and the three branches of the vestibulocochlear nerve can be distinguished inside the IAC. This type of sequence is often used as a screening technique for vestibular schwannomas.1 T1-weighted (TR = 600 milliseconds, TE = 20 milliseconds) spin echo coronal or axial images are often acquired before and after administration of gadolinium-based contrast agent. The fat spaces have high

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signal intensity, and the brain has intermediate signal intensity. CSF demonstrates low signal intensity, and air and bone spaces appear as voids. Postcontrast T1-weighted images are particularly sensitive for evaluating abnormalities that alter the blood-brain barrier or are vascular. The sensitivity of contrast-enhanced T1-weighted images to detect these lesions can be exaggerated by using fat-saturation techniques.64

Normal Temporal Bone Images Axial Images: Caudal to Cranial Axial jugular foramen level (see Figs. 21-1A, 21-5A). CT: The carotid canal lies just anterior to the jugular fossa, forming a “snowman”-like coniguration. Both demonstrate sharp cortical margins. Inferiorly only a small spine, the caroticojugular spine, separates the two as they converge to enter the carotid sheath. The descending facial nerve canal is lateral to the jugular foramen, seen as a rounded well-corticated lucency. The mandibular condyle and TMJ can also be seen.23,39 MRI: The descending portion of the facial nerve can be seen just lateral to the jugular bulb on T1- and T2-weighted images as an intermediate- to high-signal rounded structure. The blood vessels generally demonstrate signal void due to low but may be seen as areas of intermediate to high signal if slow or turbulent low is present.23,39 Axial inferior tympanic level (see Fig. 21-1B). CT: The opening of the eustachian canal is triangular, with the apex extending parallel to the carotid canal and communicating with the anterior hypotympanum. The anterior and posterior walls of the bony EAC demonstrate dense, sharp cortical margins without soft tissue covering. The anterior margin of the EAC forms the posterior lip of the TMJ. The medial funnel-shaped opening of the cochlear aqueduct can be seen as a triangular lucency facing the CPA, progressively enlarging from lateral to medial. The opening of the aqueduct may be large and mimic the IAC. The descending facial nerve canal is easily identiied posterior to the EAC. The petrooccipital issure separates the temporal bone from the occiput.23,39 MRI: The facial nerve is seen as an intermediate- to high-signalintensity circular structure surrounded by a large area of signal void of the temporal bone and mastoid air spaces. The cochlear aqueduct is not well seen on MRI studies, possibly because of the combination of its small diameter and CSF motion artifacts.23,39 Axial midtympanic level (see Figs. 21-1C-E, 21-5B). CT: The carotid canal can be seen early in its anteromedial course through the skull base, parallel and medial to the semicanal of the tensor tympani muscle at this level. The normally thin TM may be visible. The manubrium of the malleus parallels the TM. The manubrium of the malleus lies parallel and anterior to the long process of the incus. The stapedial superstructure (head, crura, and tympanic portion of the footplate) is often seen, forming an arch over the oval window. The cochlear promontory can be seen along the complex medial wall of the middle ear. Along the posterior wall of the middle ear is the pyramidal eminence, with the facial nerve recess lateral and the sinus tympani medial to the eminence. The descending facial nerve canal can be seen just posterior to the pyramidal eminence. The apical, middle, and basal cochlear turns are seen at this level along with the round window niche at the basal turn. The vestibular aqueduct is seen as a thin bony lucency along the posterior margin of the temporal bone, near its opening to the posterior cranial fossa.23,39 MRI: The cochlea is seen as a high-signal-intensity structure on T2-weighted images. The endolymphatic duct and sac may be seen as a tubular, thin, high-signal-intensity structure along the posterior margin of the temporal bone. The middle ear and its contents are not well seen unless illed with luid.23,39

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Axial epitympanic–internal auditory canal level (see Figs. 21-1F-J, 21-5C and D). CT: The crura of the stapes can be seen extending toward the oval window, and the tensor tympani tendon can be seen making a 90-degree turn and attaching to the neck of the malleus. At the level of the incudomalleolar articulation, the round head of the malleus and the triangular body and short process of the incus are seen in their characteristic “ice cream cone” coniguration. The lateral SCC is seen protruding into the middle ear. The modiolus and interscalar septae of the cochlea are visualized, as is the vestibule, posterolateral to the cochlea. The IAC is slightly funnel-shaped and ends in an ovoid fundus. The canals for the facial nerve, cochlear nerve, superior vestibular nerve, and inferior vestibular nerve (singular canal) can be seen leaving the fundus of the IAC. The labyrinthine segment of the facial nerve canal (fallopian canal) can be seen extending to the anterior genu, and the tympanic segment is seen coursing along the medial wall of the tympanic cavity.23,39 MRI: MRI studies demonstrate CSF in the IAC, and with highresolution images the individual nerves are seen as low-signal illing defects within the CSF. The luid contents of the cochlea, vestibule, and SCCs are seen as high signal on T2-weighted images. The modiolus and interscalar septae are seen as areas of low signal within the otherwise bright cochlea. The geniculate ganglion and horizontal segment of the facial nerve are seen as intermediate-signal-intensity structures surrounded by the signal void resulting from their bony walls on T1-weighted images.23,39 Axial mastoid antrum level (see Fig. 21-1K and L). CT: The aditus ad antrum is situated between the epitympanum and mastoid antrum. The mastoid antrum lies posterior and lateral to the aditus ad antrum and opens into many mastoid air cells. On CT scans, the posterior SCC and common crus of the posterior and superior SCCs can be seen. More superiorly the superior SCC is present.23,39 MR: Portions of the SCCs are seen as areas of high signal on T2-weighted images.23,39

Coronal Images: Anterior to Posterior Coronal temporomandibular joint level (see Fig. 21-2A). CT: The horizontal carotid canal is seen as an oval structure just lateral to petrooccipital suture. The semicanal for the tensor tympani muscle is seen as a small lucency lateral to the carotid canal. The air-illed eustachian tube is inferior to the tensor tympani, and the TMJ is seen laterally.23,39 Coronal geniculate ganglion level (see Fig. 21-2B). CT: The tensor tympani muscle is seen along the medial wall of the middle ear, with the cochleariform process separating it from the eustachian tube below. The anteriormost part of the cochlea is medial to the tensor tympani. The geniculate ganglion is seen as a small lucency superior to the cochlea.23,39 MRI: The geniculate ganglion is seen as a punctate focus of intermediate signal on T1-weighted images.23,39 Coronal anterior tympanic level (see Fig. 21-2C). CT: The superior and inferior walls of the EAC are seen well. The TM may be identiied as a thin ilamentous structure extending from the scutum superiorly and coursing parallel to the plane of the long process of the malleus to attach to the limbus inferiorly. The head and neck of the malleus can be seen in the epitympanic space, with the tendon of the tensor tympani muscle attaching to neck. The basal and second turn of the cochlea are visualized. The labyrinthine and tympanic segments of the facial nerve are seen as two lucencies superior to the cochlea. The loor and roof (tegmen) of the middle ear are well visualized.23,39 MRI: The cochlea is of high signal on T2-weighted images. Coronal midtympanic level (see Fig. 21-2D and E). CT: This level shows the long process and lenticular process of the incus and the

incudostapedial articulation as an L-shaped coniguration. The stapes projects medially and superiorly from the lenticular process of the incus toward the oval window, located above the cochlear promontory. Prussak’s space is seen between the incus and scutum. The tympanic segment of the facial nerve canal is seen along the medial wall of the middle ear just superior and lateral to the cochlea.23,39 Coronal oval window level (see Figs. 21-2F, 21-6A and B). CT: The full extent of the IAC is well visualized at this level, with the central crista falciformis dividing the canal into two portions. On CT scans, the oval window is seen as a bony defect in the lateral portion of the vestibule. The stapes is oriented slightly superiorly toward the oval window, just inferior to the lateral SCC. Also, beneath the lateral SCC, the horizontal portion of the facial nerve canal appears as a small circular structure. The anterior limb of the superior SCC can be seen. The epitympanic space lies just lateral to the lateral SCC. The loor and roof (tegmen) of the middle ear are well visualized on CT scans.23,39 MRI: On T2-weighted images the facial and vestibulocochlear nerves can be seen as linear low-signal-intensity structures surrounded by the high-signal luid in the IAC. The inner ear structures are of high signal on T2-weighted images. On T1-weighted images the IAC and its contents are of intermediate signal.23,39 Coronal posterior tympanic level (see Fig. 21-2G). CT: The vestibule and round window niche are seen at this level. The sinus tympani—which extends between the labyrinthine wall and the pyramidal eminence—is seen, as is the facial nerve recess, which is lateral to the pyramidal eminence.23,39 Coronal jugular foramen level (see Fig. 21-2H). CT: The jugular foramen frequently has a dome-shaped outline. The mastoid segment of the facial nerve canal can be identiied lateral to the jugular foramen, running nearly vertical and extending toward the stylomastoid foramen. The mastoid antrum is seen superiorly and laterally. Portions of the lateral and superior SCCs can be seen.23,39 MRI: Variable signal can be seen in the jugular bulb within the jugular foramen, depending on the sequence, low, and presence of contrast. The mastoid segment of the facial nerve is seen as a linear intermediate signal structure lateral to the jugular bulb.23,39

Sagittal Images: Lateral to Medial Sagittal external auditory canal level (see Fig. 21-3A). CT: The EAC is seen in cross section just posterior to the TMJ. The relationship of the mandibular condyle to the glenoid fossa and EAC is well visualized.23 Sagittal descending facial nerve canal level (see Fig. 21-3B). CT: The descending facial nerve and posterior genu form an upsidedown hockey-stick shape. The head and manubrium of the malleus and the body and long process of the incus can be seen in a “molar tooth” coniguration. The lateralmost part of the lateral SCC is visualized.23 Sagittal vestibule level (see Fig. 21-3C). CT: The vestibule is seen as a central lucency. The common crus of the superior and posterior SCCs can be seen just posterior and superior to the vestibule. The round window is visualized, with the basal turn of the cochlea just anterior to the round window. The vestibular aqueduct appears as a thin linear structure underlying a lange of the posterior petrous bone.23 MRI: The vestibule and portions of the cochlea and SCCs are seen as areas of high signal on T2-weighted images. The contained endolymphatic duct and sac are seen as areas of high signal underlying a lange of the petrous bone.23

Sagittal internal auditory canal level (see Figs. 21-3D, 21-7). CT: The IAC is seen in cross section as an oval lucency. A portion of

CHAPTER 21 the cochlea can be seen anterior to the IAC. The carotid canal is anterior and the jugular fossa inferior to the otic capsule structures.23 MRI: MRI studies can demonstrate the individual nerves in the IAC, with the facial nerve superior and anterior, the cochlear nerve inferior and anterior, and the vestibular nerves posterior.23

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and must be assessed along with possible presence of a cholesteatoma. EAC atresia can be complete or stenotic.1 The EAC is considered narrowed if its diameter is less than 4 mm. Canal stenosis may be from a web or band of soft tissue, a bony plate at the level of the TM, or both.67 Many ossicular anomalies can occur with EAC maldevelopment. The ossicles may be fused, rotated, hypoplastic, or absent.1 The most common anomaly is fusion of the malleus and incus. The fused ossicles may also be fused to the atretic plate, usually at the region of the neck of malleus.112 The facial nerve canal must be carefully evaluated in all cases of suspected external and middle ear anomalies. Anomalous development of the middle ear and temporal bone may alter the course of the facial nerve, with the tympanic and mastoid segments most commonly affected. The tympanic segment is usually displaced inferiorly as low as the round window and may be medially displaced and cross the oval window. The mastoid segment is displaced anterolaterally and may exit the temporal bone at the level of the round window or into the TMJ1,67,83 (Fig. 21-8). Various grading systems and classiications have been developed for EAC atresia.47,86 The most common isolated congenital ossicular anomaly is incudostapedial discontinuity. In this anomaly the long process of the incus may be absent or it may be elongated and assume a more posterior trajectory than normal with respect to the oval window. Anomalies of the stapes suprastructure are often associated with abnormalities of the long process of the incus.112

Middle Ear and External Ear Malformations

Congenital Inner Ear Malformations

Congenital aural atresia is failure of development of the EAC. It is often associated with abnormalities of the auricle (microtia), ossicles, and middle ear. The inner ear is usually normal.27 The external ear, EAC, size of middle ear, ossicles, mastoid air cells, oval window, round window, and facial nerve course can potentially be dysplastic or absent

The different congenital inner ear malformations result from arrest during various stages of embryogenesis21,42,46,87 (Table 21-1). Michel’s deformity, or complete labyrinthine dysplasia, is absence of the inner ear structures. Cranial nerve VIII and its ganglion will be absent because the otic vesicle does not develop. The absence of cranial

Stenvers’ and Pöschl’s Views Stenvers’ view (see Fig. 21-4A-D). This plane is perpendicular to that of the superior SCC, which is seen in cross section, and parallel to that of the posterior SCC, which is well seen, as is the common crus. The turns of the cochlea are well seen on this view, as are the round window, descending facial nerve canal, and incudomalleolar joint. This view is perpendicular to the labyrinthine segment and parallels the tympanic segment of the facial nerve canal. It is also parallel to the tensor tympani muscle.23,54 Pöschl’s view (see Fig. 21-4E and F). This plane is parallel to the plane of the superior SCC, which can be seen throughout its course appearing as a ring, and the bone separating it from the middle cranial fossa is clearly deined. This plane is perpendicular to the posterior SCC. This plane is also perpendicular to the tympanic segment of the facial nerve canal, which is seen in cross section on this view. This plane is parallel to the plane of the axis (modiolus) of the cochlea and the labyrinthine segment of the facial nerve canal.23,54

A

B

FIG 21-8 EAC atresia. Newborn boy with unilateral ear deformity. Axial high-resolution multidetector CT image of the left temporal bone (A, superior; B, inferior) shows membranous and bony EAC atresia (long white arrow) and atretic middle ear cavity (short white arrow). Malleus and incus are rotated and dysplastic, with fusion at the incudomalleolar articulation and middle ear wall (long black arrow). Note aberrant inferolateral course of the facial nerve (short black arrow).

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nerve VIII results in decreased caliber of the IAC. Other associated anomalies include hypoplasia of the petrous bone, diminished volume of the mastoid and middle ear, lattening of the medial wall of the middle ear, and stapes aplasia or malformation.42,75,87 In cochlear aplasia, there is complete absence of the cochlea. The vestibule is present but often dysplastic. In cochlear hypoplasia, the cochlea and vestibule are separated but their dimensions are smaller than usual. The hypoplastic cochlea is seen as a small bud off of the IAC.42,87 Common cavity deformity is characterized by a single featureless labyrinthine cavity with no distinct vestibule, cochlea, or SCCs.42,87 Mondini’s malformation, more recently classiied as incomplete partition (IP) type II by Sennaroglu, has a cochlea with 1.5 turns. The middle and apical turns of the cochlea fuse to form one cavity owing to an interscalar defect. Dilatation of the vestibular aqueduct and vestibule are frequent associated anomalies42,87,107 (Fig. 21-9). The IP type 1 deformity (pseudo-Mondini’s or cystic vestibulocochlear malformation) consists of a cystic-appearing cochlea without a modiolus and a dilated vestibule without any internal structure. This is not associated with an enlarged vestibular aqueduct. IP type I is thought to result from an insult at an earlier stage of development than IP type II.87

TABLE 21-1

Congenital Malformations of

the Inner Ear Week of Gestation

Malformation

3 Late 3 4 5 6 7

Michel deformity Cochlear aplasia Common cavity Incomplete partition type I Cochlear hypoplasia Incomplete partition type II

A

Partition defects more subtle than those seen in Mondini’s malformation have also been described, consisting of modiolar and interscalar defects, often in association with an enlarged vestibular aqueduct.55 Enlarged vestibular aqueduct is a common cause of progressive hearing loss in children, with sudden exacerbations often occurring after minor trauma or illness. In 90% of cases, this malformation is bilateral. The aqueduct is considered dilated if it is larger than the diameter of an SCC or more than 1.5 mm wide.67 The endolymphatic sac within the aqueduct may or may not be proportionately enlarged.112 Many of these patients have cochlear abnormalities.55 The superior SCC is the irst of the SCCs to form, and the lateral SCC is the last to form. In most cases, only the lateral SCC can have isolated anomalous development; the two important exceptions to this rule occur in Waardenburg’s and Alagille’s syndromes, where there is isolated absence of the posterior SCC.42 CT evaluation of congenital inner ear malformations should include evaluation of the cochlear and vestibular aqueducts. In patients with large cochlear aqueducts, there is a high incidence of CSF leaks near the oval window (stapes gusher). Gushing occurs because the absence of bone at the base of cochlea allows for communication between the CSF in the IAC and perilymph. Preoperative recognition of this entity plays an important role in identifying patients at risk for perilymphatic stapes gushing and avoids worsening of sensorineural hearing loss.53 Cochlear implants have become a promising treatment option for children with sensorineural hearing loss. Before placement of cochlear implants, patients are studied with CT and MRI to characterize the inner ear anomalies. CT is superior to study the bony structures for surgical planning, whereas MRI can conirm that the space within the bony otic capsule is illed with luid and allows evaluation of the vestibulocochlear nerve.107

Semicircular Canal Dehiscence Syndrome. SCC dehiscence syndrome results from absence of the osseous covering of an SCC, usually

B FIG 21-9 Incomplete partition type II or Mondini’s malformation. A and B, Axial high-resolution multidetector CT images of temporal bones show an incomplete partition of the cochlea, with normal basal turn and cystic apices, with 1.5 turns (black arrows). Dilatation of the vestibule (long white arrows) and the vestibular aqueduct is also seen (short white arrows).

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B FIG 21-10 Superior semicircular canal dehiscence. Coronal oblique high-resolution multidetector CT image of the right (A) and left (B) temporal bones shows an absence of osseous covering overlying superior SCC on the left (arrow). Note normal osseous covering on the right (A).

the superior SCC. The dehiscence creates a “third window” in the labyrinth in addition to the oval and round windows.63 It is unclear whether this dehiscence is congenital or acquired.69 The abnormal connection between the middle cranial fossa and SCC results in abnormal vestibular function that may be provoked by sound (Tullilo’s syndrome) or changes in intracranial pressure. SCC dehiscence is seen as absence of bone overlying an SCC on CT or absence of overlying low signal from cortical bone on thin-section heavily T2-weighted MRIs16 (Fig. 21-10). Browaeys et al. have suggested using MRI with heavily T2-weighted images as a screening test in patients with vestibulocochlear symptoms, because in their study MRI had a sensitivity and negative predictive value of 100% for SCC dehiscence. Only patients with positive indings on MRI should undergo subsequent evaluation with CT; false positives can occur with MRI.16

Vascular Anomalies It is important to be aware of vascular anomalies to prevent vascular injury during surgery or mistakenly characterizing them as some other pathology. Agenesis of the petrous internal carotid artery can be mistaken for internal carotid artery occlusion. The carotid canal will not develop in cases of agenesis of the carotid artery. On CT the absence of the carotid canal and carotid sulcus is the clue that distinguishes agenesis of the petrous carotid artery from carotid artery occlusion. The internal carotid artery can have an aberrant course within the middle ear cavity.61 An intratympanic internal carotid artery is thought to occur from involution of a segment of the internal carotid artery during development. The actual intratympanic segment may be a collateral branch that occurs from the anastomoses of the inferior tympanic branch of the ascending pharyngeal artery (from the external carotid artery) with the caroticotympanic artery of the internal carotid artery. This aberrant course of the artery may be asymptomatic, but it can cause pulsatile tinnitus or conductive hearing loss if the artery is close enough to the ossicles. This anomaly may be confused with a middle ear mass such as a glomus tympanicum or hemangioma. Awareness of this entity and its imaging indings is important because it can prevent it from being biopsied or resected. On CT the carotid artery will bulge into the hypotympanum owing to dehiscence of the bony wall of the carotid canal. Other CT indings include absence of the vertical carotid canal and reduced caliber of the aberrant internal carotid artery as it passes through an enlarged inferior tympanic canal. On CT angiogram or MR angiogram, the intratympanic carotid artery will be located more posterior and lateral than normal and appear hypoplastic.13,61

Another type of intratympanic vascular anomaly is a persistent stapedial artery. The stapedial artery normally exists only during embryogenesis. If the artery does not regress, the middle meningeal artery does not develop. The persistent stapedial artery will then supply the structures normally supplied by the middle meningeal artery.88 Because the persistent stapedial artery originates from the petrous internal carotid artery, this implies an internal carotid artery route to the usual middle meningeal artery territory instead of an external carotid artery route. After branching from the petrous internal carotid artery, the persistent stapedial artery runs with the facial nerve through the tympanic cavity and then exits into the middle cranial fossa to supply the structures normally supplied by the middle meningeal artery. A persistent stapedial artery may be asymptomatic but may also cause tinnitus. It is important to be aware of persistent stapedial artery in patients undergoing stapes surgery, because the artery courses through the obturator foramen of the stapes and may be injured. Clues to an intratympanic course of the stapedial artery are a small canaliculus leaving the carotid canal, a linear structure crossing the middle ear over the promontory, enlargement of the tympanic portion of the facial nerve canal, or a separate canal parallel to the facial nerve and absence of the ipsilateral foramen spinosum. The foramen spinosum will be absent owing to absence of the middle meningeal artery that normally courses within it97 (Fig. 21-11). Anomalies of the jugular vein and bulb are common. A high-riding jugular bulb is a bulb present at the level of the IAC or cochlea. By itself it is of no clinical signiicance. However, if there is also dehiscence of the bony plate separating the jugular bulb from the hypotympanum, the high jugular bulb can then protrude into the middle ear and cause pulsatile tinnitus (Fig. 21-12). A jugular bulb diverticulum appears as an outpouching of the jugular bulb posterior to the IAC (Fig. 21-13).11 It is important to be aware of this benign entity to prevent mistaking it for a tumor. On MRI, slow low in a diverticulum may mimic a mass.

Inlammatory Lesions Both CT and MRI are important in identifying the primary changes and complications of temporal bone inlammatory disease. CT is useful for detecting bony erosions and soft tissue masses associated with middle ear inlammatory disease. Contrast-enhanced MRI studies can be used to show enhancing granulation tissue.

Acute Otomastoiditis. Acute otomastoiditis appears as middle ear and mastoid air cell opaciication with luid and nonspeciic debris. The luid in serous otitis media cannot be distinguished from the pus seen with purulent otitis. Subacute otitis media shows similar indings

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PART II CT and MR Imaging of the Whole Body

B

A

C FIG 21-11 Persistent stapedial artery. Axial high-resolution multidetector CT image of the right (A, B) and left (C) temporal bones shows persistent stapedial artery contained in an osseous covering originating from the petrous internal carotid artery, crossing the middle ear over the promontory (white arrows). Note absence of the right foramen spinosum and normal left foramen spinosum (black arrow).

in the mastoid air cells and middle ear, with the additional inding of focal or diffuse mucosal thickening. Spread of infection to the bone with erosion of the mastoid septae, lateral mastoid cortex, or cortex over the sigmoid plate is termed coalescent mastoiditis. High-resolution CT is the optimal imaging modality to assess for evidence of bone erosion94 (Fig. 21-14). MRI is mostly helpful for detecting suspected complications such as epidural abscess, subdural empyema, petrous apicitis, or thrombosis of the sigmoid sinus.103

Chronic Otomastoiditis. Chronic otomastoiditis follows repeated bouts of otitis media. It results in nonspeciic opaciication of the middle ear and mastoid air cells by granulation tissue and effusion.50 Reactive sclerosis results in thickening of the bony septa of the mastoid. If chronic otomastoiditis occurs during maturation of the mastoid during childhood, there will be a gradual reduction in the number of mastoid air cells, resulting in poorly developed mastoids. Chronic suppurative otitis media may occur in isolation or have an associated

CHAPTER 21

631

Temporal Bone A

*

FIG 21-14 Otomastoiditis and subperiosteal abscess. Axial highFIG 21-12 High-riding jugular bulb. Axial high-resolution multidetector CT image of the right temporal bone shows a high-riding jugular bulb with thinning of the sigmoid plate (arrow).

resolution multidetector CT image of the left temporal bone shows luid in the middle ear cavity and mastoid air cells, with osseous erosion (arrows) and associated left postauricular soft tissue mass (*).

A

A

B FIG 21-13 Jugular bulb diverticulum. Axial (A) and coronal (B) high-resolution multidetector CT image of the right temporal bone shows an outpouching of the jugular bulb posterior to the right internal auditory canal (arrows).

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PART II CT and MR Imaging of the Whole Body

FIG 21-15 Tympanosclerosis in a 45-year-old man with bilateral chronic otitis media and conductive hearing loss. Axial high-resolution multidetector CT image of the left temporal bone shows lack of visualization of normal ossicular articulations, with an osseous mass (black arrow) and thickened, retracted tympanic membrane (white arrow).

cholesteatoma or middle ear cholesterol granuloma. Ossicular erosions can occur with chronic otomastoiditis even in the absence of a cholesteatoma, most likely related to the action of osteoclasts and histiocytes.94 Conductive hearing loss can occur from chronic middle ear infection secondary to postinlammatory ossicular ixation. The ixation may be due to ibrous tissue, hyalinization of cartilage, or new bone formation. Fibrous tissue will appear as soft tissue density around the ossicles. Hyalinization of cartilage (tympanosclerosis) will appear as punctate, nodular, or weblike calciications in the middle ear, often involving ossicular tendons or ligaments (Fig. 21-15). If the calciications occur in the oval window, they can mimic fenestral otosclerosis. New bone formation will be apparent as dense bone in the epitympanum.94

Petrous Apicitis. Petrous apicitis is an infectious osteitis resulting most often from adjacent spread of otomastoiditis, usually in the setting of a pneumatized petrous apex. Cranial nerves V and VI course close to the petrous apex, separated from the bone by dura. The osteitis may cause Gradenigo’s syndrome, which manifests as facial pain or diplopia due to secondary inlammation of the adjacent cranial nerves. CT indings of petrous apicitis include opaciication of a pneumatized petrous apex and bone destruction (Fig. 21-16A and B). On MRI the petrous apex is opaciied and enhances (see Fig. 21-16C-E). MRI may also show enhancement of cranial nerves V and VI, Meckel’s cave, and dura adjacent to the petrous apex and cavernous sinus.38,80

Cholesteatoma. A cholesteatoma is a conglomerate mass of reactive cells involved in a localized chronic inlammatory process. Cholestea-

tomas are lined by stratiied keratinizing squamous epithelium with subepithelial ibroconnective or granulation tissue and keratin debris.106 Cholesteatomas are often clinically problematic because of their growth over time, the osseous erosions they cause, and their tendency to recur after resection. Most cholesteatomas are intratympanic.50 Very rarely they may occur in the EAC, mastoid, or petrous apex. The vast majority (98%) of cholesteatomas in the middle ear are acquired. A variety of theories have been proposed to explain the development of acquired cholesteatomas, which are beyond the scope of this chapter. Acquired cholesteatomas can be classiied as primary acquired and secondary acquired lesions. Primary acquired cholesteatomas (80% of all cholesteatomas) result from chronic infection with development of granulation tissue behind an apparently intact TM, usually in the region of the pars laccida. Secondary acquired cholesteatomas (18% of all cholesteatomas) develop through a perforation in the TM, usually involving the pars tensa and less often the pars laccida.9 On CT, primary acquired cholesteatomas are usually seen as a rounded, expansile, soft tissue mass in Prussak’s space, with erosion of the scutum and medial displacement of the ossicles. Secondary acquired cholesteatomas are often located in the facial recess and sinus tympani. Osseous erosion by a cholesteatoma may additionally lead to facial nerve canal dehiscence, labyrinthine istulas (usually affecting the lateral SCC), and dehiscence of the tegmen tympani with or without meningoencephalocele formation50,78,104 (Fig. 21-17). Congenital cholesteatomas (2% of all cholesteatomas) develop from embryonic epithelial rests that can occur anywhere in the temporal bone, including the middle ear. In the middle ear, congenital cholesteatomas most frequently originate in the anterior superior quadrant of the middle ear at the eustachian tube oriice near the anterior tympanic ring.90 A small nodular mass is usually seen on CT (Fig. 21-18). Ossicular erosions are uncommon with anteriorly located lesions, but erosion of the facial nerve canal may occur.9 It is important to note on imaging whether a cholesteatoma occupies the sinus tympani or facial nerve recess of the middle ear cavity. The sinus tympani and facial nerve recess are blind spots during surgical resection of cholesteatomas and are the most common and second most common sites of recurrent cholesteatoma, respectively. With a traditional operating microscope, the surgeon can only visualize structures directly ahead. This straight-line view is what creates these blind pockets during surgery. If the surgeon is aware of a cholesteatoma in the sinus tympanic and facial nerve recess, the surgical approach may be altered to remove the cholesteatoma from these sites and prevent a source of recurrence.5,43 Differentiation of cholesteatoma from a chronic otitis media may be impossible on CT owing to similar appearance of the entities and lack of bony destruction with small cholesteatomas. Further complicating differentiation is the fact that cholesteatomas may or may not be accompanied by chronic otitis media. Standard MRI sequences cannot differentiate cholesteatomas from other inlammatory lesions. However, half-Fourier acquisition single-shot turbo-spin echo (HASTE) diffusion-weighted sequences have been shown to be helpful in detecting cholesteatomas larger than 5 mm. Cholesteatomas will appear hyperintense on diffusion-weighted imaging (DWI)4,44 (Fig. 21-19).

Malignant External Otitis. Malignant (necrotizing) external otitis is most often associated with a Pseudomonas infection in older diabetic patients or immunosuppressed patients. Clinically it will be apparent because of otalgia and pus in the EAC.84 The infection may affect just the soft tissues and cartilage. However, it can also lead to osteomyelitis of the adjacent temporal bone

CHAPTER 21

Temporal Bone

22

A

B

C FIG 21-16 Gradenigo’s syndrome in a 49-year-old woman with history of left otitis media. Axial highresolution multidetector CT image of the right (A) and left (B) temporal bones shows opaciied left mastoids, left middle ear cavity, and left petrous apex (white arrow in B). Axial T2-weighted MRI (C) demonstrates luid opaciication of the left petrous apex (white arrow in C), with enhancement (white arrow in E) on postcontrast T1-weighted image. Continued

633

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PART II CT and MR Imaging of the Whole Body

E

D

FIG 21-16, cont’d Note normal marrow signal in the right petrous apex (black arrow) and luid signal in left petrous apex (white arrow) on non–fat-saturated precontrast T1-weighted image (D).

P

A

P

B FIG 21-17 Cholesteatoma in a 43-year-old woman with left facial paralysis. Coronal high-resolution multidetector CT images (A and B) of the left temporal bone show marked thickening of the tympanic membrane, with a perforation in the superior half and calciications involving the lower half (white arrow). Abnormal soft tissue is seen within the middle ear, with eroded incus and stapes, and is contiguous with the dehiscent tympanic segment of the facial nerve (black arrow).

CHAPTER 21

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B FIG 21-18 Congenital cholesteatoma in a 12-year-old boy with left conductive hearing loss and a white mass on otoscopy. Axial (A) and coronal (B) high-resolution multidetector CT images of the left temporal bone show a small, well-circumscribed lobular mass (white arrows) within the posterior mesotympanum, with demineralization of the long process of the incus (black arrow).

structures or skull base, with resultant cranial nerve palsies. Cranial nerve VII is the most common nerve to be involved, owing to dehiscence of the facial nerve canal or infection spreading through the stylomastoid foramen or mastoid segment of the facial nerve.70 Cranial nerves IX, X, and XI will be affected if infection spreads to the jugular foramen, and cranial nerves V and VI will be affected if infection spreads to the petrous apex. The infection can often smolder in the skull base if inadequately treated. Patients who have resolution of canal symptoms may present with cranial nerve palsies of seemingly unknown cause if osteomyelitis is not suspected.18,76 CT indings in external otitis include soft tissue thickening of the EAC, enhancement of canal granulation tissue, and osseous erosions (Fig. 21-20). MRI is more useful to assess soft tissue spread of disease, skull base osteomyelitis, and cranial nerve palsies (Fig. 21-21).50,76

Labyrinthitis. Labyrinthitis is an inlammatory process of the perilymphatic space that results in changes in the endolymphatic space. It can result from infection, trauma, or autoimmune disease. MRI is sensitive to subtle changes of the membranous labyrinth in patients who present with sudden symptoms such as vertigo or hearing loss. The basal turn of the cochlea is most commonly affected. Acutely, inner ear enhancement is seen on MRI. Increased precontrast T1 signal can represent hemorrhage within the labyrinth.105 In the intermediate stage, ibrosis results in loss of luid signal in the affected inner ear structures on heavily T2-weighted MRI images. Labyrinthitis ossiicans is a late stage of labyrinthitis in which a cascade of inlammatory reactions results in ossiication with new bone formation.29 It is only in the late stage when the CT becomes abnormal with bony attenuation in the cochlea, vestibule, and/or SCCs29,50 (Fig. 21-22).

Bell’s Palsy. Bell’s palsy is the most common cause of acute facial paralysis. It is thought to be due to reactivation of a viral infection in the geniculate ganglion. On MRI there may be variable pathologic contrast enhancement of cranial nerve VII, but pathologic enhancement of the nerve is not speciic for Bell’s palsy; it can occur with other diseases. Normal areas of contrast enhancement along cranial nerve VII occur at the geniculate ganglion and the tympanic and mastoid segments, which is actually enhancement of the normal vascular plexus that surrounds these portions of the nerve. Enhancement is pathologic

when it occurs in the cisternal, meatal, labyrinthine, and extracranial (just beyond the stylomastoid foramen) segments of the nerve.32

Neoplastic Lesions Benign Neoplasms Osteomas and exostoses. Osteomas are rare benign tumors that are often incidentally found on CT imaging. They are commonly located at the tympanosquamous suture within the EAC but can also arise in the mastoid process and IAC.6,17,26 They are considered true neoplasms as opposed to exostoses, which are considered reactive periosteal bony growths, most commonly in response to prolonged cold water exposure. Radiographically, osteomas are unilateral and solitary pedunculated hyperdense masses on CT, whereas exostoses present as multiple sessile, bilateral, hyperdense masses (Fig. 21-23). Often these lesions are clinically asymptomatic and do not require surgery unless there is conductive hearing loss, recurrent EAC infections, or signiicant cerumen retention due to the signiicant surgical complications associated with their removal, including TM perforation, infection, ossicular disruption, and injuries to the TMJ and facial nerve.102 Even with surgical removal, signiicant exostoses often recur despite cessation of cold water exposure.99 Schwannomas. Schwannomas are benign tumors of the temporal bone typically arising along cranial nerves VII and VIII. Vestibular schwannomas (VS) are the most common IAC/CPA cistern tumor and the second most common extraaxial neoplasm in adults. Facial nerve schwannomas are rare.15 VS most commonly involve the inferior vestibular nerve and classically arise at the porus acusticus. VS should be considered in patients with symptoms of sensorineural hearing, tinnitus, disequilibrium, or facial nerve palsy, although they are often asymptomatic. MRI has better sensitivity for detecting these tumors than CT. Classic MR features of vestibular schwannomas include a cylindrically shaped (smaller size) or “ice cream cone”–shaped (larger size) mass with T2 hypointense signal and avid enhancement (Fig. 21-24). As they enlarge they can extend into the posterior fossa, causing mass effect on the brainstem or hydrocephalus. Typically the border of a VS extending into the CPA forms an acute angle with the temporal bone. The rate of growth can be slow; therefore long-term MR surveillance is appropriate.7

636

PART II CT and MR Imaging of the Whole Body

*

FD

L

L

5 cm 5 cm

A

B

C

D FIG 21-19 Recurrent cholesteatoma in a 27-year-old woman with skull base ibrous dysplasia (FD), status post right partial mastoidectomy. Axial high-resolution multidetector CT images of the right temporal bone (A, superior; B, inferior) show a soft tissue mass in the right mastoidectomy bed (* on A) with dehiscence of the lateral wall of the descending mastoid segment of the facial nerve (black arrow on B). Note that the external auditory canal is closed off owing to prior surgery (long white arrow), with a dysmorphic and eroded head of the malleus and portions of the incus (short white arrow). On DWI this mass was hyperintense on b-1000 imaging sequences (C, white arrow), with low ADC values (D, white arrows).

CHAPTER 21

637

Temporal Bone

*

L

* * A A

B FIG 21-20 External otitis. Axial (A) and coronal (B) high-resolution multidetector CT images of the left temporal bone show debris in the external auditory canal, with osseous erosion along the posterior external auditory canal (white arrow). Note the extensive swelling of the left ear and left periauricular soft tissues (*). Minimal tissue in Prussak’s space (black arrow), with partial opaciication of the mastoid air cells, without scutum erosion or conluent mastoiditis.

There are three distinct surgical approaches for VS every radiologist should know: the middle cranial fossa (MCF), suboccipital, and translabyrinthine approaches. The MCF approach is used for patients with good hearing and mainly intracanalicular lesions with less than 1 cm CPA extension, because it is the only technique that does not violate the inner ear structures. However, it has a slightly increased risk of facial nerve palsy. For lesions with greater CPA extension, the suboccipital approach is used and can preserve hearing function; however, it has limited access into the lateral IAC and is prone to CSF leaks. Finally, the translabyrinthine approach is reserved for patients who have lost hearing function, but it offers lowest recurrence rates.89 Facial nerve schwannomas can occur along the entire course of the facial nerve but most commonly involve the geniculate ganglion.109 The presenting symptoms can provide insight on the location of the schwannoma. For example, sensorineural hearing loss is caused by compression of cranial nerve VIII at the CPA, whereas conductive hearing loss is caused by ossicular chain dysfunction from tympanic cavity schwannomas. Classic MR features include a fusiform mass with T1 hypo- to isointense signal, T2 hyperintense signal, and avid enhancement along the facial nerve. Modern MR and CT techniques with thinner sections have recently shown a variety of appearances, including “dumbbell shape” in the CPA-IAC, multilobular morphology in the tympanic segment, and an “invasive” appearance in the mastoid segment.109 CT can evaluate for bony scalloping/remodeling involving the IAC and geniculate ganglion, which can distinguish facial from vestibular schwannomas (Fig. 21-25). If the tumor is proximal to the geniculate ganglion with preserved hearing and minimal CPA extension, the MCF approach is used. The suboccipital approach is used when there is more than 1-cm CPA extension. If hearing function is lost, the translabyrinthine approach is favored, given the direct access. Tympanic-segment schwannomas are reached via the transmastoid approach; mastoid-segment schwannomas may also require following the nerve into the parotid gland.109

Meningiomas. Meningiomas are a common intracranial neoplasm but rarely involve the temporal bone.37,98 Although histologically they arise from arachnoid caps cells like their intracranial counterparts, there is controversy regarding the exact origin.98 When they occur the common locations include the tegmen tympani, jugular foramen, and IAC. Identifying not only the location of the meningioma but spread of the tumor is important in the temporal bone. Jugular foramen and tegmen tympani meningiomas characteristically spread into the middle ear cavity, whereas IAC meningiomas spread into the intralabyrinthine structures. When in the middle ear cavity, they can encase the ossicular chain, resulting in conductive hearing loss. Middle ear cavity meningiomas can be distinguished from cholesteatomas by lack of bony erosions and enhancement and can be distinguished from glomus jugulare paragangliomas by permeative-sclerotic bony changes rather than permeative-destructive bony changes.37 Temporal bone meningiomas can present with a similar clinical presentation to other commonly found lesions; therefore differentiating imaging features can aid signiicantly in surgical planning. On CT, meningiomas can be iso- to hyperdense, with some containing calciication, but a majority exhibit avid uniform enhancement (Fig. 21-26A and B). On MRI, they can be iso- to hypointense on T1 and intermediate signal on T2. Marked T2 hyperintense signal and low voids are not typical. The classic “dural tail” enhancement is typically present, which distinguishes it from schwannoma (see Fig. 21-26C and D). The border between a meningioma in the CPA cistern and the temporal bone is usually an obtuse angle.37 Paragangliomas. Paragangliomas, also known as glomus tumors, are derived from neural crest paraganglion chief cells and develop throughout the body. They are classiied based on their location. Speciically, paragangliomas that develop along the jugular foramen wall are called glomus jugulare, and ones that develop along the tympanic plexus of Jacobsen’s nerve, a glossopharyngeal nerve branch, are called glomus tympanicum. They are the most common middle ear tumor

638

PART II CT and MR Imaging of the Whole Body

B

A

C FIG 21-21 Skull base osteomyelitis. A, Axial high-resolution multidetector CT image of the left temporal bone shows areas of cortical deiciency, with osseous erosion and destruction along the inner cortical table of the left temporal bone at the level of the mastoid and junction of the left sigmoid and distal transverse sinuses (long white arrows). B, Precontrast axial T1-weighted MRI shows marrow signal abnormality of the left skull base involving the left occipital bone, occipital condyle, and lateral clivus (white arrows). No gadolinium-based contrast agent was administered, because the patient was in renal failure. Opaciication of the left mastoid air cells is seen on axial CT image (short white arrow in A), as well as on axial T2-weighted MRI (C), along with osseous narrowing of the left external auditory canal (black arrow in A).

and second most common temporal bone tumor after vestibular schwannomas. MRI features include a mass with low to intermediate signal on T1-weighted and hyperintense signal on T2-weighted images. A mixed pattern with hyperintense and hypointense foci (“salt-andpepper appearance”) on T1- and T2-weighted images is often seen with paragangliomas, particularly larger lesions.73 Paragangliomas have avid enhancement. On CT there can be permeative-destructive bony changes, particularly at the jugular foramen, which distinguishes them from meningiomas. Glomus jugulare tumors characteristically cause dehiscence of the hypotympanum of the middle ear, whereas glomus tympanicum tumors usually arise on the cochlear promontory without bony destruction (Fig. 21-27). Most occur as a solitary lesion and are benign, but there are no reliable imaging features to identify malignant tumors unless metastatic lesions are present. MRI and digital subtraction angiography is used preoperatively to assess the collateral cerebral blood low and contralateral sigmoid sinus and internal jugular vein if the ipsilateral vessels will need to be sacriiced.72,100,101

Treatment options are controversial, with considerable debate in the literature; however, a consensus paper by Gjuric and Gleeson states patients with multifocal tumors must be assessed very carefully before surgical intervention owing to increased risk for profound neurologic deicits including laryngeal function and ability to swallow and hear.34 Epidermoids (epidermoid cysts). Epidermoid tumors, also known as cholesteatomas, are rare intracranial tumors, with about half occurring in the CPA cistern.85 They arise from ectodermal rests and have a thin, keratinized, stratiied squamous epithelium capsule. They are slow growing and nonneoplastic, but because the capsule can become densely adherent on adjacent neurovascular structures, surgical removal can be dificult. Aside from the CPA, they can occur in the EAC, middle ear cavity, and petrous apex. On MRI, they are hypointense on T1-weighted and hyperintense on T2-weighted images, making identiication and delineation of their extent dificult. On luid-attenuated inversion recovery (FLAIR) images they are usually heterogeneously hyperintense, allowing easier detection than on conventional MR sequences. However, the heterogeneous signal and

CHAPTER 21

A

Temporal Bone

B FIG 21-22 Labyrinthitis ossiicans. Axial (A) and coronal (B) high-resolution multidetector CT images of the right temporal bone shows bony attenuation in the cochlea (long white arrow in A; white arrow in B), vestibule (short white arrow in A) and semicircular canals (black arrow).

A

B FIG 21-23 External auditory canal exostoses in a 52-year-old man with chronic ear infections. Axial highresolution multidetector CT images of the right (A) and left (B) temporal bone show extensive external auditory canal exostoses (surfer’s ear), causing moderate to severe narrowing of the external auditory canals, right worse than left (arrows).

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FIG 21-24 Vestibular schwannoma. Axial postcontrast T1-weighted image shows bilateral vestibular schwannomas (arrows) in a patient with neuroibromatosis type 2.

A

adjacent CSF artifacts associated with intracranial epidermoids limit the ability of FLAIR images to deine the border of the mass. DWI is very sensitive in detecting epidermoids, which appear hyperintense on this sequence and of low signal on apparent diffusion coeficient (ADC) images.36 Constructive interference in the steady state (CISS) sequences may help delineate tumor extent and differentiate the mass form adjacent nerves and vessels. On CISS sequences, epidermoids are typically slightly hypointense and heterogeneous compared to CSF59 (Fig. 21-28). Typical CT features include a well-deined, lowattenuating, nonenhancing mass, but atypical features include high attenuation and partly calciied components.91 Miscellaneous benign lesions. Hemangiomas arise from the capillary bed of the epineurium and can cause compression or invasion of the nerve. In the temporal bone, they most commonly affect the geniculate ganglion but can also occur in the IAC.60 On CT they have been described as having a “honeycomb” high-density matrix due to small spicules of calcium, with enlargement of the facial nerve canal. Partial calciication can be helpful to distinguish facial nerve hemangiomas from facial nerve schwannomas.24 On MRI they are usually isointense on T1-weighted and hyperintense on T2-weighted images relative to gray matter, with small foci of low signal on both sequences, likely related to calciication. There is signiicant enhancement after contrast administration.111 There is often extension into the temporal bone beyond the facial nerve canal24 (Fig. 21-29). As with the vestibular nerve, schwannomas can also occur in the vicinity of the temporal bone from the other cranial nerves, including cranial nerves V, IX, X, XI, and XII. Lower cranial nerve lesions within the jugular foramen can mimic paragangliomas but are less vascular.31 Lipomas can also occur, usually within the IAC. Typical features include T1 hyperintense signal without enhancement (Fig. 21-30). Fat saturation techniques are helpful to conirm the diagnosis.25 Arachnoid cysts, particularly in the CPA cistern, can mimic epidermoid cysts. These are nonneoplastic intraarachnoid lesions containing normal CSF. Their attenuation and signal characteristics on CT and MRI, respectively, follow CSF characteristics. They are distinguished from epidermoids, given lack of high signal on DWI. Rarely dermoid cysts or neuroenteric cysts can occur in the CPA.12 Cholesterol granulomas can occur in the temporal bone, usually in the middle ear and mastoid air cells and less commonly in the petrous apex. They characteristically are expansile with hyperintense signal on T1- and T2-weighted images (Fig. 21-31). Although there are two competing theories regarding their pathogenesis, they are slowgrowing collections and are nonneoplastic. When they occur in the petrous apex, they must be distinguished from other diseases processes, including effusion, cholesteatoma, trapped luid (“leave-me-alone lesion”), petrous apicitis, mucocele, cephalocele, and malignant tumors.2,52,66,77,92

Malignant Neoplasms. Primary malignant neoplasms of the tem-

B FIG 21-25 Presumed facial nerve schwannoma in a patient with longstanding abnormal left facial movements. A, Axial CT through temporal bones shows fusiform expansion of the left anterior genu (arrow). B, Axial postcontrast T1-weighted image shows an avidly enhancing mass in the left internal auditory canal, extending to the left fallopian canal and geniculate ganglion of the left facial nerve (arrow). Note the normal right side for comparison.

poral bone are relatively uncommon; the most common are squamous or basal cell carcinoma, which most commonly involve the EAC or mastoid region. They are aggressive when they occur, often extending to the EAC, middle ear cavity, or mastoid air cells, with involvement of the facial nerve and TMJ.57 Distant metastases are rare for these tumors.22 Adenocarcinoma can present locally with similar features as squamous cell carcinoma, but lymph node involvement is more common. Chondrosarcomas and less commonly chordomas involve the petrous apex, generally arising along the petrosphenoidal and petrooccipital synchondroses.74 Endolymphatic sac tumors are low-grade slow-growing papillary cystadenomatous tumors that usually present along the retrolabyrinthine petrous bone around the

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D FIG 21-26 Meningioma. A, Axial CT image at the level of the temporal bones shows a large, partially calciied extraaxial mass in the left CPA cistern (*). B, Note normal appearance of the left IAC (arrow) on axial bone window image. On MRI there is avid postcontrast enhancement (*) on axial (C) and coronal (D) postcontrast T1-weighted images, with presence of “dural tail” (arrow).

GT

*

FIG 21-27 Glomus tympanicum. Axial high-resolution multidetector CT image of the left temporal bone shows a soft tissue mass (GT) at the cochlear promontory (*).

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D FIG 21-28 CPA epidermoid cyst. A, Axial CT shows a CSF attenuation lesion in the left CPA cistern (arrow). On MRI it is bright on heavily T2-weighted sequence (B), with no postcontrast enhancement (C). D, Note characteristic diffusion restriction on b-1000 images.

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B FIG 21-29 Presumed left facial nerve hemangioma in a patient with progressive left facial paralysis. A, Axial high-resolution multidetector CT image of the left temporal bone shows a mixed lytic and sclerotic lesion involving the left fallopian canal and left anterior genu of the facial nerve (long white arrow). Soft tissue from this lesion extends into the middle ear cavity, with dehiscence of the tegmen tympani (short white arrow). B, Intense enhancement of mass (white arrow) is seen on postcontrast axial T1-weighted image.

vestibular aqueduct.8,68 In children the most common primary malignant tumor in the middle ear cavity is embryonal rhabdomyosarcoma. This is a highly aggressive tumor that spreads with bone destruction, early involvement of the facial nerve, and intracranial spread.51 CT and MRI are considered complementary imaging techniques for evaluation of temporal bone malignancies, with CT being highly sensitive in detecting bone erosion, while MRI can delineate the tumor extent and differentiate tumor from nonneoplastic soft tissue.33,65 Malignant tumors can also locally spread into the temporal bone. The most common pathways of extension include nasopharyngeal carcinomas and salivary gland tumors via the eustachian tube and EAC or squamous cell carcinoma and adenoid cystic carcinoma via perineural spread along the skull base cranial nerves. The facial nerve is the most commonly involved nerve for perineural spread71 (Fig. 21-32). Metastases of the temporal bone are not uncommon and can spread hematogenously from the breast, lung, stomach, prostate gland, or kidney. Malignant tumors can mimic meningiomas or paragangliomas, given the permeative bony changes and enhancement.

Traumatic Injuries (Fractures) The classic way to categorize a temporal bone fracture is by the direction it courses relative to the petrous portion of the temporal bone. Longitudinal temporal bone fractures course parallel to the long axis of the petrous pyramid, whereas transverse fractures course perpendicular to the long axis of the petrous pyramid. Fractures of the temporal bone can be complex, with both longitudinal and transverse components96 (Fig. 21-33). Alternative classiications have been

proposed because the prognostic value of the traditional classiication has been questioned. These newer classiication systems include otic capsule sparing versus otic capsule violating and petrous versus nonpetrous involvement.45,58,79 Longitudinal fractures typically extend from the temporal squamosa across the roof or posterior wall of the EAC into the tympanic cavity and tegmen tympani toward the petrous apex. These often involve the ossicular chain and facial nerve near the anterior genu. Conductive hearing loss is a possible complication of longitudinal fracture if it results in ossicular dislocation or hemotympanum. Facial nerve paralysis occurs in about 20% of patients. There may be extension to the carotid canal with vascular injury. These comprise 70% to 90% of temporal bone fractures.96 Transverse fractures typically extend from the jugular foramen and foramen magnum to the middle cranial fossa. These fractures often extend through the vestibular aqueduct, otic capsule, and IAC near the fundus. Sensorineural hearing loss can occur if there is disruption of the otic capsule around the membranous labyrinth.96 Facial nerve paralysis occurs more often with transverse fractures than longitudinal fractures. It can occur either due to disruption of the facial nerve canal or facial nerve edema from contusion. If there is immediate facial nerve paralysis after a fracture, it is usually due to disruption of the nerve. If there is delayed facial nerve paralysis, it is often due to nerve edema or subtotal injury.110 Pneumolabyrinth is the presence of air in the normally luid-illed labyrinth. In the presence of trauma, pneumolabyrinth implies an otic capsule disruption with communication between the luid-illed inner ear and the air-illed middle ear cavity35 (Fig. 21-34). However, air in

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C FIG 21-30 Facial nerve lipoma. Incidental detection of focal fat in the distal mastoid segment of the left facial nerve (arrows), bright on T1- (A) and T2-weighted (B) images, with signal dropout on DWI (C) in a patient being evaluated for dizziness. Note that all commercial diffusion-weighted sequences use some sort of fat suppression to suppress chemical shift artifacts.

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C FIG 21-31 Cholesterol granuloma in a 65-year-old woman with left-sided aural fullness and vertigo. A, Axial high-resolution multidetector CT image of the left temporal bone shows well-corticated expansile lesion of the left petrous bone (white arrow). On MRI, this lesion is mildly hyperintense on T1-weighted imaging (B), without pathologic enhancement (C) (white arrow). Note the tip of the petrous apex is marrow containing (black arrow on A).

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C FIG 21-32 An 80-year-old man with remote history of parotid adenocarcinoma presenting with new left facial paralysis. A, Axial precontrast T1-weighted image shows a spiculated mass in the parotidectomy bed (arrow). Axial (B) and coronal (C) postcontrast fat-suppressed T1-weighted images demonstrate thickening and enhancement of the entire course of the left facial nerve involving the mastoid portion, proximal and distal tympanic segments, geniculate ganglion, and labyrinthine portion, illing the internal auditory canal (arrows) and consistent with perineural spread of neoplasm.

cc JF

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* *

B FIG 21-33 Complex temporal bone fracture in a 26-year-old male trauma patient. A, Axial high-resolution multidetector CT image of the left temporal bone shows comminuted oblique fracture involving the left mastoid and petrous segments, left jugular foramen (JF), and left carotid canal (CC). Partial opaciication of the left mastoid air cells and middle ear cavity (*) from posttraumatic hemorrhage. Gas locules and hypodensity seen along the course of the left transverse and sigmoid sinuses (arrows). B, Axial source images from a CT angiogram demonstrate venous thrombosis of the left transverse and sigmoid sinuses (arrows), extending to the proximal left internal jugular vein (not shown).

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the labyrinth or cochlea is not speciic for trauma, because it can also result from a spontaneous inner ear–middle ear istula.

Metabolic and Dysplastic Lesions The petrous temporal bone may be affected by a variety of primary bone diseases that can involve other portions of the skeleton. When they involve the temporal bone, the signiicance is related to disturbances of hearing, balance, or facial nerve function.

Otosclerosis. Otosclerosis is a hereditary osteodystrophy of the otic capsule that results in hearing loss. In the majority of cases the bilateral otic capsules are affected. Pathologically, otosclerosis consists of an active phase of resorption (otospongiosis) and an inactive phase of immature bone deposition (sclerosis). Otosclerosis can affect any part of the otic capsule. The most common types of otosclerosis are fenestral and cochlear. Fenestral otosclerosis, which involves the oval window and stapes footplate, causes conductive hearing loss. Cochlear otosclerosis, which involves the labyrinthine capsule or cochlea, will cause progressive sensorineural hearing loss.82 Fenestral otosclerosis most commonly begins in the area of the issula ante fenestram of the oval window82 (Fig. 21-35). It can spread across the stapedial annular ligament to ix the stapes footplate.14 On CT, early fenestral otosclerosis appears as small lucencies within the otic capsule at the anterior margin of the oval window. Later, otosclerotic foci may cover the oval window, stapes, and round window.93

FIG 21-34 Pneumolabyrinth in a trauma patient. Axial high-resolution multidetector CT image of the right temporal bone shows small foci of air within the vestibule (black arrow) and cochlea (white arrow). There was a nondisplaced occipital bone fracture and bifrontal parenchymal contusions (not shown), but no temporal bone fracture or ossicular disruption was identiied.

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B FIG 21-35 Fenestral otosclerosis in a 42-year-old man with moderately severe mixed hearing loss in the left ear. Axial high-resolution multidetector CT images of the right (A) and left (B) temporal bones show focal area of demineralization anterior to the left oval window (arrow in B). The right side is normal.

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On CT, cochlear otosclerosis appears as a crescentic hypodense rim paralleling the margins of the basal turn of the cochlea, the entire cochlea, or the whole otic capsule. Other patients may have areas of sclerosis. T1-weighted MRI reveals fuzzy soft tissue signal intensities in the cochlear capsule. Contrast enhancement may be seen, which is presumably due to contrast medium pooling in the numerous blood vessels of the otospongiotic foci.28,93 Cavitary otosclerosis, a rare form of otosclerosis, appears as hypodense foci in the anterior wall of the IAC.14 Most patients with otosclerosis are treated with stapedectomy and prosthetic implants. Recurrent hearing loss after prosthetic implants may be due to migration or dislocation of the implant or necrosis/ erosion of the ossicular attachment of the implant.108

Other. A variety of other metabolic and dysplastic disorders can involve the temporal bone, including osteogenesis imperfecta, Paget’s disease, ibrous dysplasia, and osteopetrosis.3,30,40,49

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95. Swartz JD, Harnsberger HR: Imaging of the temporal bone, 3rd ed, New York, 1998, Thieme, pp 240–317. 96. Swartz JD, Kang MD: Trauma to the temporal bone. In Som PM, Curtin HD, editors: Head and neck imaging, 5th ed, St. Louis, 2011, Elsevier Mosby, pp 1167–1181. 97. Thiers FA, Sakai O, Poe DS, et al: Persistent stapedial artery: CT indings. AJNR Am J Neuroradiol 21:1551–1554, 2000. 98. Thompson L, Bouffard J, Sandberg G, et al: Primary ear and temporal bone meningiomas: A clinicopathologic study of 36 cases with a review of the literature. Mod Pathol 16:236–245, 2003. 99. Timofeev I: Exostoses of the external auditory canal: A long term follow-up study of surgical treatment. Clin Otolaryngol Allied Sci 29:588–594, 2004. 100. van den Berg R: Imaging and management of head and neck paragangliomas. Eur Radiol 15:1310–1318, 2005. 101. van den Berg R, Schepers A, de Bruine FT, et al: The value of MR angiography techniques in the detection of head and neck paragangliomas. Eur J Radiol 52:240–245, 2004. 102. Vasama J: Surgery for external auditory canal exostoses: A report of 182 operations. J Otol Rhinol Laryngol 65:189–192, 2003. 103. Vazquez E, Castellote A, Piqueras J, et al: Imaging of complications of acute mastoiditis in children. Radiographics 23:359–372, 2003. 104. Vikram B, Udayashankar S, Naseeruddin K, et al: Complications in primary and secondary acquired cholesteatoma: A prospective comparative study of 62 ears. Am J Otolaryngol 29:1–6, 2008. 105. Weissman JL, Curtain HD, Hirsch BE, et al: High signal from the otic labyrinth on unenhanced magnetic resonance imaging. AJNR Am J Neuroradiol 13:1183–1187, 1992.

106. Wenig BW: Non-neoplastic lesions/disease of the ear and temporal bone. In Atlas of head and neck pathology, Philadelphia, 2008, Saunders Elsevier, pp 719–759. 107. Westerhof JP, Rademaker J, Weber BP, et al: Congenital malformations of the inner ear and the vestibulocochlear nerve in children with sensorineural hearing loss: Evaluation with CT and MRI. J Comput Assist Tomogr 25:719–726, 2001. 108. Whetstone J, Nguyen A, Nguyen-Huynh A, et al: Surgical and clinical conirmation of temporal bone CT indings in patients with otosclerosis with failed stapes surgery. AJNR Am J Neuroradiol 35:1195–2011, 2014. 109. Wiggins RH, 3rd, Harnsberger HR, Salzman KL, et al: The many faces of facial nerve schwannoma. AJNR Am J Neuroradiol 27:694–699, 2006. 110. Woodson EA, Smith RJH: Bilateral pneumolabyrinth diagnostic for otic capsule fractures without high-resolution imaging. Otolaryngol Head Neck Surg 137:969–971, 2007. 111. Yue Y, Jin Y, Yang B, et al: Retrospective case series of the imaging indings of facial nerve haemangioma. Eur Arch Otorhinolaryngol 2014 272:2497–2503, 2015. 112. Yuen HY, Ahuja AT, Wong KT, et al: Computed tomography of common congenital lesions of the temporal bone. Clin Radiol 58:687–693, 2003. 113. Zhen J, Liu C, Wang S, et al: The thin section anatomy of the temporal bone correlated with multislice spiral CT. Surg Radiol Anat 29:409–418, 2007.

22 Pharynx Suyash Mohan, Supreeta Arya, Tushar Chandra, and Ellen Hoeffner

INTRODUCTION The pharynx is a ibromuscular tube situated directly anterior to the vertebral column. It extends from the skull base to the lower border of the cricoid cartilage. It comprises a group of six muscles that are predominantly responsible for the voluntary act of swallowing: three pharyngeal constrictor muscles (superior, middle, and inferior constrictor muscles) and three vertically oriented muscles (stylopharyngeus, salpingopharyngeus, and palatopharyngeus). They are innervated by the pharyngeal branch of the vagus nerve (cranial nerve [CN] X), with the exception of the stylopharyngeus muscle, which is innervated by the glossopharyngeal nerve (CN IX). Based on the location, the pharynx is often subdivided into the following three sections: • Nasopharynx: top of the pharynx, located behind the nasal cavity and extends from the skull base to the soft palate • Oropharynx: located behind the oral cavity and extends from the uvula to the hyoid bone • Hypopharynx: extends from the hyoid bone to the cricopharyngeus muscle, located at C5-C6 level, at the lower end of the cricoid cartilage

IMAGING RATIONALE AND TECHNIQUES Computed tomography (CT) and magnetic resonance imaging (MRI) are currently the primary modalities for investigating pathologies of the pharynx. Although the supericial extent of mucosal lesions can be readily identiied by the examining physician, their deep submucosal extent is almost totally inaccessible to clinical or endoscopic evaluation. CT offers rapid image acquisition and is helpful in the acute setting for rapidity of acute diagnosis. In particular the high spatial resolution of CT can provide precise anatomic detail. MRI on the other hand offers beneits over CT because of its higher soft tissue contrast resolution, multiplanar capability, and superiority in detecting perineural tumor spread and intracranial invasion. The role of advanced biological imaging techniques such as MR spectroscopy, MRI diffusion and perfusion, CT perfusion, and luorodeoxyglucose positron emission tomography (FDG-PET) is discussed toward the end of this chapter.

NASOPHARYNX Anatomy The nasopharynx is the superiormost portion of the pharynx, located immediately below the skull base. It is attached to the undersurface of the clivus by the pharyngobasilar fascia of the superior constrictor muscle. The posterior and lateral walls of the nasopharynx are in

continuity with the posterior and lateral oropharyngeal walls, respectively, and it is inferiorly limited by the soft palate. Along the lateral nasopharyngeal wall there are two indentations and one protrusion into the lumen. The indentations (recesses) are the eustachian tube oriice and the lateral pharyngeal recess (often known by its eponym, the fossa of Rosenmüller), whereas the protrusion is the torus tubarius (the cartilaginous portion of the eustachian tube). On axial images, the lateral pharyngeal recess is located posterior to the torus tubarius, and it is superior to the torus tubarius on coronal images (Fig. 22-1A-B). The posterior pharyngeal wall has an undulating contour from the prevertebral longus capitis muscles, which demarcates the posteromedial aspect of the lateral pharyngeal recess. There is a small lateral hiatus or opening in the skull base attachment known as the foramen of Morgagni through which the eustachian (pharyngotympanic) tube and levator veli palatini muscle pass (see Fig. 22-1C-D). The levator veli palatini and the tensor veli palatini muscles are identiiable on T1-weighted MRI scans in the lateral wall of the nasopharynx and are responsible for opening the eustachian tube and for tensing and elevating the palate to prevent oronasal relux. The eustachian tube communicates with the middle ear, allowing both middle ear aeration and drainage. The foramen of Morgagni is an essential anatomic structure but is also a potential weak spot through which nasopharyngeal neoplasms or infections may spread directly to the skull base or laterally to the parapharyngeal fat.

Congenital Lesions Thornwaldt’s Cyst. Thornwaldt’s cyst, named after German physician Gustav Ludwig Thornwaldt, is a common developmental benign midline nasopharyngeal mucosal cyst. It is usually asymptomatic and is detected incidentally on imaging. Peak incidence has been variably reported between the ages of 15 and 60 years. It has an autopsy prevalence of approximately 4%, with no gender predilection. It results from focal adhesion of pharyngeal mucosa to the notochord (a midline collection of cells that aids embryonic long-axis and neural plate development), which is then carried up as the notochord ascends to the developing skull base. This creates a potential space known as the pharyngeal bursa, whose oriice becomes obliterated after an attack of pharyngitis, thereby forming the cyst. A Thornwaldt’s cyst lacks osseous involvement and corresponds to a superior level in the clivus. These are almost always asymptomatic; however, if they become infected the patient presents with persistent or periodic nasopharyngeal drainage, halitosis, and foul taste. Some may present with otitis media due to obstruction of the eustachian tube. Dull occipital headache has also been described. A symptomatic cyst is also called Thornwaldt’s disease.68 Thornwaldt’s cyst appears as a well-circumscribed, thin-walled, midline (but may be slightly paramidline) posterior nasopharyngeal

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D FIG 22-1 Normal nasopharynx on CT and MRI. A, Axial postcontrast CT image shows eustachian tube oriice (arrow in front), torus tubarius (*), and lateral pharyngeal recess (arrow behind) along the lateral wall of nasopharynx. Deep to posterior wall of nasopharynx are longus capitus (LC) muscles. B, Reformatted coronal CT image in same patient shows lateral pharyngeal recess (arrow) and torus tubarius (*). C, Axial postcontrast T1-weighted MRI shows eustachian tube oriice (arrow in front), torus tubarius (*), and lateral pharyngeal recess (arrow behind) along lateral wall of nasopharynx. Deep to posterior wall of enhancing nasopharyngeal mucosa are longus capitus (LG) muscles. D, On axial postcontrast T1-weighted MRI slightly inferior to C, the tensor levator palatini (*) and levator veli palatini (+) muscles are seen.

mucosal space cyst lodged between the prevertebral muscles. It varies in diameter from a few millimeters to several centimeters. On CT scans, a small cyst may be missed, but a larger one usually is seen as a hypodense luid-attenuation lesion (Fig. 22-2A). CT attenuation of the cyst increases, as does its protein content, and occasionally it may mimic a soft tissue mass. On MRI the T1-weighted signal intensity increases from low to high with increasing protein content. The cyst is

bright on T2-weighted (see Fig. 22-2B) and luid-attenuated inversion recovery (FLAIR) images, with thin peripheral enhancement on postcontrast images.

Persistent Canalis Basilaris Medianus. Persistent canalis basilaris medianus (CBM) is a rare and typically asymptomatic congenital anatomic variant of the basiocciput, believed to arise from

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FIG 22-2 Thornwaldt cyst. A, Low-attenuation well-circumscribed mass (arrows) in midline of nasopharynx on postcontrast axial CT image. B, The mass (arrows) is of luid signal on axial T2-weighted image.

FIG 22-3 Persistent canalis basilaris medianus is seen as a well-corticated lucency in the basiocciput (arrow).

notochordal remnants. It occurs in approximately 2% to 3% of adults as a well-deined corticated tubular structure, usually over 2 mm in diameter, originating on the intracranial surface of the basiocciput in close proximity to the anterior rim of the foramen magnum (Fig. 22-3). It is thought to represent an embryologic remnant demarcating the cephalic end of the notochord and corresponds to the course of the notochordal canal in the caudal basiocciput. A complete CBM traverses entirely through the basioccipital bone, whereas an incomplete CBM can extend partially through either the cranial or pharyngeal portions of the basiocciput but does not extend all the way through to the other surface. Clival defects from this vestige can be associated with several anomalies. MRI may detect accompanying

FIG 22-4 Fossa navicularis is seen as a notch-like defect in the basiocciput (arrow).

cysts and help differentiate between other possible etiologies, such as a cephalocele, and ecchordosis physaliphora, which is usually intradural within the prepontine cistern and is attached to the dorsal wall of the clivus via pedicles.51

Fossa Navicularis. Fossa navicularis is a notchlike bone defect in the basiocciput (Fig. 22-4) and is also an incidental imaging inding. Its incidence is around 3%, with many being less than 2 mm in size. Rarely, lymphoid tissue can be found within a prominent fossa

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navicularis, what some authors have termed fossa navicularis magna. Transmission of infection from oropharyngeal soft tissues via the fossa navicularis has been rarely reported as a cause of clival osteomyelitis, raising the possibility of affected patients being more susceptible to other infections such as meningitis. It is important to be aware of this rare congenital variant to prevent mischaracterization with the many more worrisome possibilities and possibly avoid biopsy or unnecessary treatment attempts.72

Craniopharyngeal Canal. The craniopharyngeal canal (CPC) is a rare well-corticated defect through the midline of the sphenoid bone, extending from the loor of the sella turcica to the roof of the nasopharynx (Fig. 22-5). The CPC is postulated to arise from an error in the normal development of the pituitary gland. It is a rare but important entity to recognize in the evaluation of nasopharyngeal or midline skull base lesions, because correct diagnosis may indicate pituitary dysfunction and obviate the need for surgery, thus preventing iatrogenic hypopituitarism or cerebrospinal luid (CSF) leak. CPCs have previously been described as either small (70%) despite early small primary lesions, the other symptoms being otitis media (due to eustachian tube obstruction), sore throat, epistaxis, headache, and cranial nerve neuropathies in advanced cases.15,23 Staging and treatment principles. The criteria given in the seventh edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for tumor-node-metastasis (TNM) staging of NPC are provided in Box 22-1. Surgery is unable to achieve clear resection margins, and radiotherapy (RT) remains the mainstay of treatment. Early-stage disease (T1 tumors without nodal metastases) treated with RT have a 5-year survival of 75% to 90%.28 In more advanced NPC, concurrent chemoradiation is the standard of care.47 Recently, transoral robotic surgery (TORS) has been used for local recurrence of NPC. Spread patterns. NPC usually originates in the lateral pharyngeal recess (Fig. 22-13A) and spreads mucosally, submucosally, and beyond the conines of the nasopharynx as well. Spread to the torus tubarius results in obstruction of the eustachian tube with resultant serous otitis media. Spread to the nasal cavity anteriorly or inferiorly into oropharynx is classiied as T1 disease. More commonly, early disease spread is seen posterolaterally into the parapharyngeal space (T2 disease) through the sinus of Morgagni. Further posterolateral spread into the carotid space may occur, with invasion of CNs IX, X, XI, and XII, with resultant palsies (T4 disease).16 On axial images, hypoglossal nerve palsy results in fatty replacement of the affected side of the tongue along with prolapse of the hemitongue into the oropharynx, indicating hypotonia.13 Posterior spread to the retropharyngeal space, prevertebral muscles, and vertebrae may occur and is associated with increased incidence of cervical nodal metastases.17 Superior extension into the sphenoid sinus and skull base upstages to T3 disease (see Fig. 22-13B). Cranial spread can also occur directly

through the foramen ovale (see Fig. 22-13C) or foramen lacerum (located immediately superior to the lateral pharyngeal recess) into the middle cranial fossa or through the jugular foramen into the posterior cranial fossa, upstaging the tumor to T4 disease.17 Perineural spread along the mandibular nerve through the foramen ovale (see Fig. 22-13D) can cause denervation atrophy of the muscles of mastication.64 Intracranial spread may extend to involve the dura mater, cavernous sinus, Meckel’s cave (see Fig. 22-13D) and prepontine cistern. Lateral extension to the masticator space or infratemporal fossa is also T4 disease (see Fig. 22-13D) and can cause trismus.17 Anteriorly, lateral spread through the sphenopalatine foramen extends into the pterygopalatine fossa, from where tumor can spread (a) along the maxillary nerve (Fig. 22-14A) through the foramen rotundum to the intracranial cavity, (b) through the inferior orbital issure into the orbital apex (T4 disease), (c) through the vidian canal into the carotid canal, (d) through the superior orbital issure into the cranial cavity, and (e) through the pterygomaxillary issure into the infratemporal fossa.12 The primary echelon nodes in NPCs are level IIb and lateral retropharyngeal group (see Fig. 22-14B), the other nodal levels being III, IV, and V.17 Spread to supraclavicular nodes is regarded as N3b (see Box 22-1). Pretreatment imaging features. On CT and MRI, NPC shows nonspeciic imaging features and cannot be differentiated with certainty from lymphoma or minor salivary gland tumors. Hence the primary role of pretreatment imaging is complete disease staging to help plan optimal treatment. CT and MRI are complementary in evaluating the locoregional extent of NPC, but MRI is the technique of choice because it is more sensitive for depicting skull base invasion, perineural spread, invasion of dura and cavernous sinuses, and retropharyngeal adenopathy.36 Cortical erosion is best studied on CT.59 Asymmetry of the nasopharynx is an early feature, but this may also be seen in asymmetric lymphoid hyperplasia; obliteration of the fat stripe between the tensor and levator veli palatini is a more reliable early imaging feature of NPC. The above features should prompt attention to serous mastoiditis, which suggests eustachian tube dysfunction, and lymphadenopathy in the ipsilateral neck, particularly in the retropharyngeal group.88 In more advanced cases, imaging reveals invasion of adjacent spaces. Noncontrast and non–fat-suppressed T1-weighted sequences are most useful to demonstrate obliteration of the fat intensity between the adjacent space and tumor (which is isointense). NPC displays intermediate signal on T2-weighted sequences, with intense enhancement on postgadolinium images. Fat-suppressed contrastenhanced images, particularly in the coronal plane, are valuable for conirming skull base marrow invasion (see Fig. 22-13B), and for demonstrating orbital extension, perineural spread (see Figs. 22-13D and 14A), and dural invasion. Thickening and enhancement of dura mater alone, however, could either represent intracranial extension of tumor or reactive inlammation (see Fig. 22-13C).16 Foraminal invasion due to perineural spread is seen as widening and increased enhancement (see Fig. 22-13D). Denervation atrophy due to perineural spread is seen as hyperintense signal in the masticator muscles on T2-weighted images, with increased enhancement in the acute-subacute stage, and as diffuse muscle hyperintensity on both T1- and T2-weighted images, with reduced bulk in the chronic phase. Direct tumor invasion increases the muscle bulk, is focal rather than diffuse, and has signal intensity similar to tumor.64 NPC and nodal metastases are usually FDG avid. Currently FDG-PET/CT is considered useful for mapping precise nodal burden, for evaluating distant metastases, and in the workup of unknown

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Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ Nasopharynx T1 Tumor conined to the nasopharynx, or tumor extends to oropharynx and/or nasal cavity without parapharyngeal extension* T2 Tumor with parapharyngeal extension* T3 Tumor involves bony structures of skull base and/or paranasal sinuses T4 Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit or with extension to infratemporal fossa/masticator space Oropharynx T1 Tumor 2 cm or less in greatest dimension T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension T3 Tumor more than 4 cm in greatest dimension or extension to lingual surface of epiglottis T4a Moderately advanced local disease Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible^ T4b Very advanced local disease Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery Regional Lymph Nodes (N) Nasopharynx The distribution and the prognostic impact of regional lymph node spread from nasopharyngeal cancer, particularly of the undifferentiated type, are different from those of other head and neck cancers and justify the use of a different N classiication scheme.

NX—Regional lymph nodes cannot be assessed N0—No regional lymph node metastasis N1—Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, 6 cm or less, in greatest dimension.+ N2—Bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa+ N3—Metastasis in a lymph node(s)+ > 6 cm and/or to supraclavicular fossa+ N3a—Greater than 6 cm in dimension N3b—Extension to the supraclavicular fossa++ Oropharynx^^ NX—Regional lymph nodes cannot be assessed N0—No regional lymph node metastasis N1—Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N2—Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension N2a—Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension N2b—Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension N2c—Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension N3—Metastasis in a lymph node more than 6 cm in greatest dimension

From Edge S, Byrd DR, Compton CC, et al (eds.): AJCC Cancer Staging Manual, ed 7, New York, 2010, Springer-Verlag. *Note: Parapharyngeal extension denotes posterolateral extension of tumor. ^ Note: Mucosal extension to lingual surface of epiglottis from primary tumors of base tongue or vallecula does not constitute invasion of larynx. + Midline nodes are considered ipsilateral nodes. ++ Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is deined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder. Note that this would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b. ^^ Note: Metastases at level VII are considered regional lymph node metastases.

primary cancers presenting with cervical adenopathy.61,90 National Comprehensive Cancer Network (NCCN) practice guidelines recommend PET-CT to evaluate for distant metastases when stage III or IV disease is present. Imaging is also valuable for treatment planning. Accurate delineation of target volume with MRI as well as PET/CT results in more precise delivery of RT and indirectly improves local control and disease-speciic survival.36 Imaging can also provide prognostic indicators. The most important prognostic criterion predictive of outcome and survival in NPC was CT-derived primary tumor volume greater than 50 mL during RT planning.8 Response assessment and surveillance. The NCCN guidelines recommend a baseline scan to be obtained within 6 months of completion of chemoradiation in patients with T3-4 and/or N2-3 disease. Further imaging is only recommended “as indicated based on signs/ symptoms.”65 Response assessment can be performed either with MRI or PET/ CT, with equivalent reported accuracy for detection and restaging.19 CT has inferior soft tissue resolution to differentiate between posttreatment changes and residual or recurrent disease. A baseline posttreatment MRI scan is usually performed at 2 to 3 months after therapy because it is perceived to be valuable for detecting subclinical residual

adenopathy and also serves as a baseline to detect future, more subtle recurrences. If the pretreatment study showed iniltration of the parapharyngeal space, pterygopalatine fossa, orbits, or the skull base, abnormal signal intensity may persist. The initial scan may also show signiicant posttreatment edema of the pharyngeal mucosa. There should be no residual enlarged lymph nodes, however; if these are found on the new baseline scan, a neck dissection is typically performed. The timing of PET/CT is critical, with a systematic review and meta-analysis reporting a high negative predictive value of 95% in scans done after 12 or more weeks.32 Earlier response assessment to chemoradiotherapy at 20 days and 50 days has been evaluated with diffusion-weighted MRI with promising results.9 High pretreatment ADC values and signiicant increase in ADC following initiation of induction chemotherapy showed better response to deinitive treatment with concurrent chemoradiation. Use of plasma Epstein-Barr virus (EBV) DNA for initial assessment, followed by PET/CT or MRI in positive cases, has been recommended. Wang et al. found plasma EBV DNA to have 100% accuracy in detecting recurrence of NPC.83 A recent study also found that patients with a negative 3-month PET/CT had limited beneit from subsequent PET surveillance.38

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D FIG 22-13 Nasopharyngeal carcinoma. A, Axial T1-weighted postcontrast MRI shows a small enhancing lesion centered in the left lateral pharyngeal recess (arrow). B, Coronal T1-weighted postcontrast MRI shows an enhancing mass invading skull base marrow (arrow). C, Coronal T1-weighted postcontrast MRI shows an enhancing mass invading the foramen ovale (arrow), with intracranial extension (T4 tumor) causing dural thickening. D, Coronal T1-weighted postcontrast MRI shows perineural spread through a widened foramen ovale into Meckel’s cave (long arrow). Short arrow on the contralateral side shows the normal Meckel’s cave. Dashed arrow shows extension to masticator space (T4 tumor).

On MRI, nonenhancing tissue with dark signal on T2-weignted sequences represents mature ibrosis. However, immature ibrosis (being cellular) may show intermediate to high T2-weighted signal intensity and may enhance, mimicking residual/recurrent disease.60 Following RT the nasopharynx may appear asymmetric and tends to lose its normal contours and develops a ibrosed appearance with effacement of the lateral pharyngeal recess primary site (Fig. 22-15AB). Recurrent/residual tumor has bulging contours with enhancement (see Fig. 22-15C) that can be detected with certainty on PET/CT as an FDG-avid lesion (see Fig. 22-15D). Regression on serial scans may indicate post-RT changes, but unchanged lesions remain suspicious for occult or recurrent disease. Progressing masses or the appearance of a new node suggest recurrence.11 Another uncommon manifestation of

recurrence is meningeal iniltration in the posterior fossa through the jugular foramen or foramen magnum without any visible nasopharyngeal component, which should prompt meticulous scrutiny of these regions.14

Nasopharyngeal Lymphoma. The head and neck is the second most common site of non-Hodgkin’s lymphoma (NHL). NHL is most frequently found in Waldeyer’s ring. Within Waldeyer’s ring the nasopharynx is the second most common site of disease after the tonsil. It is a homogeneous tumor that tends to diffusely involve all walls of the nasopharynx and spread in an exophytic fashion to ill the airway, rather than iniltrating into the deep tissues (Fig. 22-16). Primary NHL more commonly spreads supericially to involve the nasal cavity or

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FIG 22-14 Nasopharyngeal carcinoma. A, Axial T1-weighted postcontrast MRI shows enhancement along pterygopalatine fossa, suggestive of perineural spread along V2 (maxillary nerve). B, Axial T2-weighted MRI shows a rounded retropharyngeal node (arrow) located medial to the carotid vessels.

oropharynx; lymphadenopathy is frequent and extensive, and the nodes may show necrosis and matting. A large tumor that ills the nasopharynx, with no or minimal invasion into deep structures and a propensity to extend down into the tonsil rather than up into the skull base, may suggest the diagnosis of NHL over nasopharyngeal carcinoma.44

Nasopharyngeal Rhabdomyosarcoma. Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, with the head and neck region accounting for 35% to 40% of cases. It is a highly malignant tumor thought to arise from striated muscle progenitor cells, with four major histologic subtypes. Embryonal RMS is the most common subtype in the head and neck region, has an intermediate prognosis, and rarely involves regional lymph nodes. Alveolar RMS and undifferentiated sarcoma are both associated with a relatively poorer prognosis. Nasopharyngeal RMS presents with indolent minimal and nonspeciic symptoms of nasal, aural, or sinus obstruction, with or without a mucopurulent or sanguineous discharge. Imaging is critical in deining the exact size and location of the lesion and offering a differential diagnosis. It makes an essential contribution to staging and detecting extension into the intracranial compartment, involvement of cranial nerves, osseous erosion of the skull base, orbital involvement, encasement of the carotid or vertebral arteries, perineural spread, lymphadenopathy, and distant metastases (Fig. 22-17). Imaging also helps guide a biopsy procedure by showing the best route to obtain representative material. Treatment is usually multimodal, with chemotherapy, surgery, and radiation therapy.26,34

Miscellaneous Inlammatory Pseudotumor of the Nasopharynx. Inlammatory pseudotumor of the nasopharynx is a rare benign idiopathic disease often mistaken for a neoplasm or infection, owing to its aggressive behavior and clinical presentation. It can present as a progressively

destructive skull base mass and should be considered when repeated tissue biopsies reveal acute or chronic inlammation without evidence of malignant disease or infection. Recognition of inlammatory pseudotumor is critical because it usually mimics squamous cell carcinoma or an aggressive angioinvasive fungal infection on imaging. Much like other inlammatory or neoplastic processes of the nasopharynx, it can present with unilateral hearing loss or otitis media owing to eustachian tube obstruction, multiple cranial nerve palsies resulting from skull base or cavernous sinus invasion, and stroke resulting from compromise of intracranial vasculature (primarily internal carotid arteries at or below the skull base). On imaging it is seen as an ill-deined iniltrative soft tissue lesion with inlammatory fat stranding on CT or MRI. Inlammatory pseudotumor is a diagnosis of exclusion, with differential considerations including inlammatory myoibroblastic tumor, immunoglobulin (Ig)G4-related sclerosing lesion, Rosai-Dorfman disease, EBV-related inlammatory pseudotumor, calcifying ibrous pseudotumor, lymphoma, and NPC. Because of their aggressive presentation, tissue sampling is essential for making the diagnosis, which usually shows only inlammatory changes. An important diagnostic clue is the absence of cervical lymphadenopathy despite the presence of an aggressive destructive mass. Despite their aggressive appearance, these lesions respond well to steroid treatment.18

OROPHARYNX Anatomy The oropharynx is the part of the pharynx that lies behind the oral cavity (can be seen through the open mouth). It is separated from the oral cavity by the circumvallate papillae of the tongue, the anterior tonsillar pillars, and the soft palate. The base of tongue is the posterior third of the tongue, bounded anteriorly by the circumvallate papillae, laterally by the glossotonsillar sulci, and posteriorly by the epiglottis. The vallecula is a strip of mucosa that is the transition from the base

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D FIG 22-15 Posttreatment MRI in nasopharyngeal carcinoma. Axial (A) and coronal (B) T1-weighted contrastenhanced MRI in two different patients shows mild asymmetry and enhancement in the lateral pharyngeal recess (arrows). These are posttreatment changes, and follow-up showed complete response. C, Contrastenhanced axial CT shows residual heterogeneously enhancing lesion along the left lateral nasopharyngeal wall (arrow) and parapharyngeal space, suspicious for recurrence. D, PET/CT shows FDG-avid mass (arrow) suggestive of residual disease.

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D FIG 22-16 Nasopharyngeal lymphoma in a 63-year-old male with 5-month history of nasal congestion progressing to nasal obstruction. A, Axial postcontrast CT image shows mass illing the nasopharynx, with extension into the parapharyngeal spaces (long black arrows), carotid spaces (long white arrows), and retropharyngeal and prevertebral spaces (short black arrows). B, Axial CT image more inferiorly shows extension of the mass into the oropharynx (arrows) and numerous enlarged lymph nodes (*). C, The mass (*) is associated with diffuse iniltration into clivus, basisphenoid, and sphenoid sinus (arrows), as seen on sagittal precontrast T1-weighted image. D, The mass is only mildly hyperintense on axial T2-weighted image (long arrows) with deep extension into carotid spaces visualized (short arrows).

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E FIG 22-17 Nasopharyngeal rhabdomyosarcoma in an 8-year-old with 1-week history of headache, left eye pain, ptosis, and anisocoria. A, On axial postcontrast CT there is a hypodense rim-enhancing mass (arrows) centered in the left nasopharynx, with extension into parapharyngeal space. B, The mass (arrows) is isointense to muscle on axial T1-weighted precontrast image. Iniltration into the left carotid space is present (arrowhead). C, The mass is hyperintense on axial T2-weighted image (arrows), with carotid space extension (arrowhead) of similar signal. D, There is enhancement following contrast on fat-saturated axial T1-weighted image. E, Coronal postcontrast T1-weighted image shows extension of the mass (long black arrows) through the skull base in region of the foramen ovale into the cavernous sinus (short black arrows). There is dural enhancement along the loor of the left middle cranial fossa (arrowhead). Normal foramen ovale is seen on the right (white arrow).

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FIG 22-18 Normal oropharynx on CT and MRI. A, Axial postcontrast CT image shows the vallecula (V) between the base of tongue (*) and epiglottis. B, The same structures are seen on axial postcontrast T1-weighted image. C, Sagittal T1-weighted MRI without contrast shows the palate (P), hyoid (H), tongue base (*), and vallecula (V), the latter being just anterior to the epiglottis.

of the tongue to the epiglottis and is considered part of the oropharynx (Fig. 22-18). Thus the oropharynx includes the base of the tongue (posterior third of the tongue and the lingual tonsil), the vallecula, the soft palate and uvula, the lateral pharyngeal walls including the palatine tonsils and tonsillar pillars, and the posterior pharyngeal wall, extending from the plane of the soft palate/hard palate junction to the level of the pharyngoepiglottic folds at the hyoid bone. Posteriorly the superior and middle constrictor muscles separate the oropharynx from the prevertebral muscles overlying the second and third cervical vertebrae. Superiorly the oropharynx communicates with the nasopharynx, separated by the soft palate. Inferiorly the oropharynx is separated from the hypopharynx by the pharyngoepiglottic fold and from the larynx by the epiglottis and glossoepiglottic fold.33,56,62

The features of the lateral oropharyngeal walls include two tonsillar pillars (faucial arches): • The anterior tonsillar pillar (palatoglossus muscle) • The posterior tonsillar pillar (palatopharyngeus muscle) Between them lies the tonsillar fossa, which contains the palatine tonsil on each side.

Congenital Lesions Lingual Thyroid. Ectopic thyroid tissue at the base of the tongue/ loor of the mouth is referred to as lingual thyroid. Embryologic descent of thyroid anlage occurs between the third and seventh week of gestation from the foramen caecum, situated at the base of the tongue, to its usual position in the neck. Complete failure of descent results in a lingual thyroid. This may occur in association with thyroglossal duct cyst and is seen more commonly in females.58 This abnormality is

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FIG 22-19 Lingual thyroid found incidentally. A, Axial postcontrast CT image shows round hyperdense mass (arrow) in midline of tongue base in expected location of foramen cecum. B, The lingual thyroid (arrow) is well seen on sagittal reformatted CT image.

usually incidentally detected, but some patients may develop dysphagia, dyspnea, or obstructive sleep apnea. On imaging, these lesions appear as well-circumscribed round or oval lesions at the loor of the mouth/base of the tongue in the midline, with features similar to thyroid tissue. Characteristically the lesions are hyperdense in attenuation on noncontrast CT and demonstrate avid enhancement (Fig. 22-19). On MRI, the lesion is usually isointense to skeletal muscle on T1-weighted and hyperintense on T2-weighted images. The lesion demonstrates high uptake on Tc-99m pertechnetate or radioiodine nuclear scan.70 Surgery may be performed if the patient has obstructive symptoms.

Thyroglossal Duct Cyst. A thyroglossal duct cyst (TGDC) is the most common congenital neck mass, accounting for 70% of all congenital neck anomalies.31,45,46 Embryologically the thyroglossal duct (which means pertaining to the thyroid gland and the tongue) extends from the foramen cecum in the base of tongue to the thyroid bed through the hyoid bone. Any portion of this duct that fails to involute results in a TGDC. It is located in the midline (75%) or slightly paramidline (25%), embedded in the infrahyoid strap muscles. The most common location of a TGDC is infrahyoid (65%), whereas only 15% are at the level of the hyoid bone, and 20% are suprahyoid in the location in the anterior neck. The more inferior the cyst, the more likely it is to be off the midline. About 50% of patients present before 20 years of age, though there is a small percentage (15%) who present at older than 50 years, with no reported gender predilection. The most common clinical presentation is that of a painless palpable cystic neck mass near the hyoid bone in the midline. Approximately one third present with a concurrent or prior infection. As a result of their intimate relationship with the foramen cecum and hyoid bone, the TGDC usually moves with swallowing or protrusion of the tongue on physical exam.2,46,84 The uncomplicated TGDC can be anechoic, homogeneously hypoechoic, or heterogeneous in echogenicity on ultrasound, without internal vascularity on

color Doppler ultrasound. The uncomplicated TGDC is well deined with low CT attenuation, has luid signal intensity on MRI, and lacks a solid enhancing component. The thin cyst wall may demonstrate peripheral contrast enhancement (Fig. 22-20). A complicated TGDC with superimposed infection may have peripheral contrast enhancement, internal septations, and may be associated with edema and stranding of the surrounding soft tissues. Ectopic thyroid tissue may be present in the TGDC and can be a site of thyroid carcinoma, 80% of which are of papillary cell origin. The surgical resection of a symptomatic TGDC is Sistrunk’s procedure, which involves resection of the thyroglossal remnant together with a central portion of hyoid bone and cuff of tissue around the thyroglossal tract from the hyoid bone to the foramen cecum.2

Congenital Cysts. Congenital cysts of the oropharynx have been described in the medical literature by various names such as tongue base cysts, epiglottic cysts, vallecular cysts, or lingual cysts.85 Histologically the cyst contains mucous glands with an external lining of squamous epithelium.39 These cysts are usually detected incidentally on imaging studies. Infrequently these can be seen in children who present with airway obstruction. Diagnosis is made on lexible laryngoscopy or bronchoscopy. CT and MRI are useful to narrow the differential diagnosis. Typical imaging indings are a sharply demarcated cystic lesion that does not enhance. Surgical treatment involves marsupialization under anesthesia.

Lymphatic/Venolymphatic Malformation. A lymphatic malformation is a developmental lesion composed of dilated lymphatic channels. These are caused by rests of lymph sacs left during embryogenesis. A venolymphatic malformation has combined elements of venous and lymphatic malformations. Most lesions are found in the head and neck region. Approximately 50% of these lesions are found at birth and 80% to 90% are detected within the irst 2 decades.89 These are benign lesions and do not have malignant potential. Depending on the size of

CHAPTER 22

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FIG 22-20 Thyroglossal duct cyst in 27-year-old with neck pain. A, Axial postcontrast CT image shows lowattenuation mass with thin enhancing rim (arrows) in midline of infrahyoid neck, embedded within strap muscles. B, The cyst (arrows) is seen just below hyoid on sagittal reformatted CT image.

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FIG 22-21 Lymphatic malformation in 4-year-old with neck mass since birth. A, Axial postcontrast CT image shows multispatial heterogeneous, predominantly cystic neck mass (long arrows) with extension to oropharynx (short arrows). B, Coronal reformatted CT image shows extension to oropharynx (arrows).

the cysts, these lesions can be classiied as microcystic or macrocystic. These can be located in a single neck space or can be transspatial (Fig. 22-21A). On imaging these lesions appear as uniloculated or multiloculated cystic neck masses with imperceptible walls. Fluid-luid levels may be seen. Typically these lesions do not demonstrate enhancement or may have minimal peripheral enhancement (see Fig. 22-21B). Enhancement within a lesion that otherwise resembles a lymphatic malformation suggests it is a mixed lesion with a component of venous malformation. These lesions can rapidly enlarge in size if there is an infection or intralesional hemorrhage and cause symptoms, predominantly due to locoregional mass effect on surrounding structures.

Macrocystic lymphatic malformations have a low tendency to recur, whereas microcystic malformations have a high recurrence rate. Treatment options include percutaneous sclerotherapy or surgery. Percutaneous sclerotherapy has shown good results both as primary treatment and also treatment of lesions that recur after surgery.75

Macroglossia. Macroglossia refers to enlargement of the tongue. It is usually seen in children and is associated with conditions like Down syndrome, Beckwith-Wiedemann syndrome, congenital hypothyroidism, and mucopolysaccharidoses. The tongue can also appear large in children with micrognathia, such as in cases of Pierre Robin

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syndrome.25 Rarely macroglossia can be seen in adults in cases of lymphoma and amyloidosis. In some cases, macroglossia may result in dysphagia or airway compromise and require surgical correction.53

Oropharyngeal Airway Compromise (Obstructive Sleep Apnea and Pickwickian Syndrome). Obstructive sleep apnea (OSA) is the most common type of sleep apnea. It is caused by upper airway obstruction during sleep. Common signs and symptoms include loud snoring, excessive daytime sleepiness and fatigue, morning headaches, and insomnia. OSA has been implicated to cause sleep fragmentation and hypoxemia, which in turn contribute to various adverse effects,4 which include increased risk of motor vehicle accidents and adverse cardiovascular risk. These patients are also at an increased risk for stroke and hypertension.86 Most cases of OSA result from narrowing of the posterior nasopharynx or retroglossal airways. Enlarged lingual or palatine tonsils and adenoids contribute to airway narrowing. Glossoptosis, deined as posterior motion of the tongue during sleep, is also implicated because it causes narrowing of the airway. Glossoptosis can occur in cases of macroglossia or decreased muscular tone. Hypopharyngeal collapse can also occur during sleep in patients with decreased muscular tone. Cine-MR studies have been used to document the dynamic change in tongue position and the coniguration of the hypopharynx during sleep. Pickwickian syndrome (also known as obesity hypoventilation syndrome) is named after a character Charles Dickens originally described in his novel The Pickwick Papers. It refers to a condition of hypoventilation, hypoxemia, somnolence, and hypercapnia in obese people.

Inlammatory Lesions

FIG 22-22 Peritonsillar abscess in 25-year-old with 3 days of left throat pain and odynophagia. There is enlargement of left palatine tonsil containing a low-attenuation rim-enhancing collection.

Tonsillitis and Peritonsillar Abscess. Tonsillitis and peritonsillar abscess are the most commonly encountered acute neck infections among adolescents and young adults, with peritonsillar abscess accounting for one third of all soft tissue abscesses of the head and neck.7,71 Symptoms include severe unilateral sore throat, fever, tender cervical lymphadenopathy, dysphagia, pharyngotonsillar exudates, otalgia. and trismus. The most common pathogens are β-hemolytic Streptococcus, Staphylococcus aureus, Pneumococcus, and Haemophilus inluenzae. Acute tonsillitis may suppurate and internally cavitate to create an intratonsillar abscess; however, a true tonsillar abscess is rare. Infection that penetrates the ibrous tonsillar capsule and the peritonsillar space—a potential space between the tonsillar capsule and the superior constrictor muscle—is more common. The infection may then extend into the adjacent parapharyngeal, masticator, or submandibular spaces. The resulting peritonsillar cellulitis resolves over several days when antibiotics are administered; if it goes untreated, a peritonsillar abscess develops, typically along the superior tonsillar pole. Imaging is not routinely performed if the diagnosis is clinically apparent.35 However, contrast-enhanced CT is used if the diagnosis is uncertain, a full clinical examination is dificult because of severe trismus, a deep neck space infection or complication is suspected, or the patient does not respond to therapy. CT indings of peritonsillar cellulitis include tonsillar enlargement and linear striated enhancement of the palatine tonsils and posterior pharyngeal soft tissues. Medial apposition of the enlarged tonsils results in a “kissing tonsils” appearance. Central liquefaction with surrounding rimlike enhancement is diagnostic of peritonsillar abscess (Fig. 22-22). Peritonsillar cellulitis is treated with antibiotics, whereas abscess requires needle aspiration or surgical drainage.54,71 When a peritonsillar abscess is clinically suspected, the radiologist’s responsibilities are the following: • To conirm the diagnosis • To determine the degree of airway compromise

• •

To determine whether the abscess has spread into the deep neck spaces To assess the status of the internal carotid artery and internal jugular vein in the case of a deeply extending abscess

Postinlammatory Sequelae. Occasionally a second branchial cleft cyst drains into the tonsillar fossa, and this should be considered when a istula there is identiied. Alternatively, actinomycosis or dermal sinus tracts could cause peritonsillar or tonsillar istulae. After tonsillitis, dystrophic calciication or clumps of tonsillar calciication called tonsilloliths may be detected incidentally on CT scans; these are indicative of previous or chronic tonsillitis. Less commonly they may be seen in the adenoids or the lingual tonsil.

Benign Neoplasms Benign tumors are rare and include benign mixed tumor, schwannoma, hemangioma, myoibroma, and amyloidoma. These have nonspeciic imaging features, and biopsy is required for diagnosis.

Malignant Neoplasms The commonest neoplasm of the oropharynx (90%) is squamous cell carcinoma (SCC).74 Lymphomas, minor salivary gland tumors, and sarcomas comprise the remainder of malignant neoplasms. Imaging cannot reliably differentiate these neoplasms from SCC.

Oropharyngeal Squamous Cell Carcinoma Etiopathogenesis and symptoms. Oropharyngeal SCC (OPSCC) has two etiologic subtypes—one related to alcohol and tobacco use and another less aggressive variety related to human papillomavirus (HPV) infection, which has a better prognosis.20 The presenting symptoms are nonspeciic, such as sore throat, dysphagia, and otalgia in the vast majority of patients, with pain and trismus in more invasive tumors.74

CHAPTER 22 Staging and principles of treatment. The seventh edition AJCC Cancer Staging Manual criteria for TNM staging of OPSCC are provided in (see Box 22-1. OPSCC is treated with RT/surgery or a combination of both. Although TORS may have a role for early-stage oropharyngeal cancers, stage III and IV disease are usually treated with concurrent chemoradiation.24 In view of better prognosis of HPVpositive cancers, less intensive treatment regimens (deescalation treatment protocols) are currently being investigated.52

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Spread patterns. OPSCC can arise from the tonsil, tongue base, soft palate, or posterior pharyngeal wall. Tonsillar SCC mostly arises from the anterior tonsillar pillar (ATP) and tonsil, lesions from the posterior tonsillar pillar being rare. Anterior spread is along the palatoglossus muscle to the base of the tongue inferiorly (Fig. 22-23A-C) and soft palate superiorly. Lateral spread is common, causing obliteration of the parapharyngeal fat. Superior and inferior spread occurs along the nasopharyngeal and hypopharyngeal wall. Spread along the

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D FIG 22-23 Oropharyngeal carcinoma. A, Axial T2-weighted MRI shows bilateral prominent palatine tonsils that appear hyperintense (arrows). B, Axial T2-weighted MRI shows a bulky mass involving left lateral pharyngeal wall and palatine tonsil (solid arrow). Dashed arrow shows contralateral normal palatine tonsil. C, Axial contrast-enhanced MRI shows an enhancing mass involving left tonsil extending into tongue base (arrows). Long arrow on the right shows contralateral normal lingual tonsil. Dashed arrow shows a necrotic node. D, Sagittal T2-weighted MRI shows a squamous cancer of the soft palate as a lobulated mass (arrows).

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pterygomandibular raphe to the retromolar trigone is often seen. Advanced cases invade the mandible, masticator space, or infratemporal fossa to reach the skull base.49 Lymphatic spread is seen in 76% of patients at presentation, with level II being the irst-echelon nodes; level IB, II-V, and retropharyngeal nodes may also be involved.27 Soft palate SCC usually arises from the oral surface of the palate (see Fig. 22-23D). It spreads anteriorly to the hard palate and inferiorly along the ATP to the tongue base. Lateral extension to the parapharyngeal space may extend to the skull base. Superior spread to the

nasopharynx and occasionally perineural spread along the palatine nerves may reach the pterygopalatine fossa.27,84 Lymphatic spread occurs to level I, II, and retropharyngeal nodes, and bilateral nodal metastases are known.49,84 Tongue base SCC may spread anteriorly into the oral tongue and further below to the sublingual space to invade the lingual neurovascular bundle as well as the hyoglossus, genioglossus, and mylohyoid muscles (Fig. 22-24A-B). Perineural spread may occur along the lingual nerve to reach the mandibular nerve. Perineural spread,

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D FIG 22-24 Oropharyngeal carcinoma. A, Axial T2-weighted MRI shows normal extrinsic muscles, paired genioglossi (*), and hyoglossi (arrows). B, Axial T2-weighted MRI shows large intermediate signal–intensity tumor (outlined by arrows) invading both-sided extrinsic muscles (compare with A). C, Axial postcontrast T1-weighted image shows normal enhancement in bilateral lingual tonsils (arrows); hence careful attention to asymmetry in enhancement is needed to detect tumor. D, Coronal postcontrast T1-weighted image shows brightly enhancing tumor crossing midline (arrow).

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FIG 22-25 Posterior pharyngeal wall squamous carcinoma. A, Sagittal reformatted postcontrast CT image shows a posterior pharyngeal wall mass (arrows). B, Axial postcontrast CT image shows a posterior pharyngeal wall mass (arrow). Dashed arrow shows intact fat plane with prevertebral muscles. This plane is best evaluated on T1-weighted MRI sequences and when well seen on MRI rules out prevertebral fascial invasion with a high negative predictive value.

vascular invasion, and high T stage are adverse prognostic factors. Spread along the palatoglossus can reach the ATP and further into the soft palate. Posterior spread to the valleculae and preepiglottic space may reach the pyriform sinus. However, early tongue base OPSCC arising from the lingual tonsil may be dificult to differentiate from normal lymphoid tissue in this region (see Fig. 22-24C). Loss of symmetry due to spread to adjacent structures can help identify disease.49 Lymphatic metastases occur in 60% and are seen to level II-IV nodes and to submandibular nodes when the loor of the mouth is invaded. Disease may cross the midline (see Fig. 22-24D) and cause bilateral nodal metastases.27,84 Posterior pharyngeal SCCs are least common (Fig. 22-25) but may be involved by spread from adjacent lateral pharyngeal walls. Inferior spread to the hypopharynx may occur. It is important to rule out ixation of the prevertebral fascia (see Fig. 22-25B), which precludes surgical resection, although the majority of these lesions are treated with RT or concurrent chemoradiation.49 Isolated retropharyngeal adenopathy may be seen. Pretreatment imaging features. MRI is superior to CT for evaluating the locoregional extent of OPSCC (better soft tissue resolution), but CT best depicts cortical erosion.84 Normal tonsils are well seen on MRI, with hyperintense signal on T2-weighted sequences (see Fig. 22-23A). Although they can appear asymmetric, any obliteration of the parapharyngeal fat with an enlarged tonsil or associated adenopathy (see Fig. 22-23B-C) should be viewed with suspicion.27 Soft palate SCCs are best imaged with coronal and sagittal images (see Fig. 22-23D). In tongue base SCC, coronal and axial postcontrast T1-weighted sequences depict lingual vascular bundles. T2-weighted sequences best depict the extrinsic tongue muscles (see Fig. 22-24A-B), and the preepiglottic space is best seen on sagittal noncontrast T1-weighted sequences. Invasion of the preepiglottic space implies radical surgery, including a supraglottic laryngectomy, or alternatively

could be a relative surgical contraindication. Spread across the midline with invasion of both lingual vascular bundles also needs mention because this may require total glossectomy or could be an indication for nonsurgical therapy (chemoradiation). MRI is also useful to evaluate invasion of prevertebral fascia and musculature,40,50 to detect retropharyngeal adenopathy (using T2-weighted, short tau inversion recovery [STIR], and fat-suppressed contrast-enhanced sequences), and to depict skull base marrow involvement and intracranial dural invasion (using noncontrast T1 and fat-suppressed contrast-enhanced T1-weighted sequences). It can also detect perineural tumor spread along the greater and lesser palatine nerves into the pterygopalatine fossa (best seen with contrastenhanced fat-suppressed coronal T1-weighted sequences).30 Thickened and enhancing nerves and Meckel’s cave and bulging of the cavernous sinus may be direct signs of perineural spread. Indirect signs include foraminal enlargement, loss of normal fat around foramina or in the pterygopalatine fossa (seen with maxillary nerve invasion12), and denervation atrophy of the masticator muscles, visualized with mandibular nerve invasion. Imaging features suggestive of prevertebral fascial invasion (e.g., absent retropharyngeal fat plane) have an accuracy of only 60%. Imaging features suggestive of prevertebral muscle invasion, seen as altered T2 signal in the muscle, with irregular contour and enhancement also have a low positive predictive value but need to be recorded.50 However, preservation of the retropharyngeal fat plane on T1-weighted noncontrast sequences has high negative predictive value (97.5%) for absence of prevertebral fascial invasion.40 Marrow invasion is seen as replacement of the bright fat signal on coronal T1-weighted sequences with dark tumor signal intensity and with enhancement on postcontrast sequences. Imaging cannot reliably differentiate between HPV-positive and HPV-negative OPSCC. However, studies have reported that HPVpositive OPSCCs have cystic nodal metastases with well-deined

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FIG 22-26 PET-CT for detecting unknown primary. A, Axial postcontrast CT image shows mild thickness of the median glossoepiglottic fold (arrow). B, PET-CT detects the unknown primary as an FDG-avid lesion.

borders, whereas HPV-negative OPSCCs have metastatic nodes with ill-deined borders invading muscle.6 PET-CT is useful in high T stage cancers to evaluate for distant metastases and in cases presenting with cervical adenopathy to detect an unknown primary that may be seen in the palatine or lingual tonsils87,90 (Fig. 22-26). The main imaging-dependent prognostic indicators in OPSCC are high T and N stage, which are more signiicant than tumor volume.3 Studies evaluating MRI diffusion and perfusion and PET-CT to identify prognostic markers are ongoing. Response assessment and surveillance. MRI and PET-CT are both useful for response assessment. Diffusion-weighted imaging is also useful to detect residual disease. A recent study evaluating PET-CT at 3 months in HPV-positive OPSCC demonstrated high negative predictive value for locoregional failure in complete responders but poor sensitivity and positive predictive value.81 In patients with N2/N3 nodal disease treated with concurrent chemoradiation, absence of nodal disease on clinical examination with lack of nodal uptake on PET-CT is a safe indication to observe the neck without a planned neck dissection.21 The surveillance policy in OPSCC treated with RT or concurrent chemoradiation is not clearly deined. Imaging is known to detect local failure earlier than clinical examination. Asymmetry of the oropharynx with enhancement and bulging contours may suggest recurrent tumor and can be conirmed by PET-CT and/or biopsy. Baseline MRI and CT studies are useful for comparison with future studies, particularly in those with persisting asymmetry and negative biopsies. Routine subsequent PET surveillance in those with negative 3-month PET-CT is of limited beneit.38

HYPOPHARYNX Anatomy The hypopharynx lies behind the larynx in front of the C3-C6 vertebrae and extends from the tip of the epiglottis (or level of the hyoid bone) superiorly to the inferior border of the cricoid cartilage. It com-

municates anteriorly with the larynx, superiorly with the oropharynx, and inferiorly with the esophagus. It can be divided into three anatomic subsites: the pyriform sinus, the postcricoid area, and the posterior pharyngeal wall.

Pyriform Sinus. The pyriform sinus is a funnel-shaped or an inverted pyramid–shaped structure that begins superiorly at the glossoepiglottic fold and extends inferiorly, with its apex at the level of the cricopharyngeus muscle. It is bounded laterally by the thyroid lamina and posteriorly by the lateral wall of the hypopharynx. Its medial boundary is the lateral surface of the arytenoid cartilage and the aryepiglottic fold (Fig. 22-27A-B). Posteriorly it is open and continuous with the posterior pharyngeal wall. Its apex is where the anterior, lateral, and medial walls meet inferiorly.

Postcricoid Region. The postcricoid region forms the anterior wall of the hypopharynx and spans along the mucosa lining the posterior wall of the cricoid cartilage (see Fig. 22-27C-D). This area is the most dificult to examine by both mirror exam and direct laryngoscopy.

Posterior Pharyngeal Wall. The posterior pharyngeal wall extends from a plane drawn at the level of the tip of the epiglottis (some say the level of the vallecula or hyoid) to a plane at the inferior border of the cricoid. The superior and inferior margins of the hypopharynx blend with the posterior wall of the oropharynx and esophagus, respectively. It covers middle and inferior constrictor muscles and is separated from prevertebral fascia by the retropharyngeal space. The lining of the hypopharynx is stratiied squamous epithelium and has a rich submucosal network of lymphatics that exit superiorly through the thyrohyoid membrane into the superior and middle jugular nodes. Inferiorly the lymphatics drain to the paratracheal and low jugular nodes. The hypopharynx functions as a dynamic conduit for food and helps prevent aspiration. As the food bolus is propelled past the epiglottis, contraction of the constrictor muscles propels the food toward the cricopharyngeus. The cricopharyngeus relaxes as the

CHAPTER 22

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FIG 22-27 Normal hypopharynx. A, Axial postcontrast CT image shows piriform sinus (PS) lateral to aryepiglottic fold (*). B, Similar structures are seen on axial postcontrast fat-saturated T1-weighted image. C, The postcricoid region is delineated by arrows on this axial postcontrast CT image. D, Axial postcontrast T1-weighted image shows postcricoid region (white arrows) and posterior pharyngeal wall (black arrows).

food enters the esophagus, where peristaltic action propels the food to the stomach. Congenital and inlammatory lesions of the hypopharynx will be discussed here, whereas hypopharyngeal tumors are covered along with the larynx.

Congenital and Inlammatory Lesions Branchial Apparatus Anomalies. During embryologic development, the tissues of the neck are derived from branchial arches that are separated externally by grooves and internally by pharyngeal pouches. Incomplete or aberrant fusion of two adjacent arches can result in the formation of branchial cleft anomalies that include cysts, istulas, and

sinuses. The majority of branchial apparatus anomalies are cysts, which can originate from the branchial cleft, branchial arch, or pharyngeal pouch remnant. Therefore branchial apparatus cyst is the preferred terminology and is synonymous with branchial cleft cyst (BCC).55 BCC typically presents in children from 10 years of age to adults aged 30-40 years.46 BCCs are categorized into three types by their embryologic development. First branchial apparatus anomaly. First BCC develops from the irst branchial arch, which extends from the external auditory canal (EAC) through the parotid gland to the submandibular space. The most common location of irst BCC is inferior/posterior to the EAC or in the parotid gland.

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Second branchial cleft cyst. Second BCC is the most common branchial cleft anomaly.46 The most common presentation is presence of a painless luctuant mass or recurrent inlammation-infection in the submandibular space at angle of the jaw. The classic radiologic appearance of second BCC is that of a well-deined, usually unilocular cyst that shows a predilection for the angle of the jaw, along the anterior margin of sternocleidomastoid muscle, behind the submandibular gland, and lateral to the carotid sheath structures. Varying embryologic development results in other locations for BCC-II: (1) supericial to sternocleidomastoid muscle, (2) medial to the sternocleidomastoid muscle and lateral to the carotid, with a characteristic beak between the common carotid artery bifurcation toward the pharynx, and (3) in the pharyngeal mucosa.46 Third and fourth branchial cleft cysts. Third BCCs are located in the posterior cervical space posterior to the common or internal carotid artery and the sternocleidomastoid muscle. They may present as a istula along the anterior border of sternocleidomastoid. The tract passes posterior to the common carotid artery and enters the thyroid membrane to reach the pharynx at the pyriform sinus. Despite its rarity, third BCC is the second most common congenital cystic lesion in the posterior triangle, after cystic hygromas, which are the most common lesions of this space.46,55 Fourth branchial cleft anomalies are generally sinus tracts or istulae and arise from the pyriform sinus, pierce the thyrohyoid membrane, and descend along the tracheoesophageal groove along the course of the recurrent laryngeal nerve.46,55 Both anomalies may have istulous communication from the pyriform sinus through the thyrohyoid membrane into the neck. These anomalies are much less common than second BCC and lymphatic malformation. However, when recurrent neck infection occurs lateral to the pyriform sinus and/or along the tracheoesophageal groove without risk factors or clearly deined etiology, the presence of third or fourth branchial cleft istula should be suspected. A luoroscopic barium swallow exam is valuable to demonstrate the istula for complete surgical excision in these cases.

Miscellaneous Tortuous ICA. The internal carotid artery may have a medial course in the retropharyngeal region. This may be unilateral or bilateral (Fig. 22-28). When bilateral, these are called kissing carotids. When seen in children, this represents persistent fetal angulation of carotids. In adults this is usually a manifestation of atherosclerotic changes causing ectasia and tortuosity. Patients are usually asymptomatic, and this is an incidental inding on imaging studies. However, some patients may present with a pulsatile retropharyngeal mass. Diagnosis is important because this condition is a potential risk for pharyngeal surgery and may result in catastrophic bleeding. Therefore, diagnosis prior to imaging prevents iatrogenic bleeding.

Pharyngocele. Pharyngocele or lateral pharyngeal diverticulum refers to lateral pharyngeal bulging through one of the weak areas of lateral pharyngeal wall. A true pharyngocele is herniation of pharyngeal mucosa beyond the thyrohyoid membrane. Congenital pharyngoceles are branchial cleft sinus tracts that connect internally with the pharynx. Acquired pharyngoceles are pulsion-type diverticula. These arise from the posterior faucial pillar and pyriform fossa and are caused by chronically raised intrapharyngeal pressure accompanied by loss of muscular tone. The diagnosis is generally made by barium swallow studies. Differential diagnosis includes Zenker’s diverticulum, laryngocele, esophageal diverticulum, cricopharyngeal spasm, foreign body, neurologic disease, myopathies, and globus hystericus. Surgery is indicated if the patient is symptomatic.

FIG 22-28 Tortuous internal carotid arteries (ICAs). Axial postcontrast CT image shows right ICA extending into retropharyngeal space (white arrow) while the left ICA is also medial in location (black arrow).

Diverticula/Fistulae. Zenker’s diverticulum is a pulsion-type diverticulum, a mucosa-lined outpouching from the hypopharynx just proximal to the upper esophageal sphincter. It is a false diverticulum because it does not contain all layers of the pharyngeal wall. It arises from the dehiscence of Killian, a site of focal weakness in the cleavage plane between the circular and oblique ibers of the cricopharyngeus. Most patients are elderly, in the seventh or eighth decade of life. A barium swallow study can depict an outpouching during swallowing, best seen on the lateral view in the posterior midline at the C5-C6 level. Killian Jamieson diverticulum is a true diverticulum that is located just below the cricopharyngeus muscle and is situated anteriorly and laterally. These are usually smaller than Zenker’s diverticulum and less often symptomatic.

Dermoid. Pharyngeal dermoids are choristiomatous developmental anomalies arising from the irst branchial cleft area. These are epithelial inclusion cysts resulting from faulty separation of ectoderm from neuroectoderm. Dermoids usually present in the second and third decades of life. On CT these appear as low-density cystic nonenhancing structures in the midline. Fat, mixed luid density, and calciication may also be seen. On MRI, these lesions are usually hyperintense on both T1- and T2-weighted images and do not demonstrate restricted diffusion. The imaging features are usually pathognomonic. In the pharynx, these lesions can present with airway obstruction and breathing dificulties.

Amyloid. Amyloidosis is a diverse group of disorders of uncertain etiology. The disease is characterized pathologically by abnormal protein deposition in the extracellular tissue. Within the aerodigestive tract, amyloid preferentially involves the tracheobronchial airway. Involvement of the pharynx by amyloidosis is exceedingly rare. The

CHAPTER 22 disease can be classiied as systemic or localized. Localized disease involves only one organ and has a better prognosis, whereas systemic disease involves multiple organs and has a poorer prognosis. MRI is the technique of choice to demonstrate features of amyloidosis. Amyloid deposits appear isointense on T1-weighted and hypointense on T2-weighted sequences.29

Drugs/Cocaine. In patients with heavy nasal cocaine abuse, there are reports describing an aggressive intranasal and intrapharyngeal destructive process simulating Wegener’s granulomatosis and midline reticulosis.22 Prominent nasopharyngeal and oropharyngeal ulcers have been reported in these cases, which improve on abstinence from cocaine abuse.

Trauma Traumatic injury to the pharynx is usually seen with direct trauma, instrumentation such as endoscopy, or following ingestion of ish or chicken bones. This may result in disruption of pharyngeal walls and formation of a retropharyngeal abscess. Plain radiographs may demonstrate widening of the prevertebral space and air in the mediastinum or neck. CT can more accurately depict the extent of injury and assess any complications of the injury, such as retropharyngeal abscess, mediastinitis, and septic thrombosis of the internal jugular vein. CT is also useful for localization of foreign bodies and aids in management of these cases.

POSTTHERAPEUTIC NECK The management of head and neck cancer involves multidisciplinary evaluation and treatment, including surgery, radiation therapy, and chemotherapy. A multitude of surgical approaches with or without tissue reconstruction, different types of neck dissection, a variety of

Pharynx

radiation therapy techniques, and concurrent and neoadjuvant chemotherapy regimens may complicate imaging indings in the posttherapeutic setting. Knowledge of common surgical procedures and their expected postoperative appearances is vital to avoid falsepositive interpretations. An array of advanced biological imaging techniques such as MR spectroscopy, CT perfusion, MRI diffusion and perfusion, and FDG-PET may prove useful in this regard, insofar as they have the ability to look beyond size, morphology, and enhancement and can focus on the molecular-level differences between active tumor and benign tissue.69 This section will review the common postsurgical appearances after various types of neck dissection, reconstructive techniques, postradiation changes, complications, and a brief discussion on the role of advanced imaging in posttreatment neck evaluation.

Neck Dissection The three major types of neck dissection are radical neck dissection (RND), modiied radical neck dissection (MRND), and selective neck dissection (SND). RND is the gold standard by which all other neck dissections are compared. It involves en bloc removal of all the ipsilateral lymph nodes (LN) (levels I-V) and includes the sternocleidomastoid muscle (SCM), internal jugular vein (IJV), submandibular gland (SMG), and spinal accessory nerve (SAN)48,77 (Fig. 22-29A). Indications for RND are extensive cervical involvement or lymph nodes with gross extracapsular spread and invasion into the adjacent tissues. MRND is the same as RND but with preservation of one or more of the nonlymphatic structures (SCM, SAN, SMG, and IJV) (see Fig. 22-29B). MRND is indicated in patients with less spread and invasion and has some advantages; for example, preservation of the SAN prevents development of frozen shoulder (adhesive capsulitis) and causes less cosmetic deformity than RND.63

*

* IJV SCM

*

SCM

+ A

B

677

C

FIG 22-29 Neck dissections. A, The submandibular gland (arrow), internal jugular vein (IJV) and sternocleidomastoid muscle (SCM) are present on the right but absent in the left neck after radical neck dissection (RND). There has also been resection of much of the fat in the left neck. B, Modiied RND. There is absence of the left submandibular gland (white *), with normal gland seen on the right (arrow). The SCM and IJV (arrow on left) are preserved. There is diminished fat volume deep to (white *) and posterior (+) to the SCM muscle, which is removed along with nodes at levels I-V. C, Posterolateral neck dissection. There is diminished fat volume deep to (arrow in front) and posterior to (arrow behind) to the SCM muscle. The submandibular gland (*) is preserved.

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TABLE 22-1 Typical Postoperative Appearance After Neck Dissections

BOX 22-2

Type of Neck Dissection

Pedicle • Rotated regional skin and muscle • Preserved vascular pedicle • Preserved nutrient feeders • Preferred for closing defects in irradiated necks

RND

Extended RND

Supraomohyoid SND

Lateral SND

Postoperative Appearance Absence of: • Level I-V LN • SMG • IJV • SCM RND plus: • Level VI and/or VII lymph node dissections • Retropharyngeal LN dissection, and/or • Internal carotid artery, hypoglossal nerve, and vagus nerve • Level I-III dissection • Absence of right SMG • Preserved right SCM and IJV • Level II-IV dissection • Preserved SCM and IJV

IJV, internal jugular vein; LN, lymph nodes; RND, radical neck dissection; SCM, sternocleidomastoid; SMG, submandibular gland; SND, selective neck dissection.

SND has four common subtypes: the supraomohyoid type (levels I-III and ipsilateral SMG), the lateral type (levels II-IV), the posterolateral type (levels II-V as well as posterior auricular and suboccipital LN) (see Fig. 22-29C), and the anterior type (levels VI and VII, typically bilateral). SND has the advantage that it preserves the functional and cosmetically relevant structures. Extended radical neck dissection is the same as RND but includes removal of additional nodes (levels VI and VII), retropharyngeal LN dissection, and/or nonlymphatic structures such as the internal carotid artery, hypoglossal nerve, and vagus nerve. The typical CT and MRI appearance after neck dissections is summarized in Table 22-1. Note that it may be very dificult to determine that surgery has been performed after SND, and careful correlation with clinical history and surgical notes is mandatory.

Surgery with Reconstruction Curative surgical resection requires a wide local excision to obtain negative margins; however, given the anatomic complexity of the head and neck, complex reconstructive techniques are often required to close the defect and maintain cosmesis and function (Fig. 22-30). Various reconstructive techniques have been introduced to close the surgical defect, and these techniques are mainly classiied into three types as outlined in Box 22-2.

Postradiation Changes Radiation therapy for head and neck cancer is classiied into two types: external beam radiation therapy and brachytherapy. External beam radiation therapy includes 3D conformal radiation therapy, intensitymodulated radiation therapy, and stereotactic radiosurgery.5 External beam radiation therapy uses photon, electron beam, or proton beam radiation delivered from a source external to the patient. Brachytherapy uses radioactive sources such as iodine seeds, iridium, or cesium, which are implanted in the patient. Deinitive doses of radiation with external beam radiation therapy for head and neck cancer consist of 66 to 70 Gy delivered daily during a period of 7 weeks. In the past 10 years, intensity-modulated radiation therapy has become the favored

Surgical Reconstruction

Techniques

Free Flap • Transferred from distant sites to the surgical ield • Skin, soft tissue, muscle, bone, and bowel • No vascular pedicle • Microvascular techniques are employed Prosthesis • Wide spectrum of material and techniques • Maxillofacial and craniofacial • Improved cosmesis and function

technique for administering photon external beam radiation therapy to patients with head and neck cancer, because it allows sparing of multiple organs at risk, including the bilateral parotid glands, pharyngeal constrictor muscles, and optic structures, and also allows better coverage of the tumor. Changes after radiation therapy are commonly divided into early and late reactions. CT and MRI indings of early postradiation changes include thickening of the skin and platysma, reticulation of the subcutaneous fat, edema and luid in the retropharyngeal space, increased enhancement of the major salivary glands, thickening and increased enhancement of the pharyngeal walls, and thickening of the laryngeal structures (Fig. 22-31). Late reactions to radiation therapy include atrophy of the salivary glands and thickening of the pharyngeal constrictor muscles, platysma, and skin.79

Complications of Therapy These can be divided into complications after surgery, osseous complications, vascular complications, and radiation-induced complications, as summarized in Table 22-2.

Imaging Appearances of Tumor Recurrence The most common locations for tumor recurrence are in the operative bed and at the margins of the surgical site. Tumors typically recur within the irst 2 years after treatment. Early recurrence within weeks after surgery—before adjuvant radiation therapy—is sometimes seen because of accelerated repopulation. Tumor recurrence is identiied as an expansile lesion in the operative bed or as progressive thickening of soft tissues deep to the lap.10,37,41,63 CT demonstrates recurrence as an iniltrating slightly hyperattenuating enhancing mass, with or without bone destruction10,37,63 (Fig. 22-32). Tumor recurrence has attenuation similar to that of muscle. Therefore if a suspected mass has lower attenuation than that of muscle, it is unlikely to be a malignancy and often is related to edema.77 MRI demonstrates tumor recurrence as an iniltrative mass with intermediate T1-weighted signal intensity, intermediate to high T2weighted signal intensity, and postcontrast enhancement. The differential diagnosis for tumor recurrence includes a vascularized scar, which represents early ibrosis.48 Fundamental tenets for the evaluation of tumor recurrence include careful utilization of comparison scans, with a high index of suspicion

CHAPTER 22

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* A

C

D

B FIG 22-30 Surgical reconstruction. A and B, Pectoralis major myocutaneous pedicle lap (arrows) is seen along anterior neck on postcontrast axial CT image (A) and reformatted sagittal image (B) and was used to ill defect of loor of mouth and neck following multiple surgeries for recurrent ameloblastoma. C, Postcontrast coronal reformatted CT image shows rectus abdominis myocutaneous free lap (*) illing the defect in oral cavity and masticator space following anterior two-thirds glossectomy and composite resection for recurrent tongue cancer invading the mandible. D, Fibular free tissue transfer (arrows) was used to reconstruct mandible.

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* *

A

B FIG 22-31 Postradiation changes. A, Axial postcontrast CT image shows thickening of platysma muscles (arrows) and reticulation of subcutaneous fat. B, Axial postcontrast CT image shows diffuse thickening of the epiglottis (*).

A

B FIG 22-32 Recurrent disease in a patient with piriform sinus cancer status post total laryngopharyngectomy with anterolateral thigh free lap. A, Axial postcontrast CT image shows a mass (arrows) near the lower end of lap. B, Sagittal reformatted postcontrast CT image shows the recurrent mass (arrows) just superior to the tracheostomy and tracheoesophageal puncture.

CHAPTER 22

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681

B

A

FIG 22-33 Physiologic imaging. A, Axial postcontrast CT image shows mass along right upper margin of anterolateral thigh free lap (arrows), of concern for recurrence in a patient status post total laryngopharyngectomy for recurrent hypopharyngeal cancer. B, PET-CT shows hypermetabolism in mass of concern on CT (arrow on right). There is also hypermetabolism along left side of lap, compatible with recurrence (arrow) not suspected on CT.

TABLE 22-2 Infection

Vascular

Radionecrosis

Chylous istula

• • • • • • • •

Neuroma

• • •

Dermal seeding

•

Other

• • • • •

Complications of Therapy Cellulitis Phlegmon Abscess IJV thrombosis Arterial injury Radiation arteritis Can occur in native and grafted bone Imaging indings of osteoradionecrosis: 1. Cortical disruption 2. Rarefaction 3. Sequestration 4. Pathologic fracture 5. Diffuse soft tissue thickening Usually occurs after a level IV LN dissection Appears as a persistent luid collection Rare proliferative reparative response to transected peripheral nerves; not a true neoplasm Most commonly occurs in patients with extracapsular spread of disease or in immunocompromised patients Tissue ibrosis Delayed central nervous system reaction Radiation myelopathy Cranial nerve palsy Secondary tumors

IJV, internal jugular vein; LN, lymph nodes.

for any enlarging mass or new lymphadenopathy, which should be considered a recurrence unless proven otherwise.

ADVANCED BIOLOGICAL IMAGING TECHNIQUES The traditional role of imaging has remained in the anatomic domain, but recent advanced imaging techniques such as MR spectroscopy, MRI diffusion and perfusion, CT perfusion, and FDG-PET provide information about cellularity, perfusion, neoangiogenesis, and metabolism and hold promise in assessment of pharyngeal cancers. These techniques are useful in monitoring tumor response during chemoradiation, assessing response at the end of therapy, and detecting residual or recurrent disease and metastasis (Fig. 22-33). Information that can be obtained with these techniques will help propel us toward customization of treatments and better prognostication for patients in this era of personalized medicine.78

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23 Paranasal Sinuses Varsha Joshi, Rima Sansi, Saugata Sen, and Piyush Saxena

IMAGING OPTIONS AND PROTOCOLS Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary imaging modalities for assessment of the paranasal sinuses. Both these imaging techniques are far superior to plain radiographs in the evaluation of the sinonasal cavities. Plain radiographs of the paranasal sinuses are limited in their ability to delineate the complex bony anatomy or to characterize sinonasal disease and hence are almost obsolete today. They also suffer from high false-negative results.

CT CT scan is the primary imaging modality for evaluation of sinonasal disease. The concept of screening sinus CT (SSCT) performed in the coronal plane with single window settings, 3-mm sections, and without administration of contrast was promoted in the early 1990s when functional endoscopic sinus surgery (FESS) became popular among endoscopic surgeons. With the evolution of CT scanners to multidetector (MD) CT technology, direct coronal acquisition is no longer commonly performed. Today sinus CT is performed in the axial plane with the patient supine on the scanning table and neutral position of the gantry using 0.625-mm collimation. The volumetric dataset is then reconstructed in coronal, axial, and sagittal planes to provide up to 0.9-mm-thick images in bone (width 3500, center 500) and soft tissue (width 270, center 70) algorithms. When a contrast CT is required, 3- to 4-mm-thick slices are generated in soft tissue algorithm.

MRI MRI of the paranasal sinuses is performed using a head and neck coil. The protocol includes nonenhanced high-resolution 3- to 4-mm T1- and T2-weighted images, diffusion-weighted imaging (DWI), and contrast-enhanced T1-weighted images with fat suppression. Axial and coronal planes are preferred, and sagittal sequences may be performed when required. Care must be taken to include the adjacent orbits and intracranial cavity along with the sinuses.

ANATOMY Nose, Nasal Cavity, and Lateral Nasal Wall The nose implies the external nose that projects anteriorly from the face. It consists of a bony portion superiorly and a cartilaginous portion inferiorly. The anatomic subunits of the nose include the nasal root, dorsum, side walls, and nasal septum. The nasal septum is the midline partition that separates the right and left side of the nose and is made up of the septal (quadrangular) cartilage anteriorly, the perpendicular plate of the ethmoid bone posterosuperiorly, and the vomer posteroinferiorly. The external nose leads posteriorly into the nasal cavity, which in turn leads posteriorly into the nasopharynx.

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The lateral wall of the nasal cavity shows three (sometimes four) constant projections—the superior, middle, and inferior turbinates— that divide the lateral nasal wall into three meati lateral to the turbinates—the superior, middle, and inferior meati, respectively. A fourth turbinate (supreme turbinate) may be present, and the supreme meatus is the space above the superior turbinate and lateral to the supreme turbinate. The turbinates and meati are best seen on coronal CT sections (Fig. 23-1). The middle turbinate and meatus form the most important anatomic area in the lateral wall of the nose. The attachments of the middle turbinate have anatomic and surgical relevance and provide fairly good stability to the turbinate. Anteriorly the turbinate runs in the sagittal plane and attaches superiorly to the cribriform plate (see Fig. 23-1). As it continues behind, it turns laterally into the coronal plane and attaches to the lamina papyracea to form the basal lamella that divides the ethmoid cells into the anterior and posterior ethmoid cells. The middle meatus contains the drainage pathways of the anterior ethmoid air cells, the maxillary and frontal sinuses (osteomeatal unit [OMU]). This region is most commonly involved in the pathophysiology of chronic rhinosinusitis and will be described in greater detail in the following sections.

Paranasal Sinuses There are four paired paranasal sinuses, one on either side of the midline. They develop from ridges in the lateral nasal wall by the eighth week of embryogenesis and continue pneumatization until early adulthood. Each sinus is named after the bone in which it is located. The relevant imaging anatomy is described in the following sections.4,5,57,62,75

Maxillary Sinus. Each maxillary sinus is located within the maxillary bone and is the largest and most constant paranasal sinus. It is present at birth and shows a bimodal growth pattern between ages 1 and 3 and 7 and 18 years. The roof of the sinus is formed by the loor of the orbit and has a canal for the second branch of ifth cranial nerve (see Fig. 23-1). The medial wall is formed by portions of the ethmoid, palatine, and lacrimal bones. A fairly large part of the medial wall, however, does not contain any bone and is formed by connective tissue and sinus mucosa. This membranous area is called the fontanelle and can break down secondary to sinus infection, forming an accessory ostium of the sinus. The accessory ostium is nonfunctional and drains the sinus only when the main ostium is blocked. The primary maxillary sinus ostium is located on the highest part of the medial wall of the maxillary sinus (see Fig. 23-1). The loor of the sinus is formed by the alveolar process of the maxilla and palatine bones. The posterolateral wall separates it from the pterygomaxillary issure medially and infratemporal fossa laterally (see Fig. 23-23A, B, and D). The maxillary sinus drains through the primary ostium into the ethmoid infundibulum (see Fig. 23-1).

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thick anterior table, and the posterior wall is the thinner posterior table that separates the sinus from the cranial cavity. The loor is the anterior roof of the orbit. The frontal sinus drains through the frontal sinus ostium and the frontal recess into the middle meatus (see Fig. 23-2).

Sphenoid Sinus. The sphenoid sinus is located in the body of the

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sphenoid. It begins to grow at age 3 and is fully pneumatized by about age 18. The sphenoid sinuses on the two sides are separated by the intersphenoid septum. The roof of the sinus is formed by the sellar loor, and the lateral wall demarcates the sinus from the cranial cavity. The carotid artery is situated in the lateral wall, the optic nerve superolateral to the sinus, and the vidian nerve canal in its loor (see Fig. 23-5A). The sphenoid sinus ostium is located medially in the anterosuperior portion of the sinus and opens into the sphenoethmoid recess (Fig. 23-3).

FIG 23-1 Coronal CT image through the osteomeatal unit. Normal

Drainage Pathways of the Paranasal Sinuses

anatomy is depicted on the left side. Note the uncinate process (elbow arrow), ethmoid infundibulum (dotted line), hiatus semilunaris (curved line), ethmoid bulla (B), frontal recess (dashed line), maxillary sinus (MS) ostium (white circle), middle meatus (double line), Kero’s type I ethmoid roof on left and type II ethmoid roof on right (vertical white arrows), and fovea ethmoidales forming the roof of the ethmoid cells (vertical white arrowheads). Also seen are the infraorbital foramen in the roof of the maxillary sinus, inferior turbinate (IT), middle turbinate (MT), lamina papyracea (horizontal white arrowheads), and the opening of the anterior ethmoid artery (horizontal black arrow). The middle turbinate is seen attaching superiorly to the cribriform plate. Note the infundibular pattern of sinonasal disease on the right side, with opaciied maxillary sinus and infundibulum (curved white arrow).

The paranasal sinuses are broadly divided into two major groups: the anterior sinuses and the posterior sinuses. The anterior sinuses comprise the frontal sinus, anterior ethmoid air cells, and maxillary sinus. These drain into a common area centered in the middle meatus, the osteomeatal unit (OMU). The posterior sinuses are the posterior ethmoid air cells and the sphenoid sinuses. These drain into the sphenoethmoid recess.

Ethmoid Sinus (Ethmoid Air Cells). Each ethmoid sinus is located within the ethmoid labyrinth and has a honeycomb appearance. It is present at birth and continues to grow until about 12 years of age. The ethmoid labyrinth is situated inferolateral to the olfactory fossa, which is bounded by the horizontal and vertical lamellae of the cribriform plate. The roof of the sinus is formed by the fovea ethmoidales of the frontal bone, which joins the vertical lamella of the cribriform plate (see Fig. 23-1). The medial wall is formed by the lateral surface of the middle and superior turbinate, the lateral wall by the lamina papyracea (see Fig. 23-1), and the posterior wall by the anterior wall of the sphenoid sinus (Fig. 23-2). The ethmoid sinus is divided into multiple discrete cells by bony lamellae that extend laterally to the lamina papyracea and superiorly to the fovea ethmoidales. Of these, the basal lamella divides the ethmoid air cells into anterior and posterior groups of ethmoid cells. The anterior ethmoid air cells drain into the ethmoid infundibulum, and the posterior ethmoid air cells drain into the superior meatus (see Figs. 23-1 and 23-2). The pneumatization of the ethmoid air cells shows the highest variation among all the sinuses. There are two primary types of ethmoid air cells: intramural and extramural. Intramural cells remain within the ethmoid bone and include the ethmoid bulla, suprabullar cell, and frontal bullar cell. The extramural cells develop external to the ethmoid labyrinth and include the agger nasi cell, frontal cell, supraorbital ethmoid cell, Haller cell, and Onodi cell. These are considered separately in the section on anatomic variants.

Frontal Sinus. Each frontal sinus lies within the frontal bone. The frontal sinus is rudimentary at birth and begins to grow by age 6, continuing until the late teens. The frontal sinuses on two sides are separated by the interfrontal sinus septum. The anterior wall is the

Osteomeatal Unit. The OMU is the common drainage pathway of the anterior sinuses, the key area in the pathophysiology of chronic sinusitis and the center of interest since the advent of FESS. It is a narrow anatomic region bounded by the middle turbinate medially, the lamina papyracea laterally, and the basal lamella posteriorly. This region and all its components are best visualized on coronal CT sections (see Fig. 23-1). The OMU comprises the uncinate process, hiatus semilunaris, ethmoid infundibulum, and the ethmoid bulla (bulla ethmoidales). The uncinate process is a key component of the osteomeatal unit and a very important surgical landmark for endoscopic sinus surgery. It is a hook-shaped bone that arises from the posteromedial wall of the nasolacrimal duct and is best seen on coronal CT sections as the superior extension of the medial wall of the maxillary sinus (see Fig. 23-1). The maxillary sinus ostium is located behind the uncinate process. The hiatus semilunaris is a crescent-shaped cleft located just posterior and superior to the uncinate process and anteroinferior to the ethmoid infundibulum (see Fig. 23-1). It serves as the communication of the ethmoid infundibulum with the middle meatus. The ethmoid infundibulum receives drainage from the ethmoid bulla in its anterior portion and the maxillary sinus ostium in its loor. It opens into the hiatus semilunaris and is located inferomedial to the ethmoid bulla and superolateral to the uncinate process (see Fig. 23-1). The ethmoid bulla is the largest and most constant of the anterior ethmoid air cells. It receives drainage from the anterior ethmoid air cells and drains into the ethmoid infundibulum. There may be variation in the amount of pneumatization of the ethmoid bulla. If it is not pneumatized, it is termed torus ethmoidales; excessive pneumatization may form a giant bulla that may ill the entire middle meatus. The ethmoid bulla is located just posterior and superior to the hiatus semilunaris and posterior to the frontal recess. The lateral wall is formed by the lamina papyracea, the roof by the skull base, and the posterior wall by the basal lamella (see Figs. 23-1 and 23-2). Sometimes an air recess may form between the bulla and the basal lamella; this is called a retrobullar recess or sinus lateralis.

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FIG 23-2 Sagittal CT image through the frontal sinus drainage pathway. Frontal sinus (FS) narrows down to the frontal sinus ostium at the level of the nasofrontal spine (black arrow) and then the frontal recess (dashed white line). Agger nasi cell (A) and type I frontal cell (elbow black arrow) are seen anterior to the frontal recess, and suprabullar cell (SB) and bulla ethmoidales (B) are seen posteriorly draining into the infundibulum (dash-dot line). Note the posterior ethmoid air cells (PE) draining into the superior meatus (white line). The posterior wall of the ethmoid air cells is formed by the anterior wall of the sphenoid sinus.

frontal sinus drainage pathway (FSDP) comprises the frontal sinus infundibulum, frontal sinus ostium (FSO), and frontal recess (FR).29,36,44 Only the FR is a part of the OMU. The entire anatomy of the FSDP is best seen on coronal and sagittal images. The frontal sinus tapers down to a funnel-shaped inferior portion called the frontal sinus infundibulum. This frontal infundibulum leads to the FSO, which is the narrowest part of the FSDP and located in its most dependent portion in the loor of the sinus at the level of the nasofrontal spine (see Fig. 23-2). The frontal infundibulum and the FSO are best visualized on sagittal images. The portion of the FSDP below the ostium is the FR, and this drains into the middle meatus (see Fig. 23-2). It measures about 13 mm in anterior-to-posterior dimension and has the shape of an inverted funnel with its tip at the frontal ostium. The FR is surrounded by the ethmoid air cells—the agger nasi cell anteriorly, the ethmoid bulla posteriorly and laterally, and the most anterior and superior portion of the middle turbinate medially (see Figs. 23-1 and 23-2).

Sphenoethmoid Recess. The sphenoid sinus ostium opens into the sphenoethmoid recess (SER). The SER lies just lateral to the posterosuperior nasal septum and behind the tail of the superior turbinate and is best appreciated on sagittal and axial CT images (see Fig. 23-3). The posterior ethmoid air cells drain into the superior meatus and from there into the SER (see Fig. 23-2).

IMPORTANT ANATOMIC VARIATIONS AND THEIR RELEVANCE Numerous variations in the sinonasal anatomy have been described. Many of them have important clinical and surgical relevance, and

FS FB

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B FIG 23-3 A, Axial CT image shows the sphenoid sinus ostia (arrows). B, Sagittal image shows the sphenoid sinus ostium (arrow) leading into the sphenoethmoid recess (dashed line). Note the frontal bullar cell (FB) protruding into the frontal sinus (FS) posteriorly.

CHAPTER 23 it is very important to identify them on the presurgical scans obtained in such patients.4,5,57,65 MDCT with its multiplanar reformations provides the best details of the complex bony anatomy and anatomic variants of the sinonasal cavities. It is extremely important to review the CT images in all three planes for better understanding of the anatomy and identiication of these anatomic variations. If available, review of images on a workstation is extremely beneicial for reporting the scans.

Frontal Recess Cells These cells are variations in the pneumatization of the anterior ethmoid air cells. They are broadly divided into the anterior and posterior groups of frontal recess cells. The anterior group is located anterior to the frontal recess and comprises the agger nasi cells and the frontal cells. The posterior frontal cells are located posterior to the frontal recess and include the supraorbital cells, frontal bullar cells, and suprabullar cells; they are bordered posteriorly or superiorly by the base of the skull.29,36,44 These cells may obstruct frontal sinus drainage at the level of the frontal recess and contribute to the development of frontal sinusitis. Also, if these cells are not addressed during endoscopic surgery on the frontal recess, they often lead to surgical failure and recurrence of the disease process. Therefore it is very important for the radiologist to identify them and comment on their presence using the standard nomenclature as described below.

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Frontal Cells (Kuhn’s Cells). Four types of frontal cells are described.29,44,45 Types 1 to 3 frontal cells are commoner and located directly above the ANC. The type I cell is a single anterior ethmoid air cell seen above the ANC (see Fig. 23-2). Type II cells are two or more anterior ethmoid air cells above the ANC (see Fig. 23-3). The type III cell is a single large cell above the ANC that bulges into the frontal sinus. The type IV cell is an isolated air cell located completely within the frontal sinus, simulating a “cell within a cell” appearance; it is visualized infrequently (see Fig. 23-3).

Supraorbital Ethmoid Cell. This cell represents pneumatization of the orbital plate of the frontal bone posterior to the frontal recess and the frontal sinus.27,34,54 It simulates the appearance of septate or hyperpneumatized frontal sinuses on coronal images, and axial images conirm their location posterior and lateral to the frontal sinus (see Fig. 23-14).

Frontal Bullar Cell and Suprabullar Cell. The ethmoid bulla forms the posterior boundary of the frontal recess. The frontal bullar cell, if present, lies above the ethmoid bulla and posterior to the frontal sinus and frontal recess.24,34,54 It extends into the frontal sinus and is best seen on sagittal images (see Fig. 23-3B). When the cell lies below the level of the frontal sinus ostium and does not extend into the frontal sinus, it is called a suprabullar cell (see Fig. 23-2).

Agger Nasi Cell. The agger nasi cell (ANC) is a fairly constant ante-

Onodi Cell (Sphenoethmoid Cell)

riormost ethmoid cell seen in up to 98% patients at CT. It is located anterior to the vertical attachment of the middle turbinate and is best visualized on sagittal and coronal CT sections (Fig. 23-4; also see Fig. 23-2). The degree of pneumatization of the ANC varies and has a bearing on the size of the frontal sinus ostium and frontal recess.6

The Onodi cell is an anatomic variation of the most posterior ethmoid air cell when it extends into the sphenoid bone, superior or superolateral to the sphenoid sinus, pushing the sphenoid sinus inferiorly. The cell is intimately related to the optic nerve canal and can be mistaken for sphenoid sinus at endoscopy, increasing the risk of orbital

FS FS

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FIG 23-4 Sagittal CT images through the frontal sinuses (FS) shows the types of frontal cells located atop the agger nasi cell (A). Type II frontal cells (arrowhead), type III frontal cell (curved arrow), type IV frontal cell (straight arrow).

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FIG 23-5 Coronal CT images at the level of the sphenoid sinus (SS). A, The hyperpneumatized SS, pneumatization of the anterior clinoid processes (A), type III optic canals (black arrows), foramen rotundum (white arrows), and vidian nerve canal (elbow arrows). Note the intersphenoid septum attaching to the right optic canal (white arrowhead). B, Bilateral Onodi cells (ON) with type IV optic canals (black arrows). Note the mucosal disease in the right sphenoid sinus (dashed black arrow).

complications. Hence it is of paramount importance to report their presence at CT examinations. Identiication of this cell requires careful review of coronal, axial, and parasagittal CT images.27 Presence of a horizontal septum dividing the sphenoid sinuses into “two loors” or giving a cruciform appearance on coronal CT images suggests the presence of Onodi cells4,24,34 (Fig. 23-5).

Haller Cell (Orbitomaxillary Or Infraorbital Ethmoid Cell)

C

This is an extramural anterior ethmoid cell that pneumatizes inferior to the orbital loor, extending from the ethmoid labyrinth below the ethmoid bulla toward the interior of the maxillary sinus (Fig. 23-6). Although debate exists on whether or not their presence contributes to the occurrence of sinusitis, most agree that it is their number and size that inluence the development of inlammatory sinus disease.7,67

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Uncinate Process Variations

FIG 23-6 Coronal CT image shows Haller cells on left side (arrow-

Three types of uncinate processes have been described, depending on the superior attachment that impacts the drainage of the frontal sinus.34,54,57,62 Type I uncinate process is the commonest type and attaches to the lamina papyracea, separating the ethmoidal infundibulum and the frontal recess (Fig. 23-7). Type II uncinate attaches to the skull base, and type III turns medially and attaches to the middle turbinate (see Fig. 23-7). In type II and III uncinate processes, the frontal recess opens into the ethmoid infundibulum. The uncinate process may also be medialized or lateralized. An uncinate bulla may be seen.

heads), paradoxical curvature of the middle turbinates (MT), nasal septal deviation to the right side with a bony septal spur (curved arrow), and lamellar concha on either side (C). Hypertrophy of the left inferior turbinate (IT) is noted.

Nasal Septal Variations The nasal septum may be deviated and make endoscopic access dificult. The deviation may be focal or more of a smooth curvature and is often associated with septal spurs and a concha bullosa or a lamellar concha (see Fig. 23-6). A nasal septal air cell may be seen in the posterosuperior portion of the nasal septum and may communicate with the sphenoid sinus.

Middle Turbinate Variations The middle turbinate may be pneumatized. When pneumatization involves the bulbous portion of the middle turbinate, it is termed concha bullosa. If only the attachment portion of the middle turbinate is pneumatized, it is termed lamellar concha (see Fig. 23-6). A small concha may not be clinically signiicant, but a larger one—commonly associated with a nasal septal deviation—may obstruct the ethmoid infundibulum and lead to sinusitis.7 The convexity of the middle turbinate may be directed laterally and is called paradoxical curvature of the turbinate (see Fig. 23-6). A small paradoxical turbinate may not be signiicant, but a larger one may impair drainage at the OMU.7

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Other Variants The maxillary sinus may show septations, resulting in inadequate drainage of sinus secretions. An accessory ostium may be present. The importance of this lies in the fact that an antrochoanal polyp may sometimes exit through the accessory ostium rather than the natural ostium. An aerated crista galli may communicate with the frontal recess, causing obstruction of the ostium and leading to chronic sinusitis.

INFLAMMATORY SINONASAL DISEASE—SINUSITIS

FIG 23-7 Coronal CT image shows the attachments of the uncinate processes (arrowheads). Type I uncinate on the left side attaches to lamina papyracea and the frontal recess (thin dotted line) opens into the middle meatus. Type III uncinate on the right side attaches to the middle turbinate, and the frontal recess (thick dotted line) opens into the ethmoid infundibulum.

Variations of the Ethmoid Roof Kero’s classiication describes three types of ethmoid roofs, depending on the depth of the olfactory fossa, determined by measuring the height of the lateral lamella of the cribriform plate. Type I ethmoid roof has a depth of 1 to 3 mm, type II a depth of 4 to 7 mm, and type III a depth of 8 to 16 mm (see Fig. 23-1). Type III is associated with more potential damage from iatrogenic injury.50

Variations Related to Sphenoid Sinus Four types of optic nerve canals (OCs) have been described, depending upon the relationship of the OC with the posterior sinuses.12 Type I OC is the commonest type and runs immediately adjacent to the sphenoid sinus, without indentation of the wall or contact with the posterior ethmoid air cell. Type II OC courses like the type I but indents the sphenoid sinus wall. Type III OC runs through the sphenoid sinus, with at least 50% of the nerve being surrounded by air, and type IV OC lies immediately adjacent to the sphenoid sinus and the posterior ethmoid air cells (see Fig. 23-5). Anterior clinoid process pneumatization is associated with type II and type III OCs and predisposes the optic nerve to injury during FESS.12,35,60 The carotid artery canal may form a bulge into the sphenoid sinus wall. Sometimes the sinus wall separating the optic nerve or the carotid artery from the sinus may be dehiscent, or the intersphenoid sinus septum may be attached to the sinus wall covering them, and thus arterial or nerve injury may occur when the septum is avulsed during surgery (see Fig. 23-5A).

Sinusitis means inlammation of the sinus mucosa. Several forms are described based on the duration of symptoms. Acute sinusitis is almost always sudden in onset and may last up to 4 weeks. Subacute sinusitis is a continuation of the acute process and lasts anywhere between 4 and 12 weeks. Chronic sinusitis is deined as sinonasal inlammation that lasts for 12 weeks and beyond. The disease is termed recurrent acute sinusitis when there are more than four episodes of acute sinusitis. Acute sinusitis is most commonly an inlammatory response to an upper respiratory viral infection that causes sinonasal mucosal congestion and edema that may lead to sinus obstruction and bacterial proliferation. Chronic sinusitis develops secondary to acute disease that is refractory to treatment and is generally a sequelae to the interference of the normal mucociliary drainage of the paranasal sinuses. Imaging is neither routinely recommended nor performed for every patient who presents with sinusitis. The American Academy of Otolaryngology, in its 2007 clinical practice guidelines, recommended against diagnostic imaging for patients with acute or subacute sinusitis unless an intraorbital or intracranial complication is suspected. Imaging is recommended in patients who fail to respond to medical treatment, present with recurrent sinusitis, or have unilateral recurrent symptoms when an alternate diagnosis of neoplasia or fungal infection is suspected.41,47,53 CT is clearly superior to MRI for delineation of the bony anatomy and anatomic variants. CT shows the presence and extent of the sinonasal disease, nature of the sinonasal secretions, and presence of any intrasinus calciications. Hence CT is the preferred technique in preoperative evaluation of the paranasal sinuses and the accepted gold standard for delineation of inlammatory sinus disease due to obstruction. Coronal CT images almost simulate the appearance of the sinonasal cavities at endoscopy and are most preferred by endoscopic surgeons. Contrast CT or MRI have a role to play when there is suspicion of an intraorbital or intracranial extension of the disease.62,74

Imaging Findings Acute Sinusitis. CT and MRI may show nonspeciic mucosal thickening, submucosal edema, air-luid levels, or sinus secretions interspersed with air bubbles (Fig. 23-8). Acute sinonasal secretions are of a mucoid nature (−10 to 25 HU) and are typically hypointense on T1 and hyperintense on T2 sequences. An isolated air-luid level as the only inding in the sinus is fairly characteristic for acute sinusitis but may not be seen in all patients.62 Complications of acute sinusitis include orbital cellulitis, orbital abscess, empyema, meningitis, brain abscess, and superior ophthalmic vein and/or cavernous sinus thrombosis. Although they can be visualized on contrast CT, intracranial complications and assessment of the orbital apex are best done on contrast MRI studies.

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FIG 23-8 Axial CT image shows a luid level in the left maxillary sinus (arrow) with presence of air bubbles. Acute left maxillary sinusitis.

FIG 23-10 Axial CT section in soft tissue algorithm shows complete opaciication of the right maxillary sinus with sclerosis of the walls of the sinus. The sinus disease shows a thin rim of hypodensity bordering the mildly hyperdense inner contents. Chronic right maxillary sinusitis.

both the T1 and T2 signal intensity, mimicking a signal void.62,63,76 In such cases, sinus disease may be completely missed on MRI, while CT may show the sinus illed with chronic desiccated secretions. Other features of chronic sinusitis include retention cysts, polyps, and mucoceles.

Retention Cyst. Two forms of retention cysts have been described:

FIG 23-9 Axial CT image shows sclerosis of the walls of the right maxillary sinus (white arrows) with presence of mucosal thickening (arrowheads). Chronic right maxillary sinusitis.

serous and mucous retention cysts. They are very common incidental indings. Serous cysts are due to accumulation of serous luid in the submucosal layer of the sinus mucosa, whereas mucous forms result from obstruction of a submucous mucinous gland. They are most commonly found in the maxillary sinuses and cannot be differentiated from one another. They are both seen as mucoid low-density welldeined lesions on CT and low signal on T1-weighted and high signal on T2-weighted MRI sequences.

Polyp. Polyps are the commonest expansile masses in the sinuses

Chronic Sinusitis Imaging features include nonspeciic mucosal thickening, sinus opaciication, intrasinus calciications, and sclerosis (reactive osteitis) of the bony walls of the sinus (Figs. 23-9 and 23-10). Mucosal thickening is common to both acute and chronic forms of sinusitis. Presence of a sclerotic thickened bone is a fairly characteristic feature of chronic sinusitis but may not be seen in all patients.62 Calciications are generally more peripheral and scattered.73 Air-luid levels may be seen. Whereas secretions in acute sinusitis are watery, chronic secretions vary in their luid and protein content, thereby affecting their CT and MR appearances. With chronicity, secretions lose water and become more proteinaceous and hence appear denser on CT. A thin hypodense line is usually seen separating the dense sinus secretions from the bony wall and represents thickened mucosa and submucosal edema (see Fig. 23-10).62,75 Progressive increase in the protein content of the secretions from 5% to about 25% results in an increase in the T1-weighted signal from low to high intensity. With increase in protein content beyond 25% to about 35%, the T2 signal begins to drop (Fig. 23-11). A very high protein content beyond 35% causes loss of almost all water from the secretions and results in a fall of

and may be solitary or multiple (Fig. 23-12). They are generally small but may grow and become very deforming. They result from accumulation of luid in the deeper lamina propria of the sinus mucosa. Allergic polyps are generally multiple and occur most commonly in the ethmoid air cells. An antrochoanal polyp is usually unilateral, solitary, and seen in young adults. It is a large polyp in the maxillary sinus that expands and ills the antrum and prolapses through the primary or accessory ostium into the nasal cavity. The ostium and the infundibulum are widened. The polyp ills the nasal cavity and extends behind into the nasopharynx (see Fig. 23-12). Polyps and cysts cannot be differentiated on CT or MRI; however, it is of little consequence because they are both treated in the same manner. When multiple polyps are present, they may show varying densities on CT and have variable T1 and T2 signals due to the differing nature of secretions; this helps distinguish them from masses that have more homogeneous signals.

Mucocele. Mucocele is the commonest expansile lesion of the paranasal sinuses, most commonly seen in the frontoethmoid sinuses. It develops as a result of obstruction of a sinus ostium or a compartment of a septate sinus and hence is lined by the sinus mucosa. CT shows

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B FIG 23-11 A, Axial T1-weighted image with mild hyperintensity of the contents of the left maxillary sinus (IS). B, Corresponding T2-weighted image shows intrasinus hypointensity due to inspissated secretions (IS). Note the hyperintense mucosal thickening surrounding the inspissated secretions. Thin rim of mucosal disease is also seen in the right maxillary sinus.

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FIG 23-12 Coronal CT (A) and axial CT (B) images show an antrochoanal polyp on the right side. Note the polyp prolapsing out of the sinus through the accessory ostium (arrow). A maxillary sinus polyp/retention cyst is seen in the left maxillary sinus (arrowhead).

an expanded airless sinus cavity with bony remodeling of the sinus walls, illed with fairly homogenous mucoid attenuation62,63 (Fig. 23-13). If the secretions are thick and proteinaceous, attenuation can increase to 25 to 40 HU. MRI typically shows low T1 and high T2 signals. If the secretions become proteinaceous, the T2 signal drops, with mild increase in T1 signals.

Patterns of Inlammatory Sinonasal Disease Sinonasal inlammatory disease has been categorized into ive patterns for better understanding and interpretation and importantly to group the patients into nonsurgical (normal CT), routine surgical (I and II), and complex surgical groups (III and IV). Groups I to III are obstructive patterns and based on the major routes of mucociliary drainage that have been previously described.66 I. Infundibular pattern: obstruction is at the maxillary ostium and infundibulum and causes disease limited to the maxillary sinus (see Fig. 23-1). The remainder of the anterior OMU is patent, and therefore the anterior ethmoid and frontal sinuses are normal. Because the frontal sinus and anterior ethmoids may also drain

FIG 23-13 Axial CT image shows a mucocele arising from the left anterior ethmoid air cells (curved arrow).

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SO SO SO C

A

B FIG 23-14 A, Coronal CT image depicting left-sided osteomeatal pattern of sinonasal inlammatory disease. Opaciication of the middle meatus, frontal recess, ethmoid infundibulum, anterior ethmoid air cells, and supraorbital ethmoid air cell (SO) on the left side is noted. Lamellar concha (C) is seen on the right side. The supraorbital ethmoid air cell (SO) is seen posterior and lateral to the frontal sinus, better appreciated in axial CT image (B) at the level of the frontal sinuses (FS). Note mucosal disease in left frontal sinus and the supraorbital cell on this image.

II.

III.

IV.

V.

into the infundibulum, the obstruction is presumed to be in the posteroinferior aspect of the infundibulum. OMU pattern: obstruction is at the level of the middle meatus, leading to inlammatory sinonasal disease within the ipsilateral maxillary, frontal, and anterior and middle ethmoid sinuses (Fig. 23-14). There may be variable amounts of disease in the affected sinuses owing to slight variations in the placement of the draining ostia. This has been speciically noted for the frontal recess that drains the frontal sinus, and hence the frontal sinus may be spared in the OMU pattern of disease. Similarly, isolated frontal sinus disease may also occur when the obstruction is limited to the anterior aspect of the middle meatus. Sphenoethmoid recess pattern: obstruction is at sphenoethmoid recess, causing inlammatory disease limited to the sphenoid sinus and posterior ethmoid air cells. Isolated sphenoid disease without posterior ethmoid sinus disease can be seen in the SER pattern because the sphenoid sinus drains directly into the SER and the posterior ethmoid initially drains more anteriorly into the superior meatus. Sinonasal polyposis: characterized by polyps diffusely present within the nasal cavity and paranasal sinuses, illing the nasal vault and sinuses, causing bilateral infundibular enlargement, convex (bulging) ethmoid sinus walls, and attenuation of the bony nasal septum and ethmoid trabeculae (Fig. 23-15). Truncation of the bulbous portion of the middle turbinates may be seen.39 Isolated polyps are not included in this disease pattern. It is often associated with allergic fungal sinusitis. Sporadic pattern: diagnosed when inlammatory sinonasal disease is not attributable to obstruction of known mucous drainage routes or polyposis and there is randomly placed disease noted anywhere within the sinuses. This group includes individual inlammatory lesions such as retention cysts and mucoceles.

FUNGAL SINUSITIS Fungal infections of the paranasal sinuses are not uncommon, and there has been an increase in their incidence across the world over

FIG 23-15 Coronal CT image shows diffuse opaciication of the sinonasal cavities with widening of the osteomeatal units and deossiication of the ethmoid trabeculae. Sinonasal polyposis.

the last decade. They are associated with high morbidity, and certain forms of these infections can be fatal. Although CT and MRI offer important diagnostic clues and depict certain characteristic features in most forms of these infections, the right diagnosis may still be elusive in some cases. A sound knowledge of the radiologic features, however, enables the radiologist to alert the surgeon about the diagnosis, prompting adequate sampling for fungal stains, cultures, and histopathologic examination. Etiologic fungi in most cases belong to the Aspergillus genus or the Phycomycetes group.9,20 Fungal sinusitis is broadly divided into invasive and noninvasive forms. The diagnosis of invasive fungal sinusitis is made when there is (a) invasion of the mucosa, submucosa, or blood vessels by the fungal hyphae or (b) tissue necrosis with minimal host inlammatory cell iniltration.20 Although the noninvasive forms occur almost exclusively in immunocompetent patients, they may progress to invasive forms if the immunologic status

CHAPTER 23

A

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693

B FIG 23-16 A, Axial CT section in a patient following renal transplant shows left maxillary sinus disease. Mild edema in the left retroantral fat (arrows) and a thin rim of retroantral soft tissue (arrowhead) are seen. B, Bone window shows subtle focal irregularity of the posterolateral wall of the left maxillary sinus. Fungal culture showed Aspergillus. Early acute invasive fungal sinusitis.

of the patient changes. These forms are further divided into ive major subtypes based on their natural history and clinical and radiologic features.9

Invasive Fungal Sinusitis Acute Invasive Fungal Sinusitis. Acute invasive fungal sinusitis (AIFS) is the most dangerous and rapidly progressive form of fungal sinusitis, seen almost exclusively in individuals with poorly controlled diabetes mellitus or in immunosuppressed patients. The primary sites of infection are the nasal cavity and the middle turbinate, and a distinct predilection for unilateral involvement of the sphenoethmoid sinuses is noted.21,22 The fungi have a propensity to spread through the perivascular channels and hence cross the bony sinus walls through the penetrating vessels to reach the periantral soft tissues of the maxillofacial region, the orbit, and the cranial cavity. Early features of the disease on noncontrast CT include hypodense mucosal thickening and intranasal or intrasinus soft tissue, with bony erosion. The mucosal thickening is hypointense on T1-weighted and hyperintense on T2-weighted images. These indings may be subtle, and it can be very dificult to differentiate early AIFS from other nonspeciic sinusitis at imaging. Presence of unilateral nasal cavity soft tissue thickening is the most consistent, though nonspeciic, early CT inding.2,22 Early extrasinus spread is seen as obliteration or edema of the normal fat density in the periantral fat and within the orbit across normal-appearing sinus walls (Fig. 23-16). Deep spread into the periantral soft tissues, with destruction of sinus walls and intraorbital and intracranial extension are late, though fairly speciic, indings in AIFS.13,37,43 Bone changes are best appreciated on CT, but intraorbital and intracranial extension are best delineated on contrast MRI. As the intraorbital disease spreads, there may be thickened extraocular muscles, thrombosis of the superior ophthalmic vein, and even cavernous sinus thrombosis. Features of intracranial extension include leptomeningeal enhancement, granulomas, cerebritis, cerebral abscess formation, carotid artery invasion, pseudoaneurysm formation, and intracerebral infarct and hemorrhage.2,19,37,62

Chronic Invasive Fungal Sinusitis. CIFS is a slowly progressive form of fungal infection that develops over months to years and

is also associated with high morbidity. It is commonly seen in immunocompetent patients, but immunocompromised patients and those with diabetes mellitus may also be affected. Patients generally present with history of chronic sinusitis. Noncontrast CT shows a mildly hyperdense soft tissue mass in the paranasal sinus, sinus wall erosion, and extension of the mass beyond the walls of the sinus.2,13,19,37,43,59,68 On MRI, the soft tissue is iso- to hypointense on T1 images and markedly hypointense on T2 sequences (Fig. 23-17). Invasion of the adjacent periantral region, the orbit, and anterior cranial fossa that are seen with AIFS may also be seen with the chronic form and are best appreciated on MRI. The differential diagnoses for intrasinus hyperdensity at CT include chronic inspissated secretions, fungal infection, intrasinus hemorrhage, and calciications.62,63 Although the diagnosis of intrasinus hemorrhage is most often facilitated by the history and possible associated fractures, it may be almost impossible to differentiate chronic inspissated inlammatory sinus disease from fungal disease in the absence of bone erosion at imaging. Presence of mottled irregular bone erosion is perhaps the only sign that favors the diagnosis of an aggressive fungal infection over chronic inspissated secretions.18 Although intrasinus hyperdensity at CT almost completely excludes the diagnosis of a sinonasal malignancy, at times the differentiation of CIFS from sinonasal malignancy may be dificult.63 At such times, the markedly hypointense signal of CIFS on T2-weighted images is a differentiating feature from a sinonasal malignant neoplastic mass, which shows an intermediate signal on T2 images63 (Fig. 23-18).

Chronic Invasive Granulomatous Sinusitis. This is a rare condition, very similar clinically and radiologically to CIFS and occurring almost exclusively in immunocompetent patients from North Africa and South America.9,20

Noninvasive Fungal Sinusitis Allergic Fungal Sinusitis. Allergic fungal sinusitis (AFS) is the commonest form of fungal sinusitis. Unlike the other forms, it is not an infection but postulated to be a hypersensitivity reaction to inhaled fungal organisms, resulting in a chronic inlammatory disease process. It is commonly seen in warm humid climates and affects younger immunocompetent individuals.9,20,58 Patients

694

PART II CT and MR Imaging of the Whole Body

A

B FIG 23-17 A, Axial CT section in a patient with chronic rhinosinusitis with symptoms of right-sided orbital apex syndrome shows patchy opaciication of the right sphenoethmoid sinuses with erosion of the right lamina papyracea and lateral wall of the right sphenoid sinus. Abnormal soft tissue is seen in the region of the right orbit, orbital apex, and cavernous sinus. B, T2-weighted MRI section at the same level. Mucosal disease is seen in the right sphenoethmoid sinus. Note the hypointense soft tissue in the right orbit, orbital apex, and right cavernous sinus (arrowheads). Note also hypointense soft tissue in right anterior ethmoid air cells (curved arrow). Chronic invasive fungal sinusitis.

E

IS IS

A

B FIG 23-18 A, Coronal CT reformatted section shows hyperdense soft tissue in the nasoethmoid region, with erosion of the anterior skull base and fairly large intracranial extension (arrowheads) and edema in the bifrontal lobes (E). Intrasinus hyperdensity is also seen in the left maxillary sinus. B, Coronal T2-weighted MRI shows the soft tissue with profoundly hypointense signal (arrowheads) and mild edema in the bifrontal lobes. Hypointense signal in left maxillary sinus is due to chronic inspissated secretions (IS); this shows a hyperintense signal on T1-weighted images not shown here.

CHAPTER 23

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B

A

FIG 23-19 A, Axial CT image shows bilateral polypoid expansile disease with marked hyperdensity in the ethmoid sinuses bilaterally and left sphenoid sinus. Note erosion of the lamina papyracea with intraorbital extension of the disease. B, Disease in the maxillary sinuses. Note erosion of the posterolateral wall of left maxillary sinus. Allergic fungal sinusitis.

generally have a history of atopy, chronic sinusitis, and polyposis.14,49 The diagnosis of AFS may often be irst suggested at CT, and the radiologist plays a crucial role in alerting the physician to the possibility of this entity. Presence of allergic mucin at endoscopy is characteristic of the disease. The disease may be unilateral or bilateral but asymmetric and shows near-complete opaciication of multiple sinuses with polypoid masses (Fig. 23-19). Presence of allergic mucin produces the characteristic intrasinus hyperdensity in a background of hypodense polypoid mucosal disease, giving rise to the “double-density sign.”37,43,49 This hyperdensity is best appreciated on soft tissue algorithm images and is due to the combination of heavy metals (iron and manganese), calcium, high protein, and low water content of the allergic mucin.56 There may be sinus expansion encroaching onto the adjacent orbits and erosion of the walls, with associated extrasinus extension into the orbit and the cranial cavity (see Fig. 23-19). Presence of sinus expansion with thinning of the walls instead of reactive sclerosis differentiates AFS from chronic sinusitis with desiccated secretions.49,56 Whereas T1 intensity of allergic fungal sinusitis is variable, the T2 signal is very low owing to metals concentrated by the fungal organisms, high protein, and low water content of the mucin and may lead to underdiagnosis; hence CT is best suited for the diagnosis. Contrast study shows enhancement of the peripheral mucosa with central areas of nonenhancement.

Fungus Ball (Mycetoma). This relatively uncommon type of fungal sinusitis is a dense extramucosal conglomeration of fungal hyphae without any allergic mucin, found in immunocompetent patients in older age groups. It generally occurs in a single sinus cavity, the commonest sinus being the maxillary sinus, followed by the sphenoid sinus.2,19,37 Noncontrast CT shows a hyperdense mass due to the dense matted fungal hyphae within the involved sinus, with occasional intrasinus calciications (Fig. 23-20). Most of these calciications occur centrally within the sinus.73 Surrounding hypodensity due to mucosal thickening is usually present, and there may be reactive osteitis due to chronic sinusitis. No bony erosion is seen. The fungus ball is hypointense on T1- and T2-weighted images owing to the absence of free water, calciications, and paramagnetic metals such as iron, magnesium, and manganese.

FIG 23-20 Axial CT image shows thickened walls of the right maxillary sinus with intrasinus central hyperdensity and calciications. Mycetoma was found at histopathology.

GRANULOMATOUS DISEASES OF THE SINONASAL CAVITIES Granulomatous diseases can be of an infective or noninfective nature. Infectious causes of granulomatoses include actinomycosis, tuberculosis, leprosy, and syphilis. Wegener’s granulomatosis and sarcoidosis are noninfectious granulomatous processes. Wegener’s granulomatosis is a systemic vasculitis that can affect any organ system but primarily involves the upper and lower respiratory tracts and kidneys. Imaging indings in Wegener’s granulomatosis can be broadly divided into mucosal and bony changes. Mucosal lesions range from nonspeciic mucosal thickening and sinus opaciication to granuloma formation that are low signal on T1 and intermediate to high signal on T2-weighted sequences.48 Bony changes include erosion, mainly involving the septum, turbinates, and the medial wall of the maxillary sinuses, followed by sclerosing osteitis of the sinus wall. The combination of bone erosion, remodeling, and sclerosis gives rise to

696

PART II CT and MR Imaging of the Whole Body Classiication of Paranasal Sinus Neoplasms25 BOX 23-1

Epithelial Tumors • Papilloma • Squamous cell carcinoma • Adenocarcinoma • Adenoid cystic carcinoma • Metastases

FIG 23-21 Coronal CT image shows reduced caliber of the sinus, mildly thickened sinus walls, opaciication of the sinus and the ethmoid infundibulum (arrow), with inward retraction of the walls of the right maxillary sinus (arrowheads). Note the increase in right orbital volume. Silent sinus syndrome.

the tramline effect in the antrum and may eventually lead to complete bony obliteration of these sinuses.40,72 Although these indings are suggestive of Wegener’s granulomatosis, they are not pathognomonic of the disease and should be combined with clinical and laboratory studies to conirm the diagnosis.

Nonepithelial Tumors Neuroectodermal and Nervous System Tumors • Malignant melanoma • Nasal glioma • Olfactory neuroblastoma • Neuroendocrine tumor • Peripheral nerve sheath tumor • Ewing’s sarcoma and PNET • Meningioma Mesenchymal Tumors • Juvenile nasopharyngeal angioibroma • Angiomatous polyp • Hemangioma • Hemangiopericytoma Osseous and Cartilaginous Tumors • Osteosarcoma • Chondrosarcoma • Soft tissue sarcoma • Rhabdomyosarcoma

SILENT SINUS SYNDROME This is a unilateral atelectasis of the maxillary sinus, with partial or complete opaciication of the sinus; it is seen in adults. Patients generally present with progressive enophthalmos and facial asymmetry. Although most cases are idiopathic, trauma to the lateral nasal wall may be the cause in some patients. The primary imaging inding is reduced caliber of a fully formed maxillary sinus due to inward retraction of the sinus walls, occlusion of the maxillary ostium and infundibulum, and sinus opaciication and reactive osteitis of the sinus walls due to chronic inlammation (Fig. 23-21).28,31 The orbital loor is almost always retracted and a resultant increase in the orbital volume is noted. Chronic occlusion of the maxillary sinus ostium results in gradual resorption of the air, with subsequent generation of negative pressure that causes gradual inward bowing of the sinus wall.

TUMORS OF THE PARANASAL SINUSES Sinonasal tumors are rare neoplasms and account for less than 3% of head and neck cancers. A variety of sinonasal tumors have been described and have an overall poor prognosis. There are differences in the age at presentation of the affected patients; sinonasal carcinomas are generally seen in the elderly population, but some tumors like lymphomas, olfactory neuroblastomas, and minor salivary gland tumors also present in younger patients.3 The sinonasal tumors are broadly classiied into epithelial and nonepithelial types (Box 23-1). Patients with sinonasal masses often present late and with nonspeciic symptoms that may be attributed to those of chronic sinusitis. Hence a plain CT scan is generally the irst test performed on these patients. Features at CT that should alert the radiologist to

Lymphoreticular Tumors • Lymphoma • Plasmacytoma Fibroosseous Tumors • Fibrous dysplasia • Ossifying ibroma • Cementifying ibroma • Cemento-ossifying ibroma • Osteoma PNET, primitive neuroectodermal tumor.

the presence of a possible neoplastic mass lesion include persistent unilateral sinus opaciication, extrasinus disease, bony remodeling, and bone destruction. Whereas benign masses expand the sinus cavity and may cause bone remodeling and pressure erosion, local bone destruction is characteristic of malignant tumors (see Figs. 23-23D and Fig. 23-24).61 Benign processes generally have a smooth polypoid margin, and even when they extend intracranially, they usually retain this contoured appearance. Malignant masses, however, frequently show irregular and nodular margins.10 Erosion of the nasoethmoid roof, posterolateral wall of the maxillary sinus, or the lamina papyracea are all very well appreciated on CT.16,25 Often contrast MDCT optimally shows the tumor extension, with changes of bony remodeling or destruction and presence of intratumoral calciications; it also delineates the tumor from the nonenhancing sinonasal secretions. MRI delineates the soft tissue extent and early extrasinus spread into the orbit, skull base, nasopharynx, and intracranial cavity with

CHAPTER 23

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697

of the tumor alongs the second division of the ifth cranial nerve, better depicted at MRI than at CT. Spread into the dura and brain parenchyma is better seen on a contrast MRI. Linear dural enhancement is not speciic for dural invasion and is generally due to reactive changes. Signs of dural involvement by malignant tumors include focal nodularity, dural thickening of more than 5 mm, and pial enhancement.17 There may also be edema in the adjacent brain parenchyma (see Fig. 23-25). Brain invasion is seen as enhancement of the brain parenchyma.

Papilloma

FIG 23-22 Coronal T2-weighted MRI section shows a mass lesion centered in the middle meatus, lateral nasal wall, and maxillary antrum, with a convoluted cerebriform pattern. Note superb delineation of the mass from the surrounding sinonasal secretions. Inverting papilloma.

greater precision than contrast CT. MRI is also preferred over CT to detect perineural spread. Another major advantage of MRI is better differentiation of tumor from the coexistent inlammatory sinonasal disease. Malignant masses are highly cellular and have very little free water, and hence they show an intermediate signal on T2-weighted MR scans (see Fig. 23-23B).10,61 The more benign and glandular-type tumors such as papillomas and minor salivary gland tumors usually have suficient water to produce hyperintensity on T2-weighted MRIs (Fig. 23-22).42,63 It is important to note that although the T2 signal of the mass is intermediate, it is still higher than the T1 signal, known as tumor brightening on T2-weighted scans (Fig. 23-23A and B).10,63,61 A T2 signal in a mass that is lower than the T1 signal almost excludes a sinonasal tumor.63 The intermediate T2 signal intensity also allows separation of the tumor mass from high-intensity inlammatory changes (see Fig. 23-23B). Speciic histologic diagnosis is not possible using MRI, because the observed signal intensities in different tumors show substantial overlap.75 The neck nodes are not routinely assessed on MRI of the sinuses, but when spread to the pharynx or oral cavity is seen, the deep cervical nodes should be evaluated. The presence of metastatic lymph nodes signiies poor prognosis.70 The primary role of imaging in sinonasal neoplasia is to delineate the exact extent of the tumor, and CT and MRI often complement each other in most aspects. Sinonasal malignancies often show spread into the adjoining orbit, skull base, cranial cavity, pterygopalatine fossa, and the masticator space. Spread into the anterior skull base and intracranial cavity is common in patients with nasoethmoid cancers. Invasion of the infratemporal fossa, pterygopalatine fossa, and the masticator space are commonly seen with maxillary sinus cancers (see Fig. 23-23). Orbital invasion may occur with both maxillary and ethmoid tumors. The pterygopalatine fossa may get involved also by perineural spread

Papillomas are uncommon sinonasal masses. Three histologic varieties of papillomas are described: fungiform, inverted, and oncocytic, collectively called schneiderian papillomas.69 Fungiform (or exophytic) papillomas arise from the nasal septum and are solitary and unilateral. These have a verrucous appearance and are not considered premalignant. Inverted (or endophytic) papillomas arise from the lateral nasal wall in the region of the middle turbinate and extend into the sinuses. The tumor shows a fairly strong male predilection. Although this is a benign tumor, it may behave aggressively, may commonly show recurrence after resection, and in 7% to 15% of patients squamous cell carcinoma (SCC) may coexist with the tumor.30,51 It derives its name from the characteristic invagination of the epithelium seen on histopathology. The anatomic location and its extent may be seen fairly well on CT. Sclerosis of the sinus wall may be seen at times. MRI features may be nonspeciic in smaller masses, but larger masses show a convoluted “cerebriform” pattern on T2-weighted and contrastenhanced T1-weighted images (see Fig. 23-22). This pattern consists of low-signal-intensity and relatively high-signal-intensity striations on T2-weighted images that probably represent metaplastic squamous epithelium and edematous stroma, respectively.32,55,74 Contrastenhanced T1-weighted images show well-enhancing stroma and less-enhancing epithelium that create a convoluted cerebriform pattern. Oncocytic (or cylindrical) papillomas have imaging features similar to the inverted papilloma variety.

Carcinoma SCC is the commonest malignant tumor of the sinonasal cavity, constituting about 60% of sinonasal tumors, followed by adenocarcinoma and adenoid cystic carcinoma. An increased risk of developing adenocarcinoma has been seen in woodworkers.3 Although the maxillary sinus is the commonest site for occurrence of SCC, adenocarcinomas are seen more commonly in the ethmoid sinuses and the superior part of the nasal cavity. There are no speciic features, and MRI shows an intermediate-signal-intensity mass on T1 and T2 sequences, with bone destruction. Adenoid cystic carcinoma (ACC) is the commonest minor salivary gland tumor seen in the sinonasal cavities, most commonly found in the maxillary sinus, followed by the nasal cavity. However, more commonly ACC arises in the palate and secondarily involves the sinonasal cavities. Unlike SCC, ACC is a slow-growing neoplasm. It is a locally aggressive tumor with a high propensity for local recurrence, perineural spread, and distant metastases.23

Malignant Melanoma These rare tumors arise from the melanocyte precursors present in the sinonasal mucosa. They have a poor prognosis, a high rate of recurrence, and also a high incidence of distal metastases. Most arise in the nasal cavity, followed by the maxillary sinus.11 Imaging shows a fairly well-deined polypoid nasal or intrasinus mass. Bone remodeling is generally more common than bone destruction. A characteristic T1 hyperintensity due to melanin or hemorrhage is seen with an intermediate signal on T2-weighted MR scans.

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PART II CT and MR Imaging of the Whole Body

B

A

D

C FIG 23-23 Axial T1 (A) and T2 (B) sections show a large left maxillary sinus mass with extension into the periantral soft tissues (arrowheads). Posteriorly the mass extends into the retroantral fat and left masticator space (curved white arrow). Note the intermediate signal of the mass on T2-weighted images. Note the normal retroantral fat (double-headed white arrow) and masticator space (dotted white lines) posterior to the right maxillary sinus; the pterygoid plates are better seen medially on axial CT. C, Contrast-enhanced T1-weighted MRI with fat suppression shows mild extension of the mass into the loor of the left orbit. D, Axial CT shows signiicant destruction of the walls of the left maxillary sinus (black arrows). Squamous cell carcinoma of the left maxillary sinus. Chronic right-sided maxillary sinusitis is seen.

Schwannoma

Olfactory Neuroblastoma

This is an infrequent tumor of the sinonasal cavity that arises from the irst or second division of the ifth cranial nerve. On contrast CT, the lesion is seen as a moderately enhancing fairly well-deined mass that frequently remodels the bone as it grows (Fig. 23-24). On MRI the mass is hyperintense on T2 images owing to a fairly good amount of free water within it. Necrosis and cystic changes may lead to an inhomogeneous appearance.15 Presence of aggressive bone destruction may be considered an indication of malignant transformation.

This is a rare tumor of neuroectodermal origin that arises from the olfactory epithelium in the roof of the ethmoidal sinuses, in the cribriform region, upper part of the nasal septum, and superior turbinates, generally seen in adults between 20 and 40 years of age. Imaging shows an enhancing soft tissue mass, with or without bone destruction, centered in the nasal vault, with or without extension into the ethmoid sinuses, orbit, and cranial cavity, depending on the stage of the disease. Calciication may be seen on CT. Intracranial extension is

CHAPTER 23

FIG 23-24 Contrast-enhanced axial CT image shows a mildly enhancing expansile mass in the right nasal cavity causing remodeling of the walls of the nasal cavity. Intranasal schwannoma. Chronic right maxillary sinusitis with inspissated secretions is noted.

Paranasal Sinuses

699

FIG 23-26 Axial contrast CT image in a 12-year-old boy with epistaxis shows moderately enhancing mass centered in the left sphenopalatine foramen, extending into the nasal cavity, nasopharynx, pterygopalatine fossa, retromaxillary region, and masticator space, eroding the pterygoid plates and posterolateral wall of the left maxillary sinus with intrasinus extension. Juvenile nasopharyngeal angioibroma. Note mucosal disease in right maxillary sinus.

E paranasal sinuses. Stage C includes tumors with orbital, skull base, or intracranial spread and distant metastases.

Juvenile Nasopharyngeal Angioibroma Juvenile nasopharyngeal angioibroma is a benign but locally aggressive tumor with a very rich vascular supply from the internal maxillary artery and the ascending pharyngeal artery. It occurs almost exclusively in male adolescents, and patients generally present with epistaxis. The site of origin is the sphenopalatine foramen and pterygopalatine fossa, and the sinonasal space is involved secondarily. They frequently grow to very large sizes and spread into adjacent regions along the skull base and superiorly into the cranial cavity. In the early stages, there may be anterior bowing of the posterior wall of the maxillary sinus and widening of the pterygopalatine fossa; frank bone destruction may be seen as the tumor grows. Contrast CT shows an intensely enhancing mass with bone destruction in the characteristic location and the characteristic age group (Fig. 23-26). The arterial phase of contrast injection shows the hypervascular nature of the mass. On MRI, heterogeneous signals are seen on T1- and T2-weighted scans, with presence of low voids. Intense enhancement is seen following administration of contrast. FIG 23-25 Coronal T1 contrast MRI shows an enhancing mass centered in the superior nasal cavity, eroding the anterior skull base and extending into the cranial cavity. Note the cysts at the growing margin of the mass lesion (arrowhead). Mild edema of the bifrontal lobes is seen (E). Note mucosal disease in both the maxillary sinuses.

often dumbbell shaped, the narrow part being in the region of the cribriform plate. Cysts are often present at the interface between the brain and tumor64 (Fig. 23-25). These tumors are clinically staged using the Kadish staging system.33 Stage A includes tumors limited to the nasal cavity, stage B includes tumors limited to the nasal cavity and

Lymphoma Paranasal sinuses are an uncommon extranodal site for lymphomas. There are usually two types of lymphomas that involve the paranasal sinuses, the B-cell type and the T-cell type. The T-cell type is more prevalent in Asian and South American populations. The T-cell type usually occurs in the nasal cavity and can be very aggressive, with destructive changes.15 Many of the sinonasal lymphomas are EpsteinBarr virus associated. The destructive “lethal midline granuloma” described in the literature has been proven to be the T-cell variety of lymphoma involving the sinonasal region. B-cell lymphomas occur in the sinuses and are indolent in their behavior. They are more common in Western populations. The lesions appear as bulky soft tissue masses. There is bone remodeling, with the maxillary sinus being commonly

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PART II CT and MR Imaging of the Whole Body

FIG 23-27 Coronal CT image shows smooth expansion with ground-

FIG 23-28 Axial CT shows fracture of the pterygoid plates bilaterally,

glass appearance of the walls of the ethmoid labyrinth on the right side and the right middle turbinate. Fibrous dysplasia.

posterolateral wall of both maxillary sinuses, anterior wall of right maxillary sinus, and the right zygomatic arch.

involved by B-cell disease.26 On MRI, the lesions are of intermediate signal and show mild enhancement. Unlike carcinomas, these lesions do not show invasion toward the skull base.

keratocyst is seen as a multiloculated cystic mass with scalloped borders that may bulge into the maxillary sinus. Most odontogenic tumors are common in the mandible but may occur in the maxilla. Ameloblastoma is a benign epithelial odontogenic tumor that may be seen in the maxilla. It is a well-deined unilocular or multilocular expansile cystic lesion with interspersed isodense solid areas that causes moderate expansion, thinning, and often destruction of the maxilla. It may be dificult to differentiate an ameloblastoma from an odontogenic keratocyst.

Fibroosseous Lesions Fibroosseous lesions are probably the most common noninlammatory benign masses of the sinonasal region. This group comprises masses wherein the normal bone is replaced by benign ibrous tissue containing various amounts of mineralization/calciication.1,8,46 All of them are very well appreciated on CT. Fibrous dysplasia commonly affects the maxilla and mandible in the craniofacial region and is generally seen in children and adolescents. The medullary bone is expanded, with a hazy ground-glass density compared with the normal compact bone; the cortex is intact and the margins may be poorly deined1,8 (Fig. 23-27). Ossifying ibroma is an expansile mass lesion that is more commonly seen in the mandible, followed by the maxilla, in close proximity to the roots of the teeth. A juvenile form of the tumor is seen in adolescents, but the tumor is otherwise seen in young adults. CT shows a well-circumscribed expansile osteolytic lesion with homogenous ibrous matrix that may have a sclerotic border and a few discrete foci of osseous matrix. Osteoma is generally an incidental inding and is the commonest osseous tumor in the maxillofacial region. It is frequently seen in the frontoethmoid sinuses. It appears as a characteristic sharp, well-delineated sclerotic lesion attached by a broad base or pedicle to the bone. It produces a complete signal void on all MR sequences and may often be overlooked owing to the background of sinus air.

Odontogenic Cysts and Tumors Odontogenic cysts and tumors that arise from the maxillary alveolar ridge may extend into the maxillary sinus and present as sinus masses.71 All of them are very well delineated at CT. The odontogenic cysts of signiicance to the sinonasal region include the radicular cyst, dentigerous cyst, and odontogenic keratocyst. The radicular cyst is seen in relation to a carious tooth and appears as a well-deined cystic lesion bordered by a thin rim of cortical bone. Dentigerous cysts and odontogenic keratocysts are more common in the mandible. A dentigerous cyst is seen as a well-deined unilocular or multilocular cyst in relation to the crown of an unerupted tooth; the crown of the tooth projects into the cystic cavity. An odontogenic

Metastases The commonest cancer to metastasize to the paranasal sinuses is renal cell carcinoma, followed by lung and breast.38 Most metastases are to the bony walls.

MAXILLOFACIAL TRAUMA MDCT is the modality of choice for evaluation of maxillofacial trauma.52 For ease of understanding and interpretation, the facial anatomy is divided into upper, middle, and lower thirds. The upper third of the face consists of the frontal bone (including the frontal sinuses). The middle third of the face extends from the superior orbital rims inferiorly to the maxilla and thus includes the orbits, nasal cavity, and the maxillary, ethmoid, and sphenoid sinuses. The middle third of the face is bounded posterolaterally by the zygomaticotemporal sutures, which connect the midface to the calvaria, and posteromedially by the pterygoid plates, which connect it to the skull base. The lower third of the face consists of the mandible. Describing fractures by their location with regard to these facial thirds may be helpful for planning surgical access. Bony injury may involve the nasal bones or the bony walls of the paranasal sinuses, and various combinations may be noted (Fig. 23-28). In addition to the bony injury, it is important to comment on the presence of intrasinus hemorrhage and intrasinus displacement of fracture fragments. Assessment of the orbital walls, orbital apex, and optic nerve canal and the ethmoid and sphenoid roof for risk of cerebrospinal luid rhinorrhea and the visualized cranial cavity are of immense importance. Also of importance is the identiication of Le Fort fractures that are associated with disruption of the pterygoid plate (see Fig. 23-28). Because of the close proximity and associated

CHAPTER 23 disruption of the pterygoid venous plexus, it is important to recognize these fractures because of fairly high risk of large nasopharyngeal hematomas.

REFERENCES 1. Araghi HM, Haery C: Fibro-osseus lesions of cranio-facial bones: Role of imaging. Radiol Clin North Am 31:121–134, 1993. 2. Aribandi M, McCoy VA, Bazan C, III: Imaging features of invasive and noninvasive fungal sinusitis: A review. Radiographics 27:1283–1296, 2007. 3. Barnes L, Brandwein M, Som PM: Diseases of the nasal cavity, paranasal sinuses and nasopharynx. In Barnes L, editor: Surgical Pathology of the Head and Neck, ed 2, New York, 2003, Marcel Dekker, pp 509–517. 4. Beale TJ, Madani G, Morley SJ: Imaging of the paranasal sinuses and nasal cavity: Normal anatomy and clinically relevant anatomical variants. Semin Ultrasound CT MR 30:2–16, 2009. 5. Bolger WE: Anatomy of the paranasal sinuses. In Kennedy DW, Bolger WE, Zinreich J, editors: Diseases of the Sinuses, Diagnosis and Management, New York, 2001, Marcel Dekker. 6. Bruner E, Jacobs JB, Lebowitz RA: Role of the agger nasi cell in chronic frontal sinusitis. Ann Otol Rhinol Laryngol 105:694–700, 1996. 7. Caughey RJ, Jameson MJ, Gross CW, et al: Anatomic risk factors for sinus disease: Fact or iction? Am J Rhinol 19(4):334–339, 2005. 8. Celenk P, Zengin Z, Muglali M, et al: Computed tomography of cranio-facial ibrous dysplasia. Eur J Radiol Extra 69:e85–e87, 2009. 9. Chakrabarti A, Denning DW, Ferguson BJ, et al: Fungal rhinosinusitis: A categorisation and deinitional schema addressing current controversies. Laryngoscope 119:1809–1818, 2009. 10. Chow JM, Leonetti JP, Mafee MF: Epithelial tumors of the paranasal sinuses and nasal cavity. Radiol Clin North Am 31:61–73, 1993. 11. Conley JJ: Melanomas of the mucous membrane of the head and neck. Laryngoscope 99:1248–1254, 1989. 12. DeLano MC, Fun FY, Zinreich SJ: Optic nerve relationship to the posterior paranasal sinuses. CT Anatomic study. AJNR Am J Neuroradiol 17:669–675, 1996. 13. Delgaudio JM, Swain RE, Jr, Kingdom TT: CT indings in patients with invasive fungal sinusitis. Arch Otolaryngol Head Neck Surg 129:236–240, 2003. 14. DeShazo RD, Swain RE: Diagnostic criteria for allergic fungal sinusitis. J Allergy Clin Immunol 96(1):24–35, 1995. 15. Dublin AB, Dedo HH, Bridger WH: Intranasal schwannoma: Magnetic resonance and computed tomography appearance. Am J Otolaryngol 16:251–254, 1995. 16. Eisen MD, Yousem DM, Loevner LA, et al: Preoperative imaging to predict orbital invasion by tumor. Head Neck 22:456–462, 2000. 17. Eisen MD, Yousem DM, Montone KT, et al: Use of preoperative MR to predict dural, perineural, and venous sinus invasion of skull base tumors. AJNR Am J Neuroradiol 17:1937–1945, 1996. 18. Fatterpekar G, Delman BM, Som PM: Imaging the paranasal sinuses– Where are we and where we are going. Anat Rec (Hoboken) 291:1564– 1572, 2008. 19. Fatterpekar G, Mukherji S, Arbealez A, et al: Fungal diseases of the paranasal sinuses. Semin Ultrasound CT MR 20:391–401, 1999. 20. Ferguson BJ: Deinition of fungal rhinosinusitis. Otolaryngol Clin North Am 33(2):389–398, 2000. 21. Gillespie MB, Huchton DM, O’Malley BW: Role of middle turbinate biopsy in the diagnosis of fulminant invasive fungal rhinosinusitis. Laryngoscope 110:1832–1836, 2000. 22. Gillespie MB, O’Malley BW, Jr, Francis HW: An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg 124(5):520–526, 1998. 23. Ginsberg LE: Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 20(3):175–186, 1999. 24. Goncalves G, Jovem CL, Moura LO: Computed tomography of intra and extramural ethmoid cells: Iconographic essay. Radiol Bras 44(5):321–326, 2011.

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25. Hermans R: Neoplasms of the sinonasal cavities. Head and Neck Cancer Imaging. Robert Hermans, 2006, Springer, pp 191–218. 26. Hermans R, Horvath M, De Schrijver T, et al: Extranodal non-Hodgkin lymphoma of the head and neck. J Belge Radiol 77:72–77, 1994. 27. Hoang JK, Eastwood JD, Tebbit CL, et al: Multiplanar sinus CT: A systematic approach to imaging before functional sinus surgery. AJR Am J Roentgenol 194(6):W527–W536, 2010. 28. Hourany R, Aygun N, Santina CCD, et al: Silent sinus syndrome: An acquired condition. AJNR Am J Neuroradiol 26:2390–2392, 2005. 29. Huang BY, Lloyd KM, Delgaudio JM, et al: Failed endoscopic sinus surgery: Spectrum of CT indings in the frontal recess. Radiographics 29:177–195, 2009. 30. Hyams V: Papillomas of the nasal cavity and paranasal sinuses: A clinicopathologic study of 315 cases. Ann Otol Rhinol Laryngol 80:192–206, 1971. 31. Illner A, Davidson HC, Harnsberger HR, et al: The silent sinus syndrome: Clinical and radiographic indings. AJR Am J Roentgenol 178:503–506, 2002. 32. Jeon TY, Kim HJ, Chung SK, et al: Sinonasal inverted papilloma: Value of convoluted cerebriform pattern on MR imaging. AJNR Am J Neuroradiol 29:1556–1560, 2008. 33. Kadish S, Goodman M, Wang CC: Olfactory neuroblastoma: A clinical analysis of 17 cases. Cancer 37:1571–1576, 1976. 34. Kantarci M, Karasen RM, Alper F, et al: Remarkable anatomic variations in paranasal sinus region and their clinical importance. Eur J Radiol 50(3):296–302, 2004. 35. Kazkayasi M, Karadeniz Y, Aarikan OK: Anatomic variations of sphenoid sinus on CT. Rhinology 43(2):109–114, 2005. 36. Kew J, Rees GL, Close D, et al: Multiplanar reconstructed computed tomography images improve depiction and understanding of the anatomy of frontal sinus and recess. Am J Rhinol 16(2):119–123, 2002. 37. Khattar VS, Hathiram BT: Radiologic appearances of fungal sinusitis. Otorhinolaryngology clinics: An international journal. 1(1):15–23, 2009. 38. Lee HM, Kang HJ, Lee SH: Metastatic renal cell carcinoma presenting as epistaxis. Eur Arch Otorhinolaryngol 262:69–71, 2005. 39. Liang EY, Lam WW, Woo JK, et al: Another CT sign of sinonasal polyposis: Truncation of the bony middle turbinate. Eur Radiol 6(4):553–556, 1996. 40. Lohrmann C, Uhl M, Warnatz K, et al: Sinonasal computed tomography in patients with Wegener’s granulomatosis. J Comput Assist Tomogr 30:122–125, 2006. 41. Madani G, Beale TJ: Sinonasal inlammatory disease. Semin Ultrasound CT MR 30:17–24, 2009. 42. Mafee MF: Nonepithelial tumors of paranasal sinuses and nasal cavity. Radiol Clin North Am 31:61-75-90, 1993. 43. Mahmud MB, Ilica TA, Maluf F, et al: The many faces of fungal disease of the paranasal sinuses : CT and MR indings. Diagn Interv Radiol 19:195–200, 2013. 44. McLaughlin RB, Jr, Rehl RM, Lanza DC: Clinically relevant frontal sinus anatomy and physiology. Otolaryngol Clin North Am 34(1):1–22, 2001. 45. Meyer Tk, Kocak M, Smith MM, et al: Coronal CT analysis of frontal cells. Am J Rhinol 17:163–168, 2003. 46. Mohammadi HA, Haery C: Fibro-osseus lesions of cranio-facial bones—Role of imaging. Radiol Clin North Am 31:121–134, 1993. 47. Momeni AK, Roberts CC, Chew FS: Imaging of chronic and exotic sinonasal disease : A review. AJR Am J Roentgenol 189:S35–S45, 2007. 48. Muhle C, Reinhold-Keller E, Richter C, et al: MRI of the nasal cavity, the paranasal sinuses and orbits in Wegener’s granulomatosis. Eur Radiol 7(4):566–570, 1997. 49. Mukherji SK, Figueroa RE, Ginsberg LE, et al: Allergic fungal sinusitis : CT indings. Radiology 207:417–422, 1998. 50. Nouraei SA, Elisay AR, Dimarco A, et al: Variations in paranasal sinus anatomy: Implications for the pathophysiology of chronic rhinosinusitis and safety of endoscopic sinus surgery. J Otolaryngol Head Neck Surg 38(1):32–37, 2009. 51. Pasquini E, Sciaretta V, Farneti G, et al: Inverted papilloma: Report of 89 cases. Am J Otolaryngol 25:178–185, 2004.

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52. Pathria MN, Blaser SI: Diagnostic imaging of craniofacial fractures. Radiol Clin North Am 27:839–853, 1989. 53. Phillips CD: Current status and new developments in techniques for imaging the nose and sinuses. Otolaryngol Clin North Am 30(3):371–387, 1997. 54. Reddy UDMA, Dev Bhawna: Pictorial essay: Anatomical variations of paranasal sinuses on multidetector CT–How does it help FESS surgeons. Indian J Radiol Imaging 22(4):317–324, 2012. 55. Roobottom CA, Jewell FM, Kabala J: Primary and recurrent inverting papilloma: Appearances with MRI. Clin Radiol 50:472–475, 1995. 56. Saravanan K, Panda NK, Chakrabarti A, et al: Allergic fungal rhinosinusitis: An attempt to resolve the diagnostic dilemma. Arch Otolaryngol Head Neck Surg 132(2):173–178, 2006. 57. Sargi ZB, Casiano RR: Surgical anatomy of the paranasal sinuses. In Kountakis SE, Önerci M, eds: In Rhinologic and Sleep Apnea Surgical Techniques, Berlin Heidelberg, 2007, Springer, pp 17–25. 58. Schubert MS: Allergic fungal sinusitis. Otolaryngol Clin North Am 37(2):301–326, 2004. 59. Silverman CS, Mancuso AA: Periantral soft tissue iniltration and its relevance to the early detection of invasive fungal sinusitis: CT and MR indings. AJNR Am J Neuroradiol 19(2):321–325, 1998. 60. Sirikci A, Bazavit YA, Bayram M, et al: Variations of sphenoid and related structures. Eur Radiol 10(5):844–848, 2000. 61. Som P: Tumors and tumor-like conditions of sino-nasal cavity. In Som P, Bergeron RT, editors: Head and Neck Imaging, ed 4, St. Louis, 2003, Mosby, pp 261–373. 62. Som PM, Brandwein MS: Inlammatory diseases. In Som PM, Curtin DC, editors: Head and Neck Imaging, ed 4, St. Louis, 2003, Mosby, pp 193–259. 63. Som PM, Curtin HD: Inlammatory lesions and tumors of the nasal cavities and paranasal sinuses with skull base involvement. Neuroimaging Clin N Am 4:499–513, 1994.

64. Som PM, Lidov M, Brandwein M, et al: Sinonasal esthesioneuroblastoma with intracranial extension: Marginal tumor cysts as a diagnostic MR inding. AJNR Am J Neuroradiol 15(7):1259–1262, 1994. 65. Som PM, Shugar JMA: Anatomy and physiology. In Som PM, Curtin DC, editors: Head and Neck Imaging, ed 4, St Louis, 2003, Mosby, pp 87–148. 66. Sonkens JW, Harnsberger HR, Blanch GM, et al: The impact of screening sinus CT on the planning of functional endoscopic sinus surgery. Otolaryngol Head Neck Surg 105(6):802–813, 1991. 67. Stackpole SA, Edelstein DR: The anatomic relevance of the Haller cell in sinusitis. Am J Rhinol 11:219–223, 1997. 68. Stringer SP, Ryan MW: Chronic invasive fungal rhinosinusitis. Otolaryngol Clin North Am 33(2):375–387, 2000. 69. Syrjanen K, Syrjanen S: Detection of human papillomavirus in sinonasal papillomas: Systematic review and meta-analysis. Laryngoscope 123:181–192, 2013. 70. Tart RP, Mukherji SK, Avino AJ, et al: Facial lymph nodes: Normal and abnormal CT appearance. Radiology 188:695–700, 1993. 71. Weber AL: Imaging of cysts and odontogenic tumors of the jaw: Deinition and classiication. Radiol Clin North Am 31:101–120, 1993. 72. Yang C, Talbot JM, Hwang PH: Bony abnormalities of the paranasal sinuses in Wegener’s granulomatosis. Am J Rhinol 15(2):121–125, 2001. 73. Yoon JH, Na DG, Byun HS, et al: Calciication in chronic maxillary sinusitis: Comparison of CT indings with histopathologic results. AJNR Am J Neuroradiol 20:571–574, 1999. 74. Younis RT, Anand VK, Davidson B: The role of computed tomography and magnetic resonance imaging in patients with sinusitis with complications. Laryngoscope 112(2):224–229, 2002. 75. Yousem DM, Fellows DW, Kennedy DW, et al: Inverted papilloma: Evaluation with MR imaging. Radiology 185:501–505, 1992. 76. Zinreich SJ, Abayram S, Benson ML, et al: The osteomeatal complex and functional endoscopic surgery. In Som PM, Curtin HD, editors: Head and Neck Imaging, ed 4, St. Louis, 2003, Mosby, pp 149–174.

24 Cervical Adenopathy and Neck Masses Sotirios Bisdas, Katarina Surlan-Popovic, and Thomas J. Vogl

CLASSIFICATION Cancer of the head and neck, which includes cancers of the larynx, nasal passages and nose, oral cavity, pharynx, salivary glands, buccal regions, and thyroid, is the sixth most frequent cancer worldwide.78 Neck masses can be grouped into two major types: nodal masses and nonnodal masses. Both types can appear as benign or malignant lesions. Most malignant nonnodal masses are epithelial malignancies of the mucous membranes of the upper aerodigestive tract, known as head and neck squamous cell carcinoma (SCC). A second major group of head and neck nonnodal masses arises from the glandular tissue, including thyroid and salivary glands. Less frequent head and neck nonnodal neoplasms include soft tissue and bone tumors (e.g., sarcomas), neuroectodermal tissue tumors (e.g., paragangliomas, malignant melanomas), and skin cancer (e.g., SCC, basal cell carcinoma).

EPIDEMIOLOGY Chronic consumption of alcoholic beverages and smoking are accepted risk factors for head and neck cancer. In the upper aerodigestive tract, local morphologic, metabolic, and functional alterations lead to increased susceptibility to carcinogens and cell proliferation in the mucosa, resulting in genetic changes with the development of dysplasia, leukoplasia, and carcinoma. Also, radiation exposure is an established environmental factor for the development of glandular neoplasia. Nodal masses in the head and neck result from regional metastases of malignant lesions of the head and neck or represent reactive enlargement due to inlammatory lesions or benign neoplasms. Lymphoma of the head and neck also presents with enlarged nodes. Cervical node metastases have variable incidence rates, and their presence is associated with a decrease in global survival to roughly half of affected patients; in addition, they are associated with higher recurrence rates.62

NORMAL ANATOMY Gross Anatomy The neck is composed of the posteriorly located nucha and the anteriorly located cervix. The nucha consists primarily of the vertebral column and its associated musculature, and the cervix (which also means “neck”) can be thought of as a cylinder of soft tissue whose superior extent is a line connecting the occiput and the tip of the chin and whose inferior extent parallels the course of the irst rib at the thoracic inlet.

Muscles and Bones. The most important landmarks to be grossly identiied when one is studying the neck in any plane are the sterno-

cleidomastoid muscle and the hyoid bone. The sternocleidomastoid muscle takes its origin from the mastoid tip and digastric notch at the skull base and extends anteriorly, inferiorly, and medially on each side to insert as two heads on the medial third of the clavicle and the manubrium. The course of the sternocleidomastoid muscle divides the soft tissues of the neck into two paired spaces, the anterior triangles and the posterior triangles (one on each side) (Fig. 24-1). All structures located anterior to the sternocleidomastoid muscle lie within the anterior triangles, and structures deep and posterior to it are in the posterior triangles. The anterior triangles have a common side abutting each other in the midline, and their superior border is the mandible. The hyoid bone divides these triangles into a suprahyoid portion and an infrahyoid portion. The suprahyoid division contains the laterally located submandibular triangles and the medially located submental triangle. Superiorly these triangles are separated from the oral cavity by the mylohyoid muscle. By deinition, structures above the mylohyoid muscle are in the oral cavity; those below are in the neck. The base of each submandibular triangle is formed by the body of the mandible. The other two sides of each submandibular triangle are formed by the anterior and posterior bellies of the digastric muscle. The digastric muscle takes its origin from a depression on the skull base between the mastoid tip and the styloid process known as the digastric notch. The posterior belly of the digastric muscle extends anteriorly, inferiorly, and medially from the digastric notch to the greater cornu of the hyoid bone. The anterior belly of the digastric muscle extends from the greater cornu anteriorly, superiorly, and medially to insert on the internal surface of the mandible inferior to the attachment of the mylohyoid muscle. The base of the submental triangle is formed by the hyoid bone. The other two sides of the submental triangle are formed by the anterior bellies of the digastric muscles. The infrahyoid division of each anterior triangle is divided by the superior belly of the omohyoid muscle into two parts, the carotid triangle superolaterally and the muscular triangle inferomedially. The infrahyoid portion of the anterior triangle contains the larynx, hypopharynx, trachea, esophagus, lymph nodes, and thyroid and parathyroid glands. The two sides of each posterior triangle are the sternocleidomastoid muscle anteriorly and the trapezius muscle posteriorly. The base of each triangle is formed by the clavicle. The inferior belly of the omohyoid muscle crosses the inferior aspect of the posterior triangle and divides it into two unequal parts, the occipital triangle superiorly and the subclavian triangle inferiorly. The major structures located within the occipital triangle are the spinal accessory nerve (cranial nerve XI) and its associated chain of lymph nodes. The major structures located within the subclavian triangle are the transverse cervical vessels and their associated chain of lymph nodes.

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1 B

4a

A

2 C 4b

3 5

D

E 6

5

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M

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FIG 24-1 Triangles of the neck. A, Submental triangle; B, submandibular triangle; C, carotid triangle; D, muscular triangle; E, occipital triangle; F, subclavian triangle. 1, Anterior belly of the digastric muscle; 2, posterior belly of the digastric muscle; 3, superior belly of the omohyoid muscle; 4, inferior belly of the omohyoid muscle; 5, sternocleidomastoid muscle; 6, trapezius muscle. (Modiied from Reede DL, et al: CT of the soft tissue structures of the neck. Radiol Clin North Am 22:239, 1984.)

Fasciae and Spaces of the Neck. Interest in the fasciae of the neck stems from early anatomic investigations performed by surgeons who were seeking ways to predict the spread of infection. The importance of the fasciae of the neck lies in their ability to limit the spread of infections and some tumors. There is no consistent deinition of what constitutes fascia, so there are varied descriptions of the anatomic boundaries of the fasciae (Figs. 24-2 and 24-3).18,47,51 Traditionally there are two major cervical fasciae, the supericial cervical fascia (SCF) and the deep cervical fascia (DCF). Superficial cervical fascia. The SCF is a layer of fatty loose connective tissue that covers the head, face, and neck and contains the thin platysma muscles, the muscles of facial expression, the subcutaneous nerves and lymphatics, and portions of the anterior and external jugular veins. Its primary function is to allow the skin to glide easily over the deeper structures of the neck. Infections that track along the SCF are often secondary to skin infections and rarely track deeper into the neck. Deep cervical fascia. The DCF is made up of thinner but denser, better-deined layers and extends in the neck below the skull base and encloses the muscles of the neck, the mandible, and the muscles of mastication and deglutition. It consists of three layers: (1) the supericial (or investing) layer (SLDCF) surrounding all the important structures of the neck; (2) the middle layer, with the pretracheal and visceral layers (MLDCF) surrounding the aerodigestive tract; and (3) the deep layer (DLDCF) surrounding the vertebral column and paravertebral muscles. The DLDCF has two divisions separated by a potential space: the alar layer anteriorly and the prevertebral layer posteriorly. All three layers are closely associated in the anterolateral neck, where they contribute to the formation of the carotid sheath, which surrounds the carotid artery, internal jugular vein, and vagus nerve. Superficial layer of the deep cervical fascia. The SLDCF is attached posteriorly to the ligamentum nuchae and the spinous processes of the cervical vertebrae. As it extends anteriorly the fascia splits

1

FIG 24-2 The layers of deep cervical fascia and the cervical spaces, sagittal view. Solid line, investing fascia; dotted line, visceral fascia; dashed line, prevertebral fascia. 1, Suprasternal space of Burns; 2, visceral space; 4a, retrovisceral component of the retropharyngeal space; 4b, danger space; 5, prevertebral space; M, mylohyoid muscle; THY, thyroid gland. (Adapted from Smoker WRK, Harnsberger HR: Normal anatomy of the neck. In Som PM, Bergeron RT, editors: Head and neck imaging, ed 2, St. Louis, 1990, Mosby Year Book, pp 498–518.) STR THY TR E 2 4

CCA IJV SCM

3

5

TRP

FIG 24-3 The layers of deep cervical fascia and the cervical spaces of the infrahyoid neck, axial view. Solid line, investing fascia; dotted line, visceral fascia; dashed line, prevertebral fascia. 2, Visceral space; 3, carotid space; 4, retropharyngeal space; 5, prevertebral space; CCA, common carotid artery; E, esophagus; IJV, internal jugular vein; SCM, sternocleidomastoid muscle; STR, strap muscles; THY, thyroid gland; TR, trachea; TRP, trapezius muscle. (Adapted from Smoker WRK, Harnsberger HR: Normal anatomy of the neck. In Som PM, Bergeron RT, editors: Head and neck imaging, ed 2, St. Louis, 1990, Mosby Year Book, pp 498–518.)

CHAPTER 24 to envelop the trapezius and sternocleidomastoid muscles, crossing the posterior triangle of the neck. In the suprahyoid neck, the SLDCF passes over the muscles below the loor of the mouth, splits to surround the submandibular glands, and when it reaches the mandible, divides into supericial and deep lealets that enclose the muscles of mastication and form the masticator space. The SLDCF is attached superiorly to the external occipital protuberance, mastoid process, and skull base. In the infrahyoid neck, the SLDCF encircles the strap muscles (sternothyroid, sternohyoid, and thyrohyoid muscles) anterior to the larynx and trachea (although some authors believe this fascia is part of the MLDCF). The fascia also invests the omohyoid muscle, holding the muscle close to the clavicle so that contraction of the muscle results in a downward rather than a lateral pull on the hyoid bone. Caudally in the midline the SLDCF splits into two layers enclosing the manubrium. This creates the variably sized suprasternal space of Burns (or Gruber), which contains fat and a communicating vein between the left and right anterior jugular veins. If this space is entered during a tracheostomy, inadvertent transection of the communicating vein may result in considerable blood loss. Caudally the SLDCF is attached into the pectoral and axillary regions. Middle layer of the deep cervical fascia. The MLDCF is the most arbitrarily described of the fascial layers. The MLDCF in the infrahyoid neck is most commonly considered the fascia between the sternocleidomastoid muscles, passing behind the strap muscles and lying in front of the thyroid gland and trachea (many authors consider this loose connective tissue about the trachea and thyroid gland not to be part of the MLDCF). The deepest portion of the MLDCF is closely adherent to the muscular walls of the pharynx and esophagus and extends ventrally via the pterygomandibular raphe over the buccinator muscles (buccopharyngeal fascia). Inferiorly the MLDCF extends behind the sternum into the origin of the strap muscles and fuses into the ibrous pericardium (at about the level of the fourth thoracic vertebra), forming the anterior border of the retropharyngeal space. Cranially the MLDCF fuses with the thyroid cartilage and the hyoid bone, and laterally it contributes to the carotid sheath on either side of the neck. The MLDCF in the suprahyoid neck extends from the skull base and follows the outer surface of the pharyngobasilar fascia (cranial continuation of the superior pharyngeal constrictor muscle) and the pharyngeal constrictors. Here the fascia is irmly adherent to the muscular wall of pharynx and esophagus, although some authors argue for the existence of a potential visceral space between the fascia and the viscera. Deep layer of the deep cervical fascia. The DLDCF, like the SLDCF, begins in the posterior midline and extends to the side, covering and investing the muscles that form the loor of the posterior triangle. The deep layer is attached laterally to the posterior tubercles of the transverse processes of the vertebrae, where it splits into the anterior alar and posterior prevertebral layers as they extend anterior to the vertebral body (between them lies a layer of loose connective tissue). The alar and prevertebral layers have different craniocaudal extensions. Although both attach superiorly at the skull base, the alar layer blends with the visceral layer along the posterior margin of the esophagus at the level between the sixth cervical and fourth thoracic vertebrae; the prevertebral layer extends from the skull base to the coccyx. The proximal portion of each phrenic nerve lies deep to the prevertebral fascia on the anterior face of each anterior scalene muscle. On each side of the neck, the DLDCF extends laterally from the transverse process of the seventh cervical vertebra, covers the dome of the pleura, and attaches to the rib medially. This fascia separates the lower neck from the thorax and is called Sibson’s fascia.

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Neck spaces. The three layers of the DCF delineate spaces in and through which bacterial infections can spread in the infrahyoid neck. Visceral space. The visceral space includes all structures within the conines of the MLDCF (pharynx, cervical esophagus, trachea, thyroid gland, parathyroid glands, larynx, recurrent laryngeal nerves, and portions of the sympathetic trunk) and is continuous with the anterior mediastinum.4 It is considered to have two subdivisions: an anterior pretracheal space and a more posterior retrovisceral space (see later), which communicate freely around the sides of the larynx, the lowermost pharynx, and the upper cervical esophagus between the levels of the thyroid cartilage and the inferior thyroid artery. Caudal to this level, the pretracheal space is separated from the retrovisceral space by dense connective tissue. The posterior margin of the retrovisceral space is the alar layer of the DLDCF. Retropharyngeal space. The retropharyngeal space is situated in the midline directly posterior to the pharynx.18 The anterior boundary of the retropharyngeal space is formed by the MLDCF fascia, and the posterior boundary is formed by the DLDCF. The retropharyngeal space can be further divided by the alar layer of the DLDCF into the retrovisceral space anteriorly and the danger space posteriorly. Depending on its location, infection in the retropharyngeal space can extend inferiorly in the retrovisceral and pretracheal space (it is common that a retropharyngeal abscess can affect the thyroid gland and anterior mediastinum) to the level of approximately C7 (where the alar layer and the visceral layer fuse) or in the danger space just above the level of the diaphragm, where the fused alar and visceral fasciae fuse with the prevertebral fascia. Because the danger space is a closed one, the infection must penetrate its walls to enter the space. Because it is impossible to separate these two smaller spaces radiographically, the retropharyngeal space may be considered a single radiographic space, with the recognition that all infections in the retropharyngeal space must be evaluated in full, and scans of either the superior mediastinum or entire chest may be necessary (Fig. 24-4). Prevertebral space. The vertebral space is a potential space that includes those structures (vertebral bodies, paravertebral and scalene muscles, vertebral arteries) that are surrounded by the DLDCF. Infections of the prevertebral space are usually secondary to vertebral infection (osteomyelitis) or posterior extension arising in the retropharyngeal space. The vast majority of the pathology that affects this space arises from the adjacent vertebral bodies, disks, and nerves. Carotid space. The carotid space is a potential space within the carotid sheath.71 Investigators doubt whether this cavity can act as a space that allows spread of infections. Furthermore, because little areolar tissue is present within the sheath, actual infection of the carotid space is rare. The most accepted theory is that the carotid sheath may be a true space only below the carotid bifurcation and above the root of the neck. Similarly there is controversy over whether the carotid sheath in the suprahyoidal neck should be considered a separate “carotid space” or part of the parapharyngeal space. We support the latter opinion, which follows the anatomic and surgical literature. Remarkably the carotid sheath, with its contributions from all three layers of the deep cervical fascia, can act as a conduit of infection from one space to another. Septic or reactive thrombosis of the internal jugular vein may produce swelling within the carotid space. The internal jugular vein and its associated chain of lymph nodes closely parallel the deep surface of the anterior margin of the sternocleidomastoid muscle, thereby bridging the anterior and posterior triangles. The arterial and neural components of the carotid sheath, common carotid artery, internal carotid artery, and vagus nerve also traverse the neck within the anterior triangle. Body of the mandible. Another space in the suprahyoid neck is the space of the body of the mandible, which is conined by the deep

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Sectional Anatomy

*

* * *

T3

FIG 24-4 Retropharyngeal space abscess. Sagittal T2-weighted MRI demonstrates a hyperintense mass in the retropharyngeal space (asterisks) with anterior displacement of the airway. The abscess extends inferiorly to the level of the third thoracic vertebra (T3), implying involvement of the retrovisceral space rather than the danger space. (From Holliday RA, Prendergast NC: Imaging inlammatory processes of the oral cavity and suprahyoid neck. Oral Max Surg Clin North Am 4:215, 1992.)

lealet of the SLDCF on the lingual surface of the mandible along the line of origin of the mylohyoid muscle and the lingual cortex of the mandible. This potential space is limited anteriorly by the attachment of the anterior belly of the digastric muscle and posteriorly by the attachment of the internal pterygoid muscle. Submandibular space. The submandibular space is the uppermost boundary of the neck as it extends from the hyoid bone to the mandible. The mucosa in the loor of the mouth is its cranial border. The space is divided into an upper (sublingual space) and lower portion by the mylohyoid muscle. The portions communicate freely around the dorsal margin of the muscle. The submandibular gland is folded around the back of this muscle, lying partially above and partially below its dorsal edge. The radiologist should also identify whether a tumor is in the sublingual space, because that will eventually lead to an intraoperative sacriice of the lingual nerve (trigeminal nerve branch that carries the taste ibers of the anterior two thirds of the tongue) and hypoglossal nerve, which runs from the loor of the mouth to the tongue base. Other radiographically important anatomic landmarks of the above-described spaces are the deep portion of the submandibular gland and the submandibular duct (Wharton’s duct) in the sublingual space and the anterior belly of the digastric muscle, the supericial portion of the submandibular gland, and the lymph nodes in the submandibular space. The above-mentioned submental and submandibular triangles of the neck are the supericial landmarks that correspond to the lower portion of the submandibular space.

The sternocleidomastoid muscle is a constant landmark that can always be identiied on axial computed tomography (CT) scans or magnetic resonance imaging (MRI) through the neck. As one progresses from superior to inferior, the location of the sternocleidomastoid muscle moves from a far lateral position to a paramedian position. With this change in position of the sternocleidomastoid muscle, a change in relative sizes of the anterior and posterior triangles can be identiied. Superiorly the anterior triangle occupies the majority of the cross-sectional area of the neck because there is little space between the sternocleidomastoid and trapezius muscles. Inferiorly the posterior triangle occupies the majority of the cross-sectional area of the neck because there is little space between the anterior surface of the sternocleidomastoid muscle and the midline. The mylohyoid muscle, the major landmark separating the oral cavity from the suprahyoid neck, is readily identiied on both coronal and axial images. On axial images (Fig. 24-5A and B), the muscle appears in cross section as two separate muscle bundles medial to the mandible. As axial images are obtained from superior to inferior, the distance between the separate bundles decreases. The superior aspect of the submandibular gland is identiied on axial images at the posterior margin of the mylohyoid muscle. On coronal images, the muscle has the coniguration of a hammock suspended from the medial (lingual) surface of the mandible (see Fig. 24-5C and D). Immediately inferior to the mylohyoid muscle, the anterior bellies of the digastric muscle can be identiied (Fig. 24-6). Depending on the degree of angulation used on axial imaging, varying amounts of mylohyoid muscle can be seen projecting between the anterior bellies of the digastric muscle. The posterior belly of the digastric muscle can usually be identiied medial and posterior to the parotid gland, separating the gland from the contents of the carotid sheath. The hyoid bone is the major bony landmark of the anterior neck. The hyoid is best identiied on axial CT images, where its central body and greater horns (cornua) appear in the midline as an inverted U approximately at the level of the C3-C4 disk space (Fig. 24-7). The carotid bifurcation is typically located at or near the level of the hyoid bone. Separation of the larynx into the supraglottis, glottis, and subglottis seems fundamental for the interpretation of scans of patients with laryngeal cancer. The supraglottis includes the false vocal cords, arytenoids, epiglottis, and aryepiglottic folds. The glottis includes the true vocal cords, the anterior and posterior commissures, and the vocal ligament extending from the arytenoid cartilage to the thyroid cartilage. The laryngeal ventricle, which is supposed to separate the supraglottis and glottis, is itself a part of the supraglottis. Finally, the subglottis begins 1 cm below the ventricle and extends to the irst tracheal ring. The thyroid cartilage has an inverted V appearance on axial images (Fig. 24-8). The superior third of the cartilage is not fused in the midline at the level of the thyroid notch. Immediately supericial to the two halves of the thyroid cartilage are the strap muscles. The degree and pattern of ossiication of the cartilages vary with the age and sex of the patient. Gross cartilage invasion in laryngeal cancer can be detected with CT, but nonossiied hyaline cartilage shows about the same density values as tumor on CT images. Separation of nonossiied cartilage from the overlying strap muscles and detection of intracartilaginous alterations is accomplished more easily with MRI than with CT. The superior cornua of the thyroid cartilage are easily identiied as paired calciied structures, and the inferior cornua of the thyroid cartilage articulate with the posterior aspect of the cricoid cartilage.

CHAPTER 24

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FIG 24-5 Normal sectional anatomy at the junction of the oral cavity and neck. A, Contrast-enhanced CT image at the level of the mandible. The sternocleidomastoid muscle is posterior to the parotid gland. B, T1-weighted MRI at a similar level in a different patient. Note the greater tissue contrast between the mylohyoid muscle and the submandibular gland on MRI. Coronal CT scan (C) and coronal T1-weighted MRI (D) demonstrate the anterior belly of the digastric inferior to the sling-shaped mylohyoid muscle. 1, Sternocleidomastoid muscle; 2, mylohyoid muscle; 3, submandibular gland; 4, internal jugular vein; 5, internal carotid artery; 6, posterior belly of digastric muscle; 7, parotid gland; 8, anterior belly of digastric muscle; 9, longus colli muscle.

The cricoid cartilage is the only intact ring of the larynx with a complete posterior component and has a variable degree of ossiication on axial imaging. In adult patients, the cricoid cartilage appears on CT scans as a thin rim of calciication surrounding a lucent medullary center. On T1-weighted MRI, the cricoid appears as a ring of tissue isointense to fat. The level of the cricoid cartilage also marks the point at which the omohyoid muscle crosses over the internal jugular vein. The cricoarytenoid joint is a readily recognizable structure that demarcates glottic from supraglottic and subglottic structures.

The paraglottic tissues can be separated into the preepiglottic and paraglottic fat (dark on CT scanning) and the thyroarytenoid muscle (soft tissue density on CT and intermediate T1-weighted on MRI) of the true vocal cords. The true vocal cords meet in the midline at the anterior commissure, which should be no more than 1 to 2 mm thick. The posterior commissure refers to the mucosa between the two vocal processes on the anterior surface of the arytenoid cartilage. At approximately the level of the cricoid cartilage (Fig. 24-9), the superior pole of the thyroid gland appears on axial images as a

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FIG 24-6 Normal axial anatomy of the suprahyoid neck. T1-weighted MRI in the same patient as in Figure 24-5B. The submental triangle is located between the two anterior bellies of the digastric muscle. 1, Sternocleidomastoid muscle; 2, mylohyoid muscle; 3, submandibular gland; 4, internal jugular vein; 5, internal carotid artery; 6, posterior belly of digastric muscle; 8, anterior belly of digastric muscle; 9, longus colli muscle.

triangular soft tissue structure situated between the cricoid cartilage medially and the carotid sheath structures laterally. The normal gland (owing to its iodide content) has a density of 80 to 100 Hounsield units (HU) on CT. A homogeneous gland on noncontrast CT correlates well with thyroid function. The gland enhances diffusely after application of iodinated intravenous contrast material. The latter can alter the radioactive iodine uptake measurements (i.e., in nuclear imaging) for up to 6 weeks following the application. This alteration does not happen after gadolinium application. On noncontrast T1-weighted images, the gland is homogeneous in appearance and slightly hyperintense to skeletal muscle. On T2-weighted imaging, the gland is hyperintense relative to the neck musculature. Axial and sagittal T1- and T2-weighted images (with fat saturation) as well as postcontrast axial fat-saturated T1-weighted images are essential for MRI of the thyroid and parathyroid glands. The posterior triangle of the normal supracricoid neck appears as a fat-illed cleft containing a few small soft tissue structures representing nutrient vessels, lymph nodes, and nerves. Beginning at the level of the cricoid cartilage, the anterior scalene muscle can be identiied in the medial aspect of the posterior triangle, posterior to the carotid sheath structures. The anterior scalene muscle, which arises from the transverse processes of C4-C6, is the key reference point needed to locate the major neural and vascular structures in the region. The subclavian vein is located anterior to the muscle that divides the subclavian artery in three anatomic portions. The phrenic and vagus nerves cross the root of the neck anterior to the irst portion of the subclavian artery laterally and medially of it, respectively. The anterior scalene muscle lies directly anterior to the exiting trunks of the brachial plexus. At the level of the irst tracheal ring, the brachial plexus is

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B FIG 24-7 Normal axial anatomy at the level of the hyoid bone. A, Contrast-enhanced CT scan. Note that the normal retrofacial vein or proximal external carotid artery might be mistaken for a lymph node or other mass on a noncontrast examination. B, T1-weighted MRI demonstrates the same soft tissue and vascular anatomy without intravenous contrast. 1, Sternocleidomastoid muscle; 3, submandibular gland; 4, internal jugular vein; 5, internal carotid artery; 6, external carotid artery; 7, retrofacial vein; 9, longus colli muscle.

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FIG 24-8 Normal axial anatomy at the level of the thyroid cartilages. A, CT scan. B, T1-weighted MRI. Note how the anterior margin of the sternocleidomastoid muscle is located anterior to the vertebral body. Compare with Figure 24-5B. 1, Sternocleidomastoid muscle; 2, strap muscle; 3, internal carotid artery; 4, internal jugular vein; 9, longus colli muscle.

identiied as a heterogeneous low-density or low-signal-intensity focus immediately posterior to the anterior scalene muscle.

Nodal Anatomy Forty percent of the body’s lymph nodes are located in the head and neck region, which represents about 20% of the body’s volume. Each lymph node is enclosed by a ibrous capsule, and lymph moves into a node via several lymphatic vessels and emerges by one or two efferent vessels. Fibrous septa (trabeculae) extend from the covering capsule toward the center of the node. Cortical nodules found within the sinuses along the outer region of the node are separated from each other by these trabeculae. The center, or medulla, of a lymph node is composed of sinuses and cords. Both the cortical and medullary sinuses are lined with specialized reticuloendothelial cells (ixed macrophages) capable of phagocytosis. When the lymph nodes elicit the immune response, the nodes enlarge (reactive hyperplasia). However, the morphologic analysis of the reactivity has a controversial prognostic value, probably owing to a variety of response patterns in an individual patient as well as in an individual node.50,70 Nodes that drain areas of frequent infection (e.g., jugulodigastric or submental nodes) tend to enlarge over many years relative to other cervical nodes. Normal lymph nodes have an elliptical shape whose long axis is directed parallel to the anatomic structures along which the nodes are distributed and thus cannot be shown in axial CT slices. The ratio of the longitudinal (maximum) diameter to the transverse (minimum) diameter of a lymph node is a major morphologic criterion for assessing metastatic disease. In addition the minimum diameter more closely correlates with the volume of the lymph node and is less dependent on the scan plane, and therefore it is useful for follow-up imaging. The CT attenuation of lymph nodes on noncontrast CT scans is equivalent to that of other soft tissue structures.42 The node hilum can sometimes be seen to contain a small amount of fat. Normal lymph nodes display moderate homogeneous enhancement following intravenous injection of contrast material. On MRI, lymph nodes appear homogeneous with low to intermediate precontrast T1-weighted intensity and appear at fairly high

intensity in high-resolution T2-weighted images. Moreover, lymph nodes have smooth noniniltrating margins and a slight homogeneous enhancement after gadolinium administration. High-resolution MR microimaging offers a detailed structural analysis of the nodes using microscopy coils and demonstrating medullary sinus as regions of low signal intensity and follicles as high-intensity structures; the method can effectively characterize the morphologic details of benign and metastatic nodes without using gadolinium enhancement.70 Nevertheless, microimaging is limited to the supericial nodes and requires additional time for examination and evaluation of the imaging data.

Classiication. As the pathways of node metastasis were recognized in the last century, the necessity of a nodal classiication that identiies the precise location of the nodes emerged. This is important because neoplastic lymph nodes are mainly regionally localized according to the sentinel lymph node concept. The most commonly used classiication of Rouvìere in 1938, mainly based on the supericial triangles of the neck (Fig. 24-10), was followed by that of Shah and colleagues in 1981 (Fig. 24-11), which employed a simpler level-based system to help the surgeon select the most appropriate type of nodal resection.61 The latter system can be easily transferred to the axial imaging (Fig. 24-12). Since then, further classiications such as that of the American Joint Committee on Cancer (AJCC) in 1997 and the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) have modiied and improved the initial level-based system.56 To address speciic issues raised in both the AJCC and AAO-HNS classiications and to bring to nodal classiication the anatomic detail and reproducibility of imaging the vast majority of patients currently receive, an imaging-based (CT and MRI) classiication was suggested in 1999.66 A brief presentation of this classiication is given in Box 24-1.

IMAGING TECHNIQUES Various imaging techniques are currently used in the evaluation of patients with neck masses before, during, and after treatment.21,25 Each of these imaging modalities has its own advantages and disadvantages.

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FIG 24-9 Normal axial anatomy at the level of the cricoid cartilage and inferior cornua of the thyroid cartilage. A, CT scan. The asymmetry in the diameters of the internal jugular veins is a normal variant. B, T1-weighted MRI. 1, Sternocleidomastoid muscle; 2, thyroid gland; 3, internal carotid artery; 4, internal jugular vein; 8, trapezius muscle; 9, longus colli muscle.

Parotid nodes Occipital nodes Facial nodes

Mastoid nodes Jugulodigastric node

Submandibular nodes Submental nodes External carotid artery Internal jugular chain (common carotid artery, internal jugular vein, vagus nerve)

Spinal accessory nerve Greater auricular nerve Spinal accessory chain External jugular vein Transverse cervical chain

Anterior jugular chain

FIG 24-10 Nodal chains of the neck. (Modiied from Reede DL, Bergeron RT: CT of cervical lymph nodes. J Otolaryngol 11:411, 1982.)

In most patients, especially in developed countries, CT and MRI are performed for diagnosing and staging of neck masses. In the pediatric population, ultrasonography has a special role in follow-up of nodal masses.73 Whether CT or MRI is the primary imaging modality depends on the institution, although head and neck radiologists tend to use CT for imaging of laryngeal cancer, hypopharyngeal cancer,

oropharyngeal cancer, and inlammatory lesions and also use it to complement the diagnostic evaluation of tumors with presumed bone destruction. The relative low cost of CT examinations, its wide availability, the short examination time, and the high-quality multiplanar imaging provided, as well as the higher sensitivity and speciicity regarding nodal involvement in malignant neoplasms, are indisputable

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advantages of CT over MRI. On the other hand, the relatively low soft tissue contrast resolution of CT, the need to administer iodinated contrast agents, and the severe image quality degradation caused by dental illings and other foreign objects are disadvantages of CT imaging. MRI in turn may be jeopardized by motion artifacts and orthodontic material. Whatever the admission imaging modality, the patient’s follow-up has to be performed with the same modality and the same examination protocol.

* B FIG 24-12 Sectional imaging using simpliied nodal classiication. A, Axial contrast-enhanced CT scan demonstrates bilateral lymph nodes (curved white arrows) anterior to each submandibular gland (G). They are level I (submandibular triangle) lymph nodes. Note the lucent zone of fat eccentrically located in each node (straight arrows). These zones represent prominent nodal hila. B, Axial contrast-enhanced CT scan demonstrates a homogeneous 2.5-cm diameter lymph node (asterisk) in the left posterior triangle deep to the sternocleidomastoid muscle (s) and separate from the internal jugular vein (v), internal carotid artery (a), and posterior belly of the digastric muscle (d). This is a level V (spinal accessory chain) lymph node. Asymmetry in the appearance of right and left digastric muscles is secondary to slight skewing of the patient’s head within the scanner gantry.

Computed Tomography CT may be regarded as the workhorse of head and neck imaging. There are many types of CT scanners, most of which are multislice units. Thus it is not possible to deine the optimal protocol. The ideal neck CT scan provides the best possible contrast of soft tissue (with the choice of an appropriate delay, contrast agent volume, low rate, and scanning time), allows visualization of the arterial and venous vascular structures, and provides thin multiplanar reconstructions in soft tissue and bone algorithms in an angle appropriate for evaluation of the suspected lesion.27,28,33 CT is performed with the patient supine on the scanner gantry and during quiet respiration. The patient’s head may be cushioned to avoid motion artifacts during the hot lush of contrast agent injection. The patient’s shoulders must be dropped as low as possible. In case of incremental or single spiral CT, malposition of the patient can cause artifacts that simulate disease. One common solution is to acquire images from the superior orbital rim to the hard palate with the use of gantry angulation parallel to the central skull base. Images from the alveolar ridge of the mandible to the lung apex are then obtained with a gantry angulation parallel to the body of the

mandible. If the patient’s chin is fully extended, this latter series may be obtained with a 0-degree gantry angulation. Intravenous contrast enhancement is essential for CT examinations to facilitate both tissue characterization of neck masses and separation of neck masses from normal vascular structures. Most investigators recommend a bolus of approximately 80 to 100 mL of high-density iodinated contrast material administered at a rate of 1 to 2 mL/sec and a delay of 80 to 100 sec before image acquisition, followed by a steady rapid-drip saline infusion at the same rate. Power injectors, commonly used for abdominal or thoracic CT scanning, can be readily adapted for neck CT examinations. When evaluating the neck, contiguous 5-mm-thick axial images are usually obtained from the level of the superior orbital rim to the lung apex (scanning from cranial to caudal) to reduce artifacts at the level of the thoracic inlet caused by the beam-hardening effects of the contrast agent. The ield of view must be as small as possible to enhance the spatial resolution (reconstruction of the raw data in a greater ield of view can be subsequently performed to encounter possible

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Imaging-Based Classiication for Cervical Lymph Nodes BOX 24-1

I Submental and submandibular nodes, located above the hyoid bone, below the mylohyoid muscle, and anterior to the back of the submandibular gland Ia Submental nodes Ib Submandibular nodes II Upper internal jugular nodes, lying from the skull base to the level of the bottom of the body of the hyoid bone, posterior to the back of the submandibular gland, and anterior to the back of the sternocleidomastoid muscle IIa Nodes anterior, medial, lateral, and posterior to the internal jugular vein IIb Nodes posterior to the jugular vein, with a fat plane separating them from the vein III Midjugular nodes, located from the level of the bottom of the hyoid bone to the level of the bottom of the cricoid arch, anterior to the back of the sternocleidomastoid muscle IV Low jugular nodes, lying from the level of the bottom of the cricoid arch to the level of the clavicle, lateral to the carotid arteries V Nodes in the posterior triangle, lying posterior to the back of the sternocleidomastoid muscle from the skull base to the level of the bottom of the body of the cricoid arch and posterior to a line connecting the back of the sternocleidomastoid muscle and the posterolateral margin of the anterior scalene muscle from the level of the bottom of the cricoid arch to the level of the clavicle. They also lie anterior to the anterior edge of the trapezius muscle. Va Upper level V nodes, located from the skull base to the level of the bottom of the body of the cricoid arch Vb Lower level V nodes, located from the level of the bottom of the cricoid arch to the level of the clavicle. VI Upper visceral nodes, lying between the carotid arteries from the level of the bottom of the hyoid bone to the level of the top of the manubrium VII Superior mediastinal nodes, lying between the carotid arteries from the level of the top of the manubrium to the level of the innominate vein Supraclavicular nodes lie at or caudal to the clavicles and lateral to the carotid artery. Retropharyngeal nodes lie within 2 cm of the skull base, medial to the internal carotid arteries. From Som PM, et al: An imaging-based classiication for the cervical nodes designed as an adjunct to recent clinically based nodal classiications. Arch Otolaryngol Head Neck Surg 125:388–396, 1999.

pathologic conditions in these regions). The images are reconstructed in 3-mm slices for evaluation of the oropharynx (parallel to the hard palate on the axial section and coronal to the mouth loor) and 2-mm slices for evaluation of the hypopharyngeal-laryngeal region (parallel to the vocal cords as well as vertical to them). In cases of extended osteolytic lesions, three-dimensional (3D) imaging provides valuable information to surgeons. A signiicant advantage of the fast image acquisition of multislice CT scanners is the easier performance of a dynamic maneuver during the examination. Such maneuvers are the [i]-phonation (for better visualization of the laryngeal ventricle) and the modiied Valsalva (for better visualization of the pyriform sinuses, postcricoid region, and gingivobuccal tumors). CT imaging techniques that can complement the standard CT study include dynamic acquisition of neck mass sections during administration of the bolus of contrast agent. The morphologic information obtained by cross-sectional imaging of SCC of the upper

aerodigestive tract is often insuficient because of the highly iniltrative character of the tumor, posttherapy edema or ibrosis, and the dificulty of reliably recognizing lymph node metastases in apparently “normal” lymph nodes. Perfusion CT, based on various tracer kinetic models, aims at measurement of tissue blood supply, tissue vascularity, and contrast clearance. Because every neoplasm is characterized by neovascularity and increased angiogenic activity, perfusion CT is a potential imaging tool of tumor activity, theoretically before the tumor proceeds in a gross anatomic distortion.7

Magnetic Resonance Imaging MRI of the neck is routinely performed at magnetic ields of 1.5 tesla (T) and recently at 3.0 T. Possibly more important than ield strength is the choice of the right surface coils and their optimal positioning, along with comfortable positioning of the patient and instructions to avoid any movement, coughing, and swallowing during the examination. Usually the choice of the appropriate coil depends on the speciic organ or lesion being imaged; however, in our opinion the combined head-neck coil should be used every time a neck MRI study is performed. This ensures a comprehensive evaluation of the entire extracranial head and neck—evaluating all nodal masses, a second primary neoplasm, and perineural tumor spread. The possible drawback of inhomogeneous recipient ield characteristics at the crossover between the two coils is of minor importance and can be partially overcome by shimming—improved coils with identical receiver coil elements—and sequences with short echo trains. A conventional MR survey is performed using a dedicated headand-neck circular polarization surface coil and (at the beginning) performing a localizer in three planes. The axial plane is aligned along the patient’s hard palate which in turn has to be perpendicular to the tabletop. The slices should be 3 to 4 mm with either no interslice gap or a 10% interslice gap. The entire neck should be studied to evaluate lymphadenopathy, especially in patients with esophageal or thyroid cancer who present with superior mediastinal node metastases. The ield of view may be approximately 20 to 22 cm and the matrix, if possible, 512 × 512 (256 × 256) pixels. Inversion recovery fast-spin echo (FSE) sequences with fat saturation (spectral presaturation by inversion recovery [SPIR], spectral selection attenuated inversion recovery [SPAIR], and turbo inversion recovery magnitude [TIRM]) have proven useful in imaging lymph nodes by improving the conspicuity of small nodes adjacent to or surrounded by fat.58 Alternatively, contrast can be improved by performing the sequence with a chemical shift selective suppression (CHESS) technique. The FSE inversion recovery sequence can be complementary, followed by an FSE T2-weighted sequence (preferably on the axial plane). Subsequently, axial and coronal spin echo T1-weighted images are performed before and after application of gadolinium-containing contrast agent with a fat saturation in the postcontrast axial sections. Another fat saturation in the coronal plane can be renounced because the saturated images are prone to susceptibility artifacts and have a long acquisition time. Finally, the radiologist ought to avoid very fast imaging using singleshot techniques and instead take advantage of parallel imaging in high-ield scanners. In addition to conventional contrast-enhanced MRI, axial diffusionweighted imaging (DWI) may be also performed.1,39,69 DWI allows visualization as well as separation of molecular diffusion from microcirculation of the blood in the capillary network (perfusion) of biological tissues. Neoplasms are associated with alterations in water diffusivity and microcirculation of the node. DWI can be obtained with a single-shot echo planar imaging (EPI) sequence by using the same coil. The sequence can be repeated for at least three values of the motion-probing gradients (usually b = 0, 500, 700, or 1000 sec/mm2).

CHAPTER 24 Suggested section thickness is 4 to 5 mm with an intersection gap of 1 mm. Scanning time does not usually exceed 2 minutes. Quantiication of diffusion abnormalities requires calculation of the apparent diffusion coeficient (ADC). Another promising MRI technique is proton magnetic resonance spectroscopy (MRS), wherein data can be acquired on the same scanner and with the same coils that were used for the imaging.6,38 The MRI examination is used for localizing the MRS. Single-voxel spin echo sequence may be used. The echo time (TE) allows in-phase detection of the choline signal. Weak water suppression can be achieved by a CHESS technique. The volume of interest (VOI) its the size of the suspected lesion. Automatic shimming of the system is usually applied and controlled by interactive shimming by the radiologist. Postprocessing of the data includes identiication of choline and creatine metabolites. Similar to perfusion CT, dynamic MRI offers the potential of visualizing dynamically the tumor vascularity, including permeability disorders with indirect implications for tissue oxygenation status.23 EPI or a VIBE (volumetric interpolated breath-hold imaging) sequence may be used. For postprocessing of the acquired data, a semiquantitative analysis using mean signal intensity versus time curves may be performed. Parameters such as peak time (in seconds), peak enhancement (% baseline), and washout slope estimate can be calculated from the late point versus the peak point. Another approach uses commercially available deconvolution-based analysis of the dynamic data, which were irst used in perfusion studies of the brain. MRI also enables contrast material–enhanced intravenous lymphography. The irst contrast medium used for intravenous lymphography was dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles, which accumulate slowly in the phagocytes of the lymph nodes.17,41 Based on the T2* effects of the iron oxide particles, after a single intravenous administration of USPIO, T2-weighted images show areas of focal signal intensity loss in medullary sinuses corresponding to the distribution of uptake by macrophages. Lymph follicles appear unchanged in signal intensity because they are largely devoid of macrophages. Iniltration of lymph nodes with tumor alters the architecture, with tumor replacing the macrophages; hence the nodes retain their high signal intensity after USPIO administration. Several studies have demonstrated enhanced sensitivity and speciicity for lymph node evaluation after administration of USPIO particles for head and neck malignancies. However, very small lesions may go undetected because of the “blooming effect,” which relects the extreme sensitivity of T2*-weighted imaging to susceptibility artifacts. Other pitfalls of the method include the poor contrast of T2- and T2*weighted imaging between a subcapsular node metastasis and the surrounding extralymphatic tissue. Another promising lymph node–speciic contrast agent is gadoluorine M (T1 contrast agent).15 Gadoluorine M is a water-soluble paramagnetic gadolinium-based agent whose mechanism of lymph node uptake is presumed to be direct transcapillary passage through interendothelial junctions into medullary sinuses.

NODAL NECK MASSES Staging Nodal staging is concerned with the presence or absence of nodal disease, nodal size, and assessment of the involved nodes. In 1987 the AJCC and the International Union Against Cancer (UICC) developed a common staging system intended to overcome the pitfalls of subjective palpation of the nodes. The latest reinement of this staging (Box 24-2) refers to all head and neck cancers except nasopharyngeal carcinoma and thyroid carcinoma, which need separate nodal staging.

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AJCC Nodal (N) Staging System for Cervical Lymph Nodes BOX 24-2 Nx N0 N1 N2a N2b N2c N3

The lymph nodes cannot be assessed clinically. There are no metastatic lymph nodes. Single ipsilateral lymph node metastasis 3 cm or less in greatest dimension Single ipsilateral lymph node metastasis between 3 and 6 cm in greatest dimension Multiple ipsilateral lymph node metastases, none of them greater than 6 cm in greatest dimension Bilateral or contralateral lymph node metastases, none of them greater than 6 cm in greatest dimension Metastasis in lymph nodes that are more than 6 cm in greatest dimension

From Edge S, et al, editors: AJCC cancer staging manual, ed 7, American Joint Committee on Cancer, New York, 2010, Springer-Verlag.

Role of Imaging in Staging. Because invasive clinical and laboratory examinations are expensive and result in complications, radiology plays an important role in lymph node staging.75 Lymph node staging and localization of pathologic lymph nodes is mandatory for choosing therapy, either (neo) adjuvant or surgical, and is a major factor in establishing the prognosis in head and neck cancer patients.52 Nodal metastases can be categorized in two groups: overt (clinical) or nonovert (occult). Nonovert metastases may be further categorized as metastases detectable by traditional methods (e.g., staining) and as “submicroscopic” metastases, which are evident only with immunohistochemical or molecular analysis. Overt node metastases are imaged by cross-sectional imaging. The detection of nonovert metastasis is under development in that many patients initially classiied as having cN0 in fact have occult metastatic disease (pN1).40 CT and MRI evaluation must avoid false-positive results that could lead to a selective or radical neck dissection, which is associated with increased morbidity and mortality, thus overshadowing the improvement in survival. Even in the case of N0, CT and MRI play a role as close observation tools.40 Neither CT nor MRI for node staging in the neck reaches 100% sensitivity or speciicity, and the accuracy of the exact number of metastases or levels involved has not been studied.59 Thus neck dissection with subsequent pathologic examination remains the gold standard for node staging. CT and MRI aim to evaluate nodal size and shape, nodal grouping, and signs of nodal metastasis such as necrosis and extranodal tumor spread.64 The latter two criteria can be better assessed with CT imaging, although MRI does have advantages owing to the increased soft tissue contrast and the ability to obtain tissue characteristics in different sequences, including diffusion- and perfusion-weighted sequences as well as proton spectroscopy imaging. The lack of radiation burden makes MRI suitable for close follow-up of the patient, and imaging with the use of new intravenous contrast material (e.g., USPIO) seems superior to conventional imaging.

Conventional CT and MRI Findings on Neck Nodal Masses A number of diseases in addition to metastatic SCC affect the cervical lymph nodes and require imaging evaluation. These include viral, bacterial, and protozoal diseases (Toxoplasma), fungal lymphadenitides, reactive lymphadenopathies, lymphoproliferative disorders, vascular lymphadenopathies, proliferative histiocytic disorders, and

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FIG 24-13 Nonmetastatic small nodes. MRI in axial planes of nodes in level II bilaterally (arrows) in a patient with laryngeal cancer. A, Axial T2-weighted imaging shows the small nodes in level II on both sides and level V on the right side, which according to the size criterion (see text) are not metastatic. T1-weighted imaging (B) and axial TIRM-weighted images (C) also reveal no signs of nodal metastatic disease.

lymphadenopathies related to clinical syndromes such as Kimura’s disease, sarcoidosis, and Castleman’s disease. However, because imaging characteristics in all these diseases are nonspeciic, the diagnosis is based on the combination of history, clinical indings, imaging, and laboratory data. The role of imaging is to locate the node disease and evaluate any associated indings such as necrosis or abscess formation as well as soft tissue iniltration. Especially for the cervical lymph nodes, which have a major effect on the prognosis and treatment of head and neck cancer, criteria for metastatic disease include size and shape of the node, abnormality of the internal architecture (including nodal necrosis), and extracapsular tumor spread.43

Size and Shape of the Node. Size is the most frequently used criterion for diagnosis; however, sensitivity and speciicity vary widely depending on the threshold value used and the level at which the node is located (Fig. 24-13). The size criterion has long been recognized by surgeons, who initially believed that level I and level II nodes larger than 1.5 cm at their maximum diameter and that nodes elsewhere in the neck larger than 1 cm contained metastases. The inaccuracy of these criteria in about one third of cases led to reafirmation of these measurements and introduction of the minimum axial diameter of the node. These criteria suggest that the minimum diameter should not exceed 11 mm in level II nodes and should not exceed 10 mm at nodes elsewhere in the neck.22 Based on the observation that metastatic nodes tend to be spherical, whereas nonmetastatic nodes tend to be oblong or lima bean–shaped, the ratio of the maximum longitudinal length to the maximum axial nodal length was introduced.64 The ratio exceeds the value of 2 in normal hyperplastic nodes and is less than 2 in metastatic nodes. Finally, node groups with maximal diameters of 8 to 15 mm in level II or minimal diameters of 9 to 10 mm in level IV are suggestive of metastatic disease. Similarly, for three or more nodes elsewhere in the neck, the cutoff value is suggested as 8 to 9 mm. Overall it is remarkable that even if the higher value of the normal node is considered 10 mm, 16% of patients with negative imaging have metastasis. This implicates the insuficiency of nodal size alone as a criterion for diagnosis of metastases; for instance, an acceptable

negative predictive value of 90% can be achieved with a cutoff value of 6 mm. Notably the aforementioned studies are performed in homogeneous sharply differentiated nodes without taking into account any other criteria. Finally, van den Brekel and colleagues suggested a minimal axial diameter of 8 to 9 mm in level II and 7 to 8 mm for the rest of neck.76

Nodal Necrosis. Detection of nodal necrosis in untreated patients seems to be the most reliable sign of metastatic disease. Nodal necrosis appears to increase with nodal size (56%-63% of nodes >1.5 cm in diameter show necrosis), but more importantly, 10% to 33% of malignant nodes smaller than 1 cm in diameter show necrosis.19 The classic appearance of nodal necrosis on CT imaging is a low-attenuated area, whereas on MRI (fat-suppressed, T2-weighted images) it is a hyperintense area inside the node (Fig. 24-14). This MRI appearance seems to correspond to liquefaction necrosis, whereas coagulation necrosis gives a hypointense appearance relative to the residual nodal parenchyma signal. The advent of new MR scanners with surface coils and matrices with smaller pixels improved the quality of the MRI and thus revived its role in the detection of nodal necrosis,36 with diagnostic accuracy and sensitivity of 91% to 99% and 93%, respectively, which are comparable to CT rates. Overall, a distorted internal architecture seems to be a pathognomonic feature for metastatic nodes from head and neck carcinomas, whereas other investigators report distorted internal architecture to occur in 67% of metastatic nodes, 14% of lymphomas, and 9% of benign nodes.30 Considering that central nodal necrosis has a low incidence in metastatic nodes,30 it seems more reliable for the radiologist to look for distorted nodal architecture. Nevertheless, one should keep in mind the increased prevalence of heterogeneous nodal architecture (including necrosis) in nodal lymphomas (including non-Hodgkin’s disease), unlike what it was believed until recently (Fig. 24-15).35,70

Extracapsular Neoplastic Spread. Another imaging characteristic of lymph node involvement is extracapsular neoplastic spread (commonly seen in SCC as well as in lymphoma metastases), which can be

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FIG 24-16 Extranodal spread of tumor. Axial T1-weighted contrastFIG 24-14 Nodal necrosis. Axial T2-weighted MRI in the epipharynx demonstrates three metastatic lymph nodes (arrowheads) in the retropharyngeal space and in the parapharyngeal space on the left side. The inhomogeneous hyperintense signal inside the nodes corresponds with liquefaction necrosis. The patient was referred to our institution with a squamous cell carcinoma on both tonsils.

enhanced fat-saturated MR scan demonstrates an irregular interface and diffuse iniltration between the large left necrotic nodal mass and the cervical soft tissues (arrowheads). Anteriorly the overlying platysma is thickened and irregular; posteriorly the node metastasis extends in the erector spinae muscle and splenius cervicis; medially the tumor reaches the paravertebral space; laterally there is extension into the subcutaneous fat. This nodal mass was “ixed” on physical examination and appeared with an intense swelling. Note how the mass engulfs the left internal carotid artery (arrow) and the internal jugular vein cannot be recognized owing to the nodal mass effect.

well appreciated with MRI and CT. It is characterized by the presence of indistinct nodal margins, irregular nodal capsular enhancement, or iniltration in the adjacent fat or muscle (Fig. 24-16). As the node enlarges, the incidence of extracapsular spread rises and is macroscopically easy to recognize.37,76 Here, special attention must be given to the patient’s history. Recent nodal infection, surgical manipulation, and irradiation may obliterate tissue planes around vessels and lymph nodes, mimicking extracapsular spread and leading to false-positive results. The signiicance of false-positive results lies in the fact that extranodal spread is the best indicator for treatment failure and decreases survival by 50%.46 Further grave prognostic indings of metastatic nodal disease include arterial invasion to the adjacent carotid artery. Imaging of nodal microinvasion in the arterial adventitia before a gross invasion into the muscularis and intima (recognized by narrowing of the lumen) is beyond the scope and capabilities of available CT and MRI techniques. However, indings such as the degree of nodal circumferential extension and the degree of obliteration of the adjacent fat plane make arterial invasion more plausible (see Fig. 24-16). Although the survival of such patients is remarkably small, carotid artery graft replacement during the surgery may be more beneicial than tumor dissection and adjuvant chemotherapy.77 FIG 24-15 Coronal T1-weighted MRI shows a clinically palpable bilateral manifestation of nodal disease (arrows) in level III in a patient with non-Hodgkin’s lymphoma. The nodes appear to be enlarged and to have a heterogeneous architecture, which indicates metastatic disease.

Other Imaging Techniques With DWI of nodal disease, metastatic nodes show generally high signal intensity in diffusion maps (irrelevant to the b value)

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FIG 24-17 DWI of cervical nodes in a patient with non-Hodgkin’s lymphoma. A, DWI reveals a group of enlarged lymph nodes on the left side (arrow) with vivid hyperintense signal. B, The corresponding apparent diffusion coeficient map shows a uniform hypointense signal (more pronounced in the posterior larger node) indicating the restricted water diffusion in the nodes (arrow).

corresponding to low ADC values and relecting the altered architectural changes in the proportion of extracellular to intracellular water protons (Figs. 24-17 and 24-18). Necrotic areas, however, will show mixed signal intensity at different b values and high signal intensity in ADC maps (compared with the high signal intensity in T2weighted images). Therefore ADC maps provide helpful information about necrotic areas and help differentiate malignant from benign nodes.1 However, DWI fails to image readily the contours and content of small nodes (usually < 0.9 cm) because of associated susceptibility artifacts. Dynamic contrast-enhanced (perfusion) modalities may be easily integrated into any CT or MRI protocol.67 Dynamic CT acquisition presents the irst pass of contrast material through the vascular system and is used to assess perfusion and blood volume. For permeability measurements, a second phase is obtained, prolonging the acquisition up to 2 minutes. The main quantitative parameters are: BV (blood volume), expressing the volume of functional vascular network; BF (blood low) and MTT (mean transit time), presenting the rate of delivery of oxygen and nutrients; and PS (permeability surface area product), which describes the rate of contrast leakage into the extracellular space45,53 (Fig. 24-19). Furthermore, several recent studies have proven that noninvasively acquired perfusion CT parameters relect angiogenesis and can be predictive of molecular biomarkers.3,26,32 Perfusion CT technique has been demonstrated to be both precise and reproducible when applied to the study of head and neck tumor vasculature.11 Head and neck SCC and metastatic lymph nodes larger than 1 cm demonstrate increased PS, BF, BV, and decreased MTT compared with normal tissue or benign lesions.9,11,57,72 However, perfusion parameters could not differentiate between benign and malignant lymph nodes smaller than 1 cm.7 Furthermore, perfusion CT may be used for the prognosis of short- and long-term response to therapy, a parameter of major importance for patient-tailored therapeutic regimens.10,24,79 Another clinically meaningful application of dynamic cross-sectional imaging in neck masses is differentiation between posttherapeutic changes and tumor recurrence, which remains a challenging issue on

conventional CT or MRI. In a study comparing CTP parameters between recurrent tumors and posttherapy changes after chemoradiation treatment, recurrent tumor demonstrated signiicantly higher BF compared to tissue changes after chemoradiation.7 Dynamic contrastenhanced (DCE) MRI, also widely referred to as permeability MRI, is based on the acquisition of dynamic T1-weighted images during a bolus of gadolinium-based contrast agent. DCE-MRI offers superior spatial resolution and less susceptibility artifacts in the neck than dynamic susceptibility contrast-enhanced (DSC) MRI, which, however, proits from superior temporal resolution. The most frequently used metric in DCE MR perfusion is the transfer constant of contrast agent between intra- and extravascular space (Ktrans), whose value depends on blood low and permeability and therefore can be used for tumor neoangiogenesis measurements (Fig. 24-20). Studies using DCE-MRI focused on predicting values of baseline perfusion parameters in metastatic lymph nodes or primary tumor, suggesting that higher pretreatment Ktrans is predictive for short-term tumor response and local control in head and neck SCC treated with chemoradiation.31,34,49 Another functional MRI diagnostic technique that can be implemented in every MR survey for evaluation of nodal disease (with an additional acquisition time of ≈ 5 minutes) is proton MRS. Metastatic nodal disease seems to have characteristic spectra that could differentiate it from adjacent healthy tissue and immunostimulated lymph nodes, because metastatic nodes present higher choline concentrations due to the neoplastic tissue6 (Fig. 24-21). The technique seems feasible for nodal volumes up to 9 mm3; because of MRS-inherent problems (e.g., inadequate signal reception, motion artifacts, strong lipid signal, shimming), there have been a restricted number of in vivo series in the neck region. Special reference should be made to speciic imaging indings of metastatic thyroid carcinoma, which is usually of papillary or follicular type and rarely of anaplastic type. The nodal metastases may have a great variety of imaging indings, including enhancement, scattered calciications (the differential diagnosis includes lymphomas before or after irradiation or chemotherapy, tuberculosis, metastatic mucinous

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C FIG 24-18 DWI in a patient with bilateral lymphadenopathy, on the right side appearing as neck mass, due to tonsillar carcinoma. A, Fat-suppressed T1-weighted MRI shows the necrotic neck mass (asterisk) with the surrounding inlammatory reaction and extracapsular spread as well as three suspected lymph nodes on the contralateral side (arrows). B, DWI (b value 1000 s/mm2) shows residual hyperintensity on the left nodes (arrows) as well as in the right-sided neck mass, more pronounced in the necrotic (abscess-like) part. C, Calculated ADC values are markedly low, indicating metastatic nodal disease, which was histopathologically conirmed.

adenocarcinomas, prostate metastasis, the result of prior granulomatous disease, and seminomas), or even indings of a benign cyst with or without hemorrhagic areas.44 On MRI, most metastatic nodes have low to intermediate T1-weighted and high T2-weighted signal intensity. High T1-weighted signal may be seen in papillary thyroid carcinoma nodal metastases because of the high intranodal concentrations of macroglobulin. Hemorrhage will also demonstrate high intensity in both T1- and T2-weighted imaging. Miscellaneous diseases with adenopathy include Castleman’s disease (angiofollicular lymph node

hyperplasia), sarcoidosis, cat-scratch disease (caused by Bartonella henselae), and Kimura and Kikuchi diseases. Finally, the identiication of certain patterns of nodal disease facilitates clinical evaluation as follows: 1. Large homogeneous lymph nodes or “foamy”-appearing nodes, sometimes with a thin capsule, are most commonly encountered in lymphoma, sarcoidosis, and infectious mononucleosis. Cross-sectional imaging cannot reliably differentiate Hodgkin’s from non-Hodgkin’s lymphoma.

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C FIG 24-19 A, Contrast-enhanced CT imaging (early arterial phase) of a patient with an enlarged lymph node (indicated by the free-hand drawn ROI) in level 2 on the left side. The patient underwent perfusion CT, and blood volume (B) as well as permeability (C) were estimated in the lymph node of interest. Blood volume seems not signiicantly elevated, whereas permeability value is pathologically high. The histopathologic examination showed metastatic disease from ipsilateral oropharyngeal carcinoma.

2. Total or relatively uniform enhancement of an enlarged node is usually encountered in inlammatory processes. Exceptions to this rule include nodal involvement by Kaposi’s sarcoma (Fig. 24-22), thyroid carcinoma, and renal cell carcinoma (Fig. 24-23). 3. A cluster of nodes with a variety of appearances (homogeneous, necrotic, enhancing, and calciied) is most compatible with granulomatous disease of cervical lymph nodes or lymphomas (Fig. 24-24). In urban centers, tuberculosis is the most common cause54 (Fig. 24-25).

NONNODAL NECK MASSES The most common etiologies of nonnodal neck masses include congenital lesions and their complications, inlammatory lesions, vascular lesions, neural lesions, and malignant lesions. The role of the radiologist is to differentiate among these conditions using imaging modalities such as ultrasound (US) with color Doppler, CT, and MRI. CT and MRI can then be used to determine the extent of the lesion and whether local invasion is present. Both CT and MRI can provide multiplanar images, but MRI will more effectively demonstrate the soft

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FIG 24-20 DCE-MRI–derived K

measurements overlaid onto the anatomic fat-suppressed postcontrast T1-weighted images in a patient with lateral lymphadenopathy on the left side. The elevated Ktrans values in the small submental (level 1) node (A) as well as in the necrotic node (level 2) (B) indicate metastatic disease. Note the pronounced heterogeneity in the tumor microenvironment, as depicted in the different degrees of neoangiogenesis (elevated Ktrans) values on tumor rim.

Cho I: 4.21 W: 6.30 0.6

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FIG 24-21 Proton MRS of a nodal metastasis. A, Coronal T1-weighted MR scan, used as a localizer for placement of the voxel of interest, shows the extended nodal tumor on the left side with iniltration of the adjacent soft tissue. B, The spectrum of the subsequently performed MRS reveals high choline signal indicating a cell-proliferating disease. The choline-to-creatine integrals ratio is 2.6, which is in essential agreement with the published data.

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FIG 24-23 Renal cell carcinoma nodal metastasis. Coronal T1-weighted FIG 24-22 Kaposi’s sarcoma. Axial contrast-enhanced CT scan at the

MR scan demonstrates a circumscribed node on the left side (arrowheads) with heterogeneous architecture and a hypointense capsule.

level of the anterior bellies of the digastric muscles demonstrates multiple uniformly enhancing masses in the anterior and posterior triangles of the neck bilaterally, the largest identiied in the left spinal accessory chain (asterisk). Multiple oropharyngeal lesions are also present (K).

FIG 24-25 Tuberculous adenitis in an 18-year-old female patient. FIG 24-24 Sarcoidosis of cervical lymph nodes (axial contrast-enhanced fat-saturated T1-weighted MRI). A cluster of nodes (arrows) with a slightly hypointense center and an enhancing rim on the left side.

Coronal contrast-enhanced T1-weighted MR scan demonstrates a circumscribed lymph node (arrow) in the supraclavicular fossa that has a variably homogeneous and partially necrotic parenchyma without iniltrating margins.

CHAPTER 24 tissue characteristics of a lesion. The CT and MR appearances of nodal and nonnodal neck masses often overlap. Careful attention to imaging indings and correlation with clinical history are essential to establish the correct diagnosis.

Masses of Developmental Origin Congenital lesions of the neck are usually not dificult to diagnose and involve lymphangiomas (cystic hygromas), branchial cleft cysts, thyroglossal duct cysts, and (epi)dermoids.

Lymphangioma. Cystic hygroma is the most common form of lymphangiomatous malformation occurring in the neck (other types include cavernous lymphangioma, capillary lymphangioma, and vasculolymphatic malformation) (Figs. 24-26 and 24-27).2 Cystic hygroma is a nonencapsulated lymphatic rest that is left behind during embryogenesis. It typically presents at birth or within irst 2 years of life and may occasionally be associated with a more generalized failure of

S

FIG 24-26 Cystic hygroma. Axial contrast-enhanced CT scan at the level of the irst tracheal ring demonstrates a multilocular cystic mass without rim enhancement occupying the entire right posterior triangle extending toward the right axilla. S, Sternocleidomastoid muscle.

Cervical Adenopathy and Neck Masses

lymphatic system development, as is seen in cases of the 45,X chromosome karyotype (Turner’s syndrome). Its imaging appearance is that of a uniloculated or multiloculated nonenhancing mass, without signiicant mass effect, that insinuates between normal structures. Its CT appearance is a hypodense nonenhancing poorly circumscribed cystic mass. On MRI, however, it appears as a low T1-weighted and high T2-weighted signal mass with no or subtle rim enhancement, with the latter implicating venous or hemangiomatous components. Finally, hyperintensity in T1-weighted images may suggest hemorrhage. Lingual thyroid tissue can also be observed as a lobular mass in the midline sublingual space and presents with the aforementioned features. Because up to 10% of cervical cystic hygromas may extend into the mediastinum, imaging is performed to assess the extent of the lesion and its relationship to adjacent structures before surgical resection.

Branchial Cleft Cyst. Special attention has to be given to the diagnosis of the second branchial cyst (the Bailey type II cyst, which is secondary to persistence of the embryologic cervical sinus) as the most common developmental mass identiied on imaging and the most common branchial cleft anomaly.5 It appears as an intermittent soft, painless mass along the course of the anterior margin of the sternocleidomastoid muscle and affects children, teenagers, and young adults. The classic location of the second branchial cyst, which is actually a branchial apparatus remnant, is in the posterior submandibular space at the angle of mandible (Figs. 24-28 and 24-29). In contrast, the type III second branchial cleft cyst courses between the external and internal carotid arteries. The most speciic imaging characteristic of the lesion is displacement of the submandibular gland anteromedially, the carotid space medially, and the sternocleidomastoid muscle posterolaterally.73 The lesions appear cystic on CT imaging and show a bright signal on T2-weighted images. T1-weighted signal is variable depending on the protein content of the cyst. Enhancement is usually present in infected cysts, in which case cellulitis may appear in the surrounding soft tissues. Septations are uncommon and are usually found only in cases of previous infection or needle aspiration. Infected cysts may mimic

S PT

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FIG 24-27 Cystic hygroma. A, Sagittal T1-weighted MRI demonstrates a lobulated posterior triangle mass (asterisk) that is moderately hyperintense to muscle (C). B, The mass (asterisk) is located deep to the posterior margin of the sternocleidomastoid muscle (S). Note how the hygroma tracks posterior to the internal jugular vein (V). The hygroma appears virtually isointense to fat in the right posterior triangle (PT).

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necrotic jugular chain lymph nodes or cervical abscesses on both CT and MRI.

Thyroglossal Duct Cyst. The persistence of the thyroglossal duct (normally it involutes during the eighth to tenth week) gives rise to midline (75%) or paramedian (2 cm), which represent larger-caliber vessels. Rapid-low dominant tumor vessels in all sequences are thought to be speciic (in conjunction with the T2-weighted signal proile of the lesion) for the tumor, so that contrast enhancement may be unnecessary. However, other neck masses, such as nodal metastases from renal cell or thyroid carcinoma, may display areas of signal void on MRI. Some venous hemangiomas may have a similar hypervascular imaging appearance with low voids (Fig. 24-39). A key feature for the differential diagnosis is lack of displacement of the adjacent vessels. Carotid body tumors arise in the juxtahyoid neck and separate the internal and external carotid arteries on sectional imaging. Glomus vagale tumors arise in the suprahyoid neck and displace the internal carotid artery anteromedially and the internal jugular vein

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B FIG 24-37 Paraganglioma of the neck. A, Axial TIRM-weighted MRI demonstrates a heterogeneous mass (arrows) at the bifurcation of the common carotid artery splaying the external carotid artery anteriorly and the internal carotid artery posteriorly. B, Axial T1-weighted MRI at the same level demonstrates a left anterior triangle mass (arrows) with an internal anterior area of signal void.

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FIG 24-38 Paraganglioma of the neck. Sagittal MIP (maximum intensity projection) reconstruction of contrast-enhanced CT imaging demonstrates an enhancing homogeneous mass (asterisk) at the bifurcation of the common carotid artery splaying the external and internal carotid (with calciied plaques) arteries.

FIG 24-39 Venous hemangioma. Axial contrast-enhanced fat-saturated MR scan demonstrates an avidly enhancing lesion in the left submental triangle (arrowheads) without iniltration of the adjacent muscle tissue and the submandibular gland.

CHAPTER 24 posterolaterally. When there is gross asymmetry in the splaying of the internal and external carotid arteries, the possibility of a vascular-type nodal metastasis or even a schwannoma of the cervical sympathetic chain (usually lateral to the carotid vessels) should be considered. Finally, MR indings after radiation therapy of the paragangliomas include variable alteration in T2 signal, decreased heterogeneous enhancement, and a reduction in low voids.48 For imaging paragangliomas and their feeders, 3D time-of-light (TOF) MRA is superior to 3D phase-contrast angiography and 2D TOF MRA, but like CT angiography it cannot replace conventional digital subtraction angiography, especially for carotid body tumors.74

Masses of Neural Origin Schwannomas and neuroibromas are the most common types of neurogenic tumors found in the head and neck. Common sites for schwannomas and neuroibromas in the neck are the vagus nerve, less commonly the glossopharyngeal nerve, the ventral and dorsal cervical nerve roots, the cervical sympathetic chain, and the brachial plexus (Fig. 24-40). When small, schwannomas rarely cause symptoms. When they are large, associated motor dysfunction and pain in the distribution of a sensory nerve are varying clinical indings because, for example, salivary gland tumors tend to invade nerves. Because the cervical sympathetic chain runs in a relatively loose fascial compartment, compression, such as is seen in other schwannomas, is exceedingly rare. Without a clinical history of neuroibromatosis, it is impossible to distinguish between schwannomas and neuroibromas on sectional imaging. The most demanding aspect of treatment of these lesions is distinguishing the benign cervical sympathetic schwannoma from other pathology in the parapharyngeal space. The differential diagnosis of a parapharyngeal space mass is based on the division of the space into pre- and poststyloid compartments. The prestyloid compartment contains the parotid gland, fatty tissue, and lymph nodes. It has the highest incidence of tumors. The poststyloid compartment contains

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the carotid sheath with the sympathetic chain and cranial nerves IX through XII. Thus masses arising in the poststyloid compartment include carotid artery lesions, paragangliomas arising from the vagus nerve or the carotid body, neurogenic tumors involving cranial nerves IX to XII, or sympathetic chain neurogenic lesions. Most schwannomas are fairly homogeneous soft tissue masses and appear hypodense or isodense to skeletal muscle on noncontrast CT and tend to be hypointense or isointense to skeletal muscle on T1-weighted and variably hyperintense on T2-weighted MRI. Despite their hypovascularity, they enhance signiicantly on both CT and MRI and can mimic a paraganglioma. Enhancement of schwannomas is seen at least 2 minutes after contrast injection and depicts the equilibrium phase of the contrast agent and the poor venous drainage of the tumor. Dynamic scans can reveal the true nature of the lesion and differentiate it from hypervascular lesions. The enhancement pattern of neural tumors can vary; it may be an inhomogeneous enhancement (owing to necrosis and hemorrhage) or even lack of enhancement.20 There are some useful hints to establish the diagnosis of a neural tumor in the neck.65 For example, a tumor arising from the vagus nerve manifests as a mass in the anterior triangle, displacing the internal or common carotid artery anteromedially and the internal jugular vein posterolaterally (Fig. 24-41), whereas a neoplasm of the cervical nerve roots manifest as a mass in the posterior triangle, which may extend into one of the neural foramina of the cervical spine (Fig. 24-42). Sympathetic chain tumors demonstrate a constant relationship with the longus colli muscles, and lesions of the cervical sympathetic chain, as they grow and expand, tend to push the common carotid or internal and external carotids anteriorly. Brachial plexus schwannomas and neuroibromas in the infrahyoid neck often displace the anterior scalene muscle anteriorly.

Masses of Mesenchymal Origin Lipomatous tumors such as lipoma, lipoblastoma, and liposarcoma are the most common cervical neoplasms of mesenchymal origin (Fig. 24-43).63 They typically manifest as painless masses, occurring most commonly in the midline of posterior neck or the posterior triangle. Cervical lipoblastoma typically presents as a rapidly enlarging mass.13 Although they are generally asymptomatic, there are cases of lipomatous tumors with respiratory compromise, two cases of Horner’s syndrome, a case of hemiparesis, and a case of upper extremity weakness caused by compression of the spinal cord.13

AL

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FIG 24-41 Vagal schwannoma. Sagittal reconstruction of a contrastFIG 24-40 Schwannoma. Coronal contrast-enhanced MR scan demonstrates an enhancing heterogeneous mass (arrows) medial to the right sternocleidomastoid muscle in the parapharyngeal space near the skull base.

enhanced CT scan demonstrates a predominantly middle-density mass (arrows) medial to the left sternocleidomastoid muscle, without signs of soft tissue iniltration. Note the site of the schwannoma in relation to the jugular foramen at the level of the skull base.

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B FIG 24-42 Dorsal cervical nerve root schwannoma. A, Axial contrastenhanced CT scan at the level of the thyroid cartilages demonstrates a rim-enhancing solid posterior triangle mass (asterisk) deep to the left sternocleidomastoid muscle (S). On this single image, differentiation of neural tumor from enhancing lymph node would be impossible. B, Axial contrast-enhanced CT scan at the level of the hyoid bone demonstrates that the mass (asterisk) involves the neural foramen (arrows), allowing the correct radiologic diagnosis of neural tumor.

CT can be used to demonstrate the presence of a mass (homogeneous nonenhancing mass isodense to subcutaneous fat), but MRI is particularly helpful in its ability to suggest the histologic components of the tumor.55 Lipomas may or may not have a demonstrable capsule on sectional images. Lipoblastoma typically appears hyperintense on both T1- and T2-weighted images, although it is consistently less intense than mature fat on T1-weighted images, likely owing to its ibrous septa and the variable degree of lipomatous differentiation. Lipocytes, or mature fat cells, exhibit relatively high signal intensity on T1-weighted images, whereas lipoblasts show lower intensity. The degree of intensity on T2-weighted images also varies, primarily depending on the amount of myxoid and ibrous components. Myxoid stroma and lipoblasts exhibit high intensity on T2-weighted images. The technique of fat suppression sequencing is particularly valuable in the assessment of lipoblastoma in its ability to demonstrate the presence of fatty tissue even when standard T1 and T2 images fail to demonstrate suficient hyperintensity of the tumor to indicate such content. Liposarcoma is one of the most frequent malignant soft tissue tumors in adults. It should be suspected whenever a large (>5 cm) fat-containing soft tissue tumor is found, especially when it is clinically

associated with pain and rapid growth. Well-differentiated liposarcoma displays a hypointense fat intensity (≤20 HU) mass on CT; the tumor shows signal intensities similar to those of subcutaneous normal fat on MRI. Poorly differentiated liposarcoma displays tissue density on CT and low signal intensity on spin echo T1-weighted and high signal intensity on T2-weighted MRI with intense early enhancement on dynamic acquisition contrast-enhanced images. Ill-deined borders, and especially nonfatty heterogeneous content, indicate the high probability of malignant tumor. Other sarcomas that may be present are rhabdomyosarcoma, ibrosarcoma, osteosarcoma, chondrosarcoma, malignant ibrous histiocytoma, leiomyosarcoma, alveolar soft part sarcoma, Ewing’s sarcoma, and synovial sarcoma. The imaging indings of these entities frequently are nonspeciic. However, imaging, particularly MRI, has a major role in deining the extent of these tumors. This is important because complete surgical excision is the preferred method of treatment. Imaging also is useful in planning radiation therapy and determining prognosis. Sarcomas tend to destroy bone and distort soft tissue planes. The ramus of the mandible is the most common site of Ewing’s sarcoma of the head and neck. The typical manifestations are rapidly growing mass with associated pain and local paresthesias. Mandibular involvement may cause additional associated symptoms, such as loosening of teeth and otitis media. Images of Ewing’s sarcoma and osteogenic sarcoma show large soft tissue masses that originate in the marrow, permeate and destroy the cortical bone, and extend into the masticator space. The extent of bone marrow involvement is best evaluated with T1-weighted imaging, whereas T2-weighted imaging is of value for deining the margins of the tumor and its relation to neurovascular bundles and adjacent muscle. Desmoids and other benign mesenchymal tumors tend to have sharply circumscribed borders and typically do not iniltrate adjacent soft tissue or destroy bone. They may exhibit local aggressiveness in a small subset of patients. The superiority of CT in depicting cortical bone involvement is evident; however, the true extent of the iniltrative process within the trabecular bone network is better assessed with MRI showing displacement of the normal fatty marrow.

Masses Arising from the Aerodigestive Tract Masses detected on sectional images of the neck may represent cervical extensions of diseases arising within the oral cavity, larynx, or hypopharynx. A mucus-illed cyst may be present in the glossoepiglottic fold. More often a laryngocele, which presents an abnormal dilatation of the saccule (appendix) of the laryngeal ventricle, is found in crosssectional imaging (Fig. 24-44). Although a small proportion of laryngoceles are congenital, the majority are the result of chronic increases in intralaryngeal pressure. Neoplasms or localized inlammation and edema may occasionally obstruct the ventricle, and imaging is required to exclude this situation. The resulting ball-valve mechanism traps air within the saccule. Mucus produced by the respiratory epithelium of the ventricle may result in a luid-illed laryngocele (laryngeal mucocele). Internal laryngoceles are limited to the paralaryngeal space. External or combined internal and external laryngoceles extend from the paralaryngeal space into the anterior triangle of the neck via fenestrations in the thyrohyoid membrane. On CT or MRI, the external component of a laryngocele appears as a thin-rimmed luid-illed or air-illed mass directly lateral to the thyrohyoid membrane. Continuity with the internal component can be demonstrated on axial or direct coronal images. A pharyngocele is an abnormal dilatation of the pyriform sinus, which may also herniate through the thyrohyoid membrane to manifest in the anterior triangle. The less common pharyngocele is differentiated from a laryngocele by the demonstration of continuity with

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FIG 24-43 Lipoblastoma. A, Coronal T1-weighted MRI at the level of the supraglottis in an adolescent patient demonstrates a fat-intensity mass with variable degree of fat content in its center (arrow) originating from the right pyriform sinus. B, Axial contrast-enhanced fat-saturated MR scan shows a hypointense mass (arrow) after fat saturation, with enhanced wall.

the pyriform sinus rather than the laryngeal ventricle. Neoplasms or abscesses involving the apex of the pyriform sinus may extend into the anterior triangle of the infrahyoid neck through the cricothyroid membrane.

REFERENCES

FIG 24-44 Mixed (external) laryngocele. Axial contrast-enhanced fatsaturated MR scan shows an air-illed, thin-walled, space-occupying lesion in the right lower submandibular space mass (arrow).

1. Abdel Razek AA, Soliman NY, Elkhamary S, et al: Role of diffusionweighted MR imaging in cervical lymphadenopathy. Eur Radiol 16:1468–1477, 2006. 2. Ahuja AT, Wong KT, King AD, et al: Imaging for thyroglossal duct cyst: The bare essentials. Clin Radiol 60:141–148, 2005. 3. Ash L, Teknos TN, Gandhi D, et al: Head and neck squamous cell carcinoma: CT perfusion can help noninvasively predict intratumoral microvessel density. Radiology 251:422–428, 2009. 4. Babbel RW, Smoker WR, Harnsberger HR: The visceral space: The unique infrahyoid space. Semin Ultrasound CT MR 12:204–223, 1991. 5. Benson MT, Dalen K, Mancuso AA, et al: Congenital anomalies of the branchial apparatus: Embryology and pathologic anatomy. Radiographics 12:943–960, 1992. 6. Bisdas S, Baghi M, Huebner F, et al: In vivo proton MR spectroscopy of primary tumours, nodal and recurrent disease of the extracranial head and neck. Eur Radiol 17:251–257, 2007. 7. Bisdas S, Baghi M, Smolarz A, et al: Quantitative measurements of perfusion and permeability of oropharyngeal and oral cavity cancer, recurrent disease, and associated lymph nodes using irst-pass contrastenhanced computed tomography studies. Invest Radiol 42:172–179, 2007. 8. Bisdas S, Chambron-Pinho N, Smolarz A, et al: Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of indings in 32 patients. Clin Radiol 63:71–77, 2008.

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9. Bisdas S, Medov L, Baghi M, et al: A comparison of tumor perfusion assessed by deconvolution-based analysis of dynamic contrast-enhanced CT and MR imaging in patients with squamous cell carcinoma of the upper aerodigestive tract. Eur Radiol 18:843–850, 2008. 10. Bisdas S, Rumboldt Z, Surlan-Popovic K, et al: Perfusion CT in squamous cell carcinoma of the upper aerodigestive tract: Long-term predictive value of baseline perfusion CT measurements. AJNR Am J Neuroradiol 31:576–581, 2010. 11. Bisdas S, Surlan-Popovic K, Didanovic V, et al: Functional CT of squamous cell carcinoma in the head and neck: Repeatability of tumor and muscle quantitative measurements, inter- and intra-observer agreement. Eur Radiol 18:2241–2250, 2008. 12. Braun IF, Hoffman JC, Jr, Malko JA, et al: Jugular venous thrombosis: MR imaging. Radiology 157:357–360, 1985. 13. Brodsky JR, Kim DY, Jiang Z: Cervical lipoblastoma: Case report, review of literature, and genetic analysis. Head Neck 29:1055–1060, 2007. 14. Brousseau VJ, Solares CA, Xu M, et al: Thyroglossal duct cysts: Presentation and management in children versus adults. Int J Pediatr Otorhinolaryngol 67:1285–1290, 2003. 15. Choi SH, Han MH, Moon WK, et al: Cervical lymph node metastases: MR imaging of gadoluorine M and monocrystalline iron oxide nanoparticle-47 in a rabbit model of head and neck cancer. Radiology 241:753–762, 2006. 16. Chong J, Hinckley LK, Ginsberg LE: Masticator space abnormalities associated with mandibular osteoradionecrosis: MR and CT indings in ive patients. AJNR Am J Neuroradiol 21:175–178, 2000. 17. Curvo-Semedo L, Diniz M, Migueis J, et al: USPIO-enhanced magnetic resonance imaging for nodal staging in patients with head and neck cancer. J Magn Reson Imaging 24:123–131, 2006. 18. Davis WL, Smoker WR, Harnsberger HR: The normal and diseased infrahyoid retropharyngeal, danger, and prevertebral spaces. Semin Ultrasound CT MR 12:241–256, 1991. 19. Don DM, Anzai Y, Lufkin RB, et al: Evaluation of cervical lymph node metastases in squamous cell carcinoma of the head and neck. Laryngoscope 105:669–674, 1995. 20. Eldevik OP, Gabrielsen TO, Jacobsen EA: Imaging indings in schwannomas of the jugular foramen. AJNR Am J Neuroradiol 21:1139–1144, 2000. 21. Eskey CJ, Robson CD, Weber AL: Imaging of benign and malignant soft tissue tumors of the neck. Radiol Clin North Am 38:1091–1104, xi, 2000. 22. Feinmesser R, Freeman JL, Noyek AM, et al: Metastatic neck disease. A clinical/radiographic/pathologic correlative study. Arch Otolaryngol Head Neck Surg 113:1307–1310, 1987. 23. Fischbein NJ, Noworolski SM, Henry RG, et al: Assessment of metastatic cervical adenopathy using dynamic contrast-enhanced MR imaging. AJNR Am J Neuroradiol 24:301–311, 2003. 24. Gandhi D, Chepeha DB, Miller T, et al: Correlation between initial and early follow-up CT perfusion parameters with endoscopic tumor response in patients with advanced squamous cell carcinomas of the oropharynx treated with organ-preservation therapy. AJNR Am J Neuroradiol 27:101–106, 2006. 25. Gor DM, Langer JE, Loevner LA: Imaging of cervical lymph nodes in head and neck cancer: The basics. Radiol Clin North Am 44:101–110, viii, 2006. 26. Hoeling N, McHugh J, Light E, et al: Human papillomavirus, p16, and epidermal growth factor receptor biomarkers and CT perfusion values in head and neck squamous cell carcinoma. AJNR Am J Neuroradiol 34:1062–1066, 2013. 27. Huda W, Lieberman KA, Chang J, et al: Patient size and x-ray technique factors in head computed tomography examinations. II. Image quality. Med Phys 31:595–601, 2004. 28. Hudgins PA: Contrast enhancement in head and neck imaging. Neuroimaging Clin N Am 4:101–115, 1994. 29. Imhof H, Czerny C, Hormann M, et al: Tumors and tumor-like lesions of the neck: From childhood to adult. Eur Radiol 14(Suppl 4):L155– L165, 2004. 30. Ishikawa M, Anzai Y: MR imaging of lymph nodes in the head and neck. Magn Reson Imaging Clin N Am 10:527–542, 2002.

31. Jansen JF, Schöder H, Lee NY, et al: Noninvasive assessment of tumor microenvironment using dynamic contrast-enhanced magnetic resonance imaging and 18F-luoromisonidazole positron emission tomography imaging in neck nodal metastases. Int J Radiat Oncol Biol Phys 77:1403–1410, 2010. 32. Jo SY, Wang PI, Nör JE, et al: CT perfusion can predict overexpression of CXCL8 (interleukin-8) in head and neck squamous cell carcinoma. AJNR Am J Neuroradiol 34:2338–2342, 2013. 33. Keberle M, Tschammler A, Hahn D: Single-bolus technique for spiral CT of laryngopharyngeal squamous cell carcinoma: Comparison of different contrast material volumes, low rates, and start delays. Radiology 224:171–176, 2002. 34. Kim S, Loevner LA, Quon H, et al: Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging. AJNR Am J Neuroradiol 31:262–268, 2010. 35. King AD, Lei KI, Ahuja AT: MRI of neck nodes in non-Hodgkin’s lymphoma of the head and neck. Br J Radiol 77:111–115, 2004. 36. King AD, Tse GM, Ahuja AT, et al: Necrosis in metastatic neck nodes: Diagnostic accuracy of CT, MR imaging, and US. Radiology 230:720– 726, 2004. 37. King AD, Tse GM, Yuen EH, et al: Comparison of CT and MR imaging for the detection of extranodal neoplastic spread in metastatic neck nodes. Eur J Radiol 52:264–270, 2004. 38. King AD, Yeung DK, Ahuja AT, et al: Human cervical lymphadenopathy: Evaluation with in vivo 1H-MRS at 1.5 T. Clin Radiol 60:592–598, 2005. 39. Koc O, Paksoy Y, Erayman I, et al: Role of diffusion weighted MR in the discrimination diagnosis of the cystic and/or necrotic head and neck lesions. Eur J Radiol 62:205–213, 2006. 40. Layland MK, Sessions DG, Lenox J: The inluence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N. Laryngoscope 115:629–639, 2005. 41. Mack MG, Balzer JO, Straub R, et al: Superparamagnetic iron oxideenhanced MR imaging of head and neck lymph nodes. Radiology 222:239–244, 2002. 42. Mancuso AA, Harnsberger HR, Muraki AS, et al: Computed tomography of cervical and retropharyngeal lymph nodes: Normal anatomy, variants of normal, and applications in staging head and neck cancer. Part I: Normal anatomy. Radiology 148:709–714, 1983. 43. Mancuso AA, Harnsberger HR, Muraki AS, et al: Computed tomography of cervical and retropharyngeal lymph nodes: Normal anatomy, variants of normal, and applications in staging head and neck cancer. Part II: Pathology. Radiology 148:715–723, 1983. 44. Maremonti P, Califano L, Longo F, et al: Detection of laterocervical metastases from oral cancer. J Craniomaxillofac Surg 25:149–152, 1997. 45. Miles KA, Lee TY, Goh V, et al: Current status and guidelines for the assessment of tumor vascular support with dynamic contrast-enhanced computed tomography. Eur Radiol 22:1430–1441, 2012. 46. Mokri B, Silbert PL, Schievink WI, et al: Cranial nerve palsy in spontaneous dissection of the extracranial internal carotid artery. Neurology 46:356–359, 1996. 47. Mukherji SK, Castillo M: A simpliied approach to the spaces of the suprahyoid neck. Radiol Clin North Am 36:761–780, v, 1998. 48. Mukherji SK, Kasper ME, Tart RP, et al: Irradiated paragangliomas of the head and neck: CT and MR appearance. AJNR Am J Neuroradiol 15:357–363, 1994. 49. Ng SH, Lin CY, Chan SC, et al: Dynamic contrast-enhanced MR imaging predicts local control in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiotherapy. PLoS ONE 8:e72330, 2013. 50. Okura M, Kagamiuchi H, Tominaga G, et al: Morphological changes of regional lymph node in squamous cell carcinoma of the oral cavity. J Oral Pathol Med 34:214–219, 2005. 51. Parker GD, Harnsberger HR, Smoker WR: The anterior and posterior cervical spaces. Semin Ultrasound CT MR 12:257–273, 1991. 52. Pentenero M, Gandolfo S, Carrozzo M: Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral

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squamous cell carcinoma: A review of the literature. Head Neck 27:1080–1091, 2005. Razek AA, Tawik AM, Elsorogy LG, et al: Perfusion CT of head and neck cancer. Eur J Radiol 83:537–544, 2014. Reede DL, Bergeron RT: Cervical tuberculous adenitis: CT manifestations. Radiology 154:701–704, 1985. Reiseter T, Nordshus T, Borthne A, et al: Lipoblastoma: MRI appearances of a rare paediatric soft tissue tumour. Pediatr Radiol 29:542–545, 1999. Robbins KT: Classiication of neck dissection: Current concepts and future considerations. Otolaryngol Clin North Am 31:639–655, 1998. Rumboldt Z, Al-Okaili R, Deveikis JP: Perfusion CT for head and neck tumors: Pilot study. AJNR Am J Neuroradiol 26:1178–1185, 2005. Sadick M, Sadick H, Hormann K, et al: Diagnostic evaluation of magnetic resonance imaging with turbo inversion recovery sequence in head and neck tumors. Eur Arch Otorhinolaryngol 262:634–639, 2005. Sarvanan K, Bapuraj JR, Sharma SC, et al: Computed tomography and ultrasonographic evaluation of metastatic cervical lymph nodes with surgicoclinicopathologic correlation. J Laryngol Otol 116:194–199, 2002. Shah GV: MR imaging of salivary glands. Neuroimaging Clin N Am 14:777–808, 2004. Shah JP, Strong E, Spiro RH, et al: Surgical grand rounds. Neck dissection: Current status and future possibilities. Clin Bull 11:25–33, 1981. Shingaki S, Takada M, Sasai K, et al: Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas. Am J Surg 185:278–284, 2003. Smith MM: Nonsquamous cell neoplasms of the adult head and neck. Top Magn Reson Imaging 10:304–324, 1999. Som PM: Detection of metastasis in cervical lymph nodes: CT and MR criteria and differential diagnosis. AJR Am J Roentgenol 158:961–969, 1992. Som PM, Curtin HD: Lesions of the parapharyngeal space. Role of MR imaging. Otolaryngol Clin North Am 28:515–542, 1995. Som PM, Curtin HD, Mancuso AA: An imaging-based classiication for the cervical nodes designed as an adjunct to recent clinically based nodal classiications. Arch Otolaryngol Head Neck Surg 125:388–396, 1999. Srinivasan A, Mohan S, Mukherji SK: Biologic imaging of head and neck cancer: the present and the future. AJNR Am J Neuroradiol 33:586–594, 2012.

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68. Sumi M, Izumi M, Yonetsu K, et al: The MR imaging assessment of submandibular gland sialoadenitis secondary to sialolithiasis: Correlation with CT and histopathologic indings. AJNR Am J Neuroradiol 20:1737–1743, 1999. 69. Sumi M, Sakihama N, Sumi T, et al: Discrimination of metastatic cervical lymph nodes with diffusion-weighted MR imaging in patients with head and neck cancer. AJNR Am J Neuroradiol 24:1627–1634, 2003. 70. Sumi M, Van Cauteren M, Nakamura T: MR microimaging of benign and malignant nodes in the neck. AJR Am J Roentgenol 186:749–757, 2006. 71. Tom BM, Rao VM, Guglielmo F: Imaging of the parapharyngeal space: Anatomy and pathology. Crit Rev Diagn Imaging 31:315–356, 1991. 72. Trojanowska A, Trojanowski P, Bisdas S, et al: Squamous cell cancer of hypopharynx and larynx—Evaluation of metastatic nodal disease based on computed tomography perfusion studies. Eur J Radiol 81:1034–1039, 2012. 73. Turkington JR, Paterson A, Sweeney LE, et al: Neck masses in children. Br J Radiol 78:75–85, 2005. 74. van den Berg R, Wasser MN, van Gils AP, et al: Vascularization of head and neck paragangliomas: Comparison of three MR angiographic techniques with digital subtraction angiography. AJNR Am J Neuroradiol 21:162–170, 2000. 75. van den Brekel MW, Castelijns JA: Imaging of lymph nodes in the neck. Semin Roentgenol 35:42–53, 2000. 76. van den Brekel MW, Castelijns JA: What the clinician wants to know: Surgical perspective and ultrasound for lymph node imaging of the neck. Cancer Imaging 5 Spec No A:S41–S49, 2005. 77. Vergeer MR, Doornaert P, Leemans CR, et al: Control of nodal metastases in squamous cell head and neck cancer treated by radiation therapy or chemoradiation. Radiother Oncol 79:39–44, 2006. 78. White JS, Weissfeld JL, Ragin CC, et al: The inluence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol 43:701–712, 2007. 79. Zima A, Carlos R, Gandhi D, et al: Can pretreatment CT perfusion predict response of advanced squamous cell carcinoma of the upper aerodigestive tract treated with induction chemotherapy? AJNR Am J Neuroradiol 28:328–334, 2007.

25 Larynx Hugh D. Curtin

Imaging of the larynx is a challenge.4,12,17,19,27 Motion is a constant problem because breathing and swallowing are very dificult to control, particularly in patients with lesions that impinge on the airway. The patient’s larynx moves slightly with each breath. Despite the dificulties, imaging can still provide important information regarding potential involvement of deeper soft tissues and cartilage. Imaging must be considered in view of the capabilities of modern endoscopy.1,25,31,33 As the technology of imaging has progressed, so too has the instrumentation available for direct visualization. Almost all of the mucosa can be examined very effectively. To be relevant, imaging must provide information that cannot be had by direct visualization. Thus the intent of the radiologist in most cases is to evaluate the deeper tissues. In some cases a bulky lesion of the upper larynx can block the view of the lower larynx, and imaging can assist in deining the caudal extent of disease. Tumors of the lowermost part of the larynx may be dificult to visualize, obscured by the vocal folds. The radiologist must be familiar with the anatomy. The behavior of various disease processes and particularly growth patterns of cancer are extremely important. The radiologist must also be familiar with the available therapeutic options to emphasize the information that will be important in making clinical decisions. There is variability of opinion about some of the more recent surgical strategies, and it is important to work closely with the individual surgeons to ensure that the precise regions of concern are addressed. This chapter begins with a section on anatomy, including the normal appearance in the various imaging planes. A brief discussion of the technical considerations of applying computed tomography (CT) and magnetic resonance imaging (MRI) to the task of examining the larynx is followed by sections on imaging of various pathologic conditions. The important clinical considerations in each disease will be stressed.

ANATOMY The larynx is a system of mucosal folds supported by a cartilaginous framework.12,18 Tension and movement of the mucosal folds is effected by the actions of small muscles pulling against this cartilaginous framework.

Mucosa Clinical descriptions of lesions of the larynx emphasize the mucosal anatomy, so the mucosa is a good starting point for the present discussion. When viewed from superiorly (the view of the endoscopist), the irst landmark seen is the epiglottis (Fig. 25-1). The upper edge of the epiglottis represents the most superior limit of the larynx. The epiglottis is the anterior boundary of the entrance into the larynx. Anteriorly

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two small sulci, the valleculae, separate the free portion of the epiglottis from the base of the tongue (Fig. 25-2). From the lateral margin of the epiglottis, the aryepiglottic (AE) folds curve around to reach the small interarytenoid notch. Together these structures complete the boundaries of the airway at the entrance into the larynx. The inner mucosal surface of the larynx, or endolarynx, can be thought of as the working part of the organ. Two prominent parallel folds stretch from front to back along the lateral aspect of each side of the airway (see Figs. 25-1 and 25-2). These are the true and false vocal cords or folds. They are in the horizontal plane. The true vocal fold (the glottis) is the key functional component in the generation of voice and has a ine edge at the medial margin. The more superiorly placed false vocal fold has a more blunted medial surface. Separating these two folds is one of the most important landmarks in the larynx, the ventricle. The ventricle is a thin cleft between the true and false folds, stretching from the most anterior limit of the fold to a point close to the posterior limit of the larynx. Above the false vocal fold the mucosa sweeps upward and outward to the AE folds. Inferiorly the mucosa covering of the true fold sweeps downward into the subglottic area, eventually merging smoothly with the mucosa of the trachea. A inal important mucosal landmark is the anterior commissure. This is the point where the true vocal folds converge anteriorly to attach to the inner (posterior) surface of the anterior angle of the thyroid cartilage. The three parallel structures—true vocal fold, false vocal fold, and ventricle—organize the larynx into three regions: the supraglottis, the glottis, and the subglottis. The true fold or cord is the glottis. The glottic region of the larynx extends from the upper surface of the true fold to a line somewhat arbitrarily chosen as being 1 cm below the level of the ventricle. The subglottic region is between this arbitrary line and the inferior edge of the cricoid cartilage, the lower margin of the larynx. There is no deined mucosal structure representing the exact boundary or separation of the glottic and subglottic regions. The supraglottic region is the part of the larynx above the ventricle. This region includes the false folds, epiglottis, and AE folds.

Laryngeal Framework The laryngeal cartilages represent the supporting framework of the larynx. The major cartilages include the cricoid, thyroid, arytenoid, and epiglottic cartilages (Fig. 25-3). The smaller cartilages, the corniculate and cuneiform, reside in the AE fold and are not of particular importance to the radiologist. The cricoid cartilage is the foundation of the larynx and is the only complete ring. The posterior part is larger than the anterior, giving the cartilage the appearance of a signet ring facing posteriorly. The upper

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FIG 25-1 Endoscopic view of the larynx using an ofice endoscope. The image is rotated 180 degrees from the usual perspective of the endoscopist. The true vocal fold (1) extends from anterior to posterior and is separated from the false vocal fold (2) by the ventricle (arrowheads). The true folds meet anteriorly at the anterior commissure (small arrow). Larger arrows, aryepiglottic fold. E, epiglottis; P, pyriform sinus. The epiglottis appears fatter than normal because of the perspective.

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FIG 25-2 Larynx split sagittally. View of the lateral wall of the airway. The mucosa over the true vocal fold (1) has been removed to show the thyroarytenoid muscle, which extends from the arytenoid to the thyroid cartilage. The upper edge of the muscle (arrow) indicates the level of the ventricle. The false vocal fold (2) is just above the ventricle. E, epiglottis; F, preepiglottic fat; H, hyoid; T, thyroid cartilage; V, vallecula. (From Curtin HD: The larynx. In Som PM, Bergeron RT, editors: Head and neck imaging, ed 2, St. Louis, 1991, Mosby.)

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FIG 25-3 A, Lateral view of the cartilaginous skeleton. The thyroid cartilage is the largest of the cartilages and articulates with the cricoid cartilage (C) posteriorly and inferiorly. The epiglottis is partially hidden as it disappears behind the thyroid cartilage. H, hyoid bone. B, The thyroid cartilage is now partially transparent, showing the lower extension of the epiglottis (petiole). The small arytenoid cartilage is seen perched on the cricoid cartilage posteriorly. (From Curtin HD: The larynx. In Som PM, Curtin HD, editors: Head and neck imaging, ed 4, St. Louis, 2003, Mosby.)

margin of the cricoid slopes inferiorly toward the anterior midline. The upper margin of the larger posterior part of the cricoid cartilage reaches the level of the cricoarytenoid joint and the true vocal fold. The lower margin of the cricoid cartilage represents the lower margin of the larynx. The thyroid and arytenoid cartilages articulate with the cricoid cartilage. The thyroid cartilage is large and can be thought of as forming a shield for most of the inner larynx. The arytenoid cartilages perch on the superior edge of the posterior cricoid cartilage. The arytenoid cartilage is situated in the posterior larynx and vertically crosses the level of the ventricle. The vocal process at the level of the true vocal fold projects anteriorly from the lowermost part of the arytenoid cartilage. Because of its characteristic shape and position, the arytenoid cartilage can help localize the ventricle on axial scanning. This is most helpful with CT, because the vocal process may be directly visualized. The upper margin of the arytenoid is at the level of the lower false fold just above the ventricle. The vocal process is at the level of the true fold just below the ventricle. Indeed, the vocal ligament, which represents the medial margin of the true vocal fold, attaches to the vocal process. The epiglottic cartilage, with the exception of its superior tip, is contained within the external framework of the larynx. This cartilage is made of elastic ibrocartilage and does not ossify. Grossly this cartilage has multiple perforations resembling more a mesh than a solid plate, so the epiglottic cartilage is not a major barrier to tumor spread. Inferiorly the epiglottic cartilage is connected to the inner surface of the anterior part of the thyroid cartilage by the thyroepiglottic ligament.

Muscles and Ligaments The cartilages are connected by a system of muscles and ligaments. Several muscles are mentioned in the remainder of the chapter; one

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M

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tions of the paraglottic space vary, this discussion will use Tucker’s original descriptions, with the medial boundary represented by the conus elasticus and quadrangular membrane.32 The lateral boundary is the external skeleton of the larynx, predominantly formed by the inner cortex of the thyroid cartilage. At the level of the supraglottic larynx, the paraglottic space is predominantly illed with fat. Below the ventricle the TAM ills the paraglottic region. A small recess of the ventricle extends upward into the paraglottic space of the supraglottic larynx. This is called the laryngeal saccule or appendix. This structure is within the paraglottic fat lateral to the quadrangular membrane. The preepiglottic space is between the epiglottis posteriorly and the thyroid cartilage and thyrohyoid membrane anteriorly. The hyoepiglottic ligament forms the roof of the preepiglottic and paraglottic spaces.

IMAGING CONSIDERATIONS C

FIG 25-4 View from above, looking down at the skeletonized larynx. The thyroarytenoid muscle (M) is seen stretching from the arytenoid (A) to the thyroid cartilage. C, cricoid. The arrow indicates the point where paraglottic spread of tumor is expected to intersect the lateral vocal fold. The opposite side shows the vocal ligament stretching from the vocal process of arytenoid to the thyroid cartilage. (From Curtin HD: MR and CT of the larynx. In Thrall JH, editor: Current practice of radiology, ed 3, St. Louis, 1994, Mosby.)

deserves special attention in a discussion of larynx imaging. The thyroarytenoid muscle (TAM) stretches from the arytenoid cartilage to the inner surface of the anterior thyroid cartilage (Fig. 25-4; see Fig. 25-2). This muscle parallels the true fold and makes up the bulk of the true vocal fold. The characteristic shape of this muscle allows identiication of the true vocal fold level at imaging. The cricothyroid and thyrohyoid membranes span the greater part of the intervals between the cricoid cartilage, thyroid cartilage, and hyoid bone and represent, along with the cartilages, the outer limits of the larynx. Notably the cricothyroid membrane is considered to be incomplete lateral to the anterior midline. Two membranes are found just deep to the mucosa. The conus elasticus (also called the cricovocal ligament or lateral cricothyroid ligament) stretches from the vocal ligament to the upper margin of the cricoid cartilage. Some descriptions include the membrane attaching to the inner surface of the ring as well. This membrane or fascial layer merges with the anterior cricothyroid ligament in the anterior midline. A similar structure is seen in the supraglottic larynx. A thin ligament called the ventricular ligament is found in the lower margin of the false fold, and the quadrangular membrane sweeps superiorly from the ventricular ligament and terminates in the AE fold. The fan-shaped hyoepiglottic ligament stretches from the epiglottis to the hyoid and divides the supraglottic larynx into a superior (suprahyoepiglottic) area and an inferior (infrahyoepiglottic) area.36

The radiologist can use either CT or MRI to image the larynx. MRI has a theoretical advantage in differentiating soft tissues, but CT has a deinite advantage in speed. Radiologists at this institution begin with CT and occasionally do limited MRI to clarify a speciic issue. Multidetector CT can cover the entire larynx in just a few seconds. The thin slice thickness allows multiplanar reformatted images comparable in quality to direct imaging (see Fig. 25-6). Because the scan can be done so quickly, the contrast can be ideally planned for best visualization of the anatomy and the pathology. MRI can separate or distinguish various soft tissues slightly better than CT. This may allow better analysis of potential cartilage invasion and has been considered to have an advantage in deining the tumor-muscle interface. Motion artifact is a signiicant problem when imaging the larynx. CT scanning avoids the problem by using fast imaging. The multidetector acquisition covers the larynx in a few seconds. The examination can be performed during slow shallow respiration, or the scan can be done with the breath held. More elaborate schemes are required for MRI studies. At this institution the patient practices breathing with the abdominal muscles rather than the chest muscles. This is done before the examination begins, usually before the patient is put on the examination table. Specialized neck coils or surface coils are positioned so that any chest movement does not bump the coil. Although speed of imaging is always an advantage, some have recommended using multiple excitations on the T1-weighted sequence. This gives longer imaging times but averages out some of the motion. At this institution, contrast material is usually used when imaging tumor cases. Gadolinium combined with fat suppression can emphasize tumor margins. Fat suppression with the T2-weighted images can help in the evaluation of cartilage involvement. Imaging emphasizes the importance of the ventricle. Axial images are taken along the plane of the ventricle. The position of the ventricle is estimated in axial images by the appearance of the cartilages or by the transition from fat to muscle in the paraglottic region. The coronal images are perpendicular to the ventricle. Even if the ventricle is not actually seen, its position can be predicted by the transition from fat to muscle in the paraglottic space.

Spaces

PATHOLOGY

The paraglottic space and the preepiglottic space are found between the mucosal surface and the cartilaginous outer limit of the larynx. The paraglottic space is found laterally and represents much of the soft tissue wall of the larynx (Figs. 25-5 and 25-6). Although descrip-

Most laryngeal imaging is done for evaluation of tumors or for assessment of patients with trauma to the larynx.4,11,12,17,19 The tumors can be subdivided into mucosal and submucosal groups. In most instances the larynx is directly visualized—if not by endoscopy, at least by

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E FIG 25-5 Axial contrast-enhanced CT scan through the larynx from superior to inferior. A, Supraglottic larynx (level of upper thyroid cartilage); most of the wall of the larynx is fat density. C, carotid artery; E, epiglottis; J, jugular vein; PES, preepiglottic space. B, Supraglottic larynx inferior to A. The paraglottic space (arrow) is illed with fat density. Arrowhead represents the aryepiglottic fold. SCM, sternocleidomastoid muscle; T, thyroid cartilage. C, Just above the ventricle (level of the false vocal fold) the paraglottic space is illed with fat (arrow). The upper arytenoid cartilage (A) is visible. D, At the true vocal fold level, the thyroarytenoid muscle (TAM) ills the paraglottic space. Arrowhead represents the cricoarytenoid joint. The upper margin of the cricoid cartilage is visible. E, At the subglottis, the mucosa is tightly applied to the inner surface of the cricoid ring (C) without intervening soft tissue.

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moderate-sized tumors, in whom some type of voice-sparing therapy is considered. Such treatment options include partial laryngectomies, radiotherapy, or organ-sparing strategies that include radiation and chemotherapy as an initial approach. The feasibility of these therapies depends on the origin and extent of the tumor. In very extensive tumors where total laryngectomy is likely, imaging gives a baseline evaluation and helps evaluate the lymph nodes. Ultrasound has been useful in evaluating lymph nodes, and many institutions perform positron emission tomography (PET)/CT to evaluate nodes and possible distant metastases. PET/CT will also ind occasional second primaries. The precise information required by the various clinicians varies. Perhaps the most precise anatomic analysis is targeted at the feasibility of doing a surgical partial laryngectomy. Originally these voice-sparing partial laryngectomies were performed through open neck approaches. Now more partial resections are done via endoscope using lasers. Many patients who would have been candidates for open partial laryngectomies are now treated with various chemoradiation (chemoRT) organpreserving protocols. Even though open partial laryngectomies are done much less common than previously, we still use the landmarks described for these techniques in our evaluation of larynx cancers. This approach with very slight modiications provides the information required by any of the therapeutic strategies considered. The discussion of imaging of carcinoma of the larynx is organized based on the site of origin of the tumor.

Supraglottic Tumors. The classic voice-sparing surgical option for T

B FIG 25-6 Coronal reformat through the larynx (multidetector CT). A, Quiet respiration. The thyroarytenoid muscle (TAM) is seen in cross section with a triangular shape. This muscle represents the bulk of the true vocal fold. The level of the ventricle (arrowhead) is predicted as the transition between the muscle density of the true fold and fat density of the paraglottic space (arrow) at the supraglottic level. C, cricoid cartilage; T, thyroid cartilage. The lower half of the thyroid cartilage is heavily ossiied; the upper half is nonossiied, giving the difference of density. B, The patient is holding his breath. The position of the closed airway is represented by the dashed line. Note the density of fat in the paraglottic space at the supraglottic level (arrow). The TAM (arrowhead) forms the bulk of the true vocal fold (glottic level). H, hyoid bone; T, thyroid gland. The thyroid cartilage and cricoid cartilage are also visible.

mirror—and the radiologist should pursue information that is not obtainable by direct visualization.

Mucosal Tumors Most tumors evaluated by imaging are squamous cell carcinomas arising from the mucosa of the larynx.3,28 With the possible exception of extremely rare lesions arising deep within the ventricle, these tumors are almost always detected before imaging. Indeed, imaging cannot currently rule out a small malignancy and so is not a substitute for direct visualization. The otolaryngologist can completely assess smaller lesions. The margins of a small tumor may be readily visible and no further information is required. Imaging is important for patients with

supraglottic squamous cell carcinoma is the supraglottic laryngectomy22,31 (Fig. 25-7). The resection is made along the ventricle, and the entire supraglottic larynx is removed, leaving at least one and usually both arytenoid cartilages. The patient retains the true folds and so generates voice in the usual manner with the normal neuromuscular mechanisms. The protective function of the supraglottic larynx, particularly the epiglottis, is lost, and the patient must learn to swallow without aspirating. The classic open surgical partial laryngectomy is done via open skin incisions, but currently larynx surgeons perform these partial resections endoscopically using lasers.31 The anatomic landmarks emphasizing the ventricle are the same for both approaches. Tumor crossing the ventricle is the primary contraindication for the standard supraglottic laryngectomy (Box 25-1). The incision passing along the ventricle would cut through tumor. Tumor growing along the mucosa to reach the true vocal fold may be obvious at direct visualization. Tumors may invade into the deeper tissues laterally and follow the paraglottic space around the ventricle into the lateral edge of the true vocal fold. This type of spread is unusual as an isolated phenomenon but should be checked when imaging a supraglottic tumor. Axial imaging parallels the ventricle and therefore is somewhat limited in precisely identifying the level of this key structure. The paraglottic space at the false vocal fold level is predominantly fat, but at the true vocal fold level is predominantly muscle. The transition between the two represents the approximate level of the ventricle. If a normal slice can be found below the tumor but still within the supraglottic larynx, the supraglottic laryngectomy is technically possible (Fig. 25-8). If the tumor can be identiied at the level of the vocal fold as well as in the supraglottis, the patient cannot have the standard supraglottic resection (Fig. 25-9). If surgery is chosen as the therapy, the usual procedure would be a total laryngectomy although some more extensive procedures have been described, taking larger parts of the larynx (see later). As endoscopic resections advance, new strategies can extend the ability to take tumors at lower levels. Describing the most inferior extent of the tumor relative to the ventricle is very

CHAPTER 25

E

A E

2

T

C

FIG 25-7 Diagram of a supraglottic laryngectomy. Dotted line shows the incision of a supraglottic laryngectomy, passing along the ventricle between the true vocal fold and the false vocal fold (2). AE, aryepiglottic fold; C, cricoid cartilage; E, epiglottis; T, thyroid cartilage. (From Curtin HD: Imaging of the larynx: Current concepts. Radiology 173: 1–11, 1989.)

Contraindications to Classic Supraglottic Laryngectomy BOX 25-1 • • • • • • •

Tumor extension onto the cricoid cartilage Bilateral arytenoid involvement Arytenoid ixation Extension onto the glottis or impaired vocal cord mobility Thyroid cartilage invasion Involvement of the apex of the piriform sinus or postcricoid region Involvement of the base of the tongue more than 1 cm posteriorly to the circumvallate papillae

From Lawson W, et al: Cancer of the larynx. In Suen JY, Myers E, editors: Cancer of the head and neck, New York, 1989, Churchill Livingstone, pp 533–591.

important in such cases. Alternatively these patients may be considered for organ-sparing chemoRT protocols. On axial images, the lateral edge of the TAM should be carefully examined for the earliest evidence of transglottic (from false fold to true fold) spread. A narrow extension of the paraglottic fat is often seen along the outer (lateral) margin of the muscle (see Fig. 25-9). Tumor spreading around the ventricle will grow into this fat and eventually appear to “pry” the muscle away from the thyroid cartilage. Coronal images are perpendicular to the ventricle and may also be helpful in

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showing the relationship between tumor and the lateral aspect of the true vocal fold. Tumor can be distinguished readily from the fat in the supraglottic paraglottic space. The interface between tumor and muscle at the true fold level is more dificult to visualize. MRI studies have the advantage of better tissue differentiation using various pulse sequences, but this advantage can be realized only if the patient is able to control motion (Fig. 25-10). In our experience the ability to optimize the contrast injection with CT scanning may allow good differentiation of the tumor from muscle, diminishing the soft tissue advantage of MRI. Midline tumor can cross the level of the ventricle to involve the anterior commissure. This area can be dificult to evaluate either by direct visualization or by imaging. If there is deep growth from the anterior commissure into the attachment of the cord or through the cricothyroid membrane, imaging may detect tumor that is unappreciated clinically. Anterior growth from a supraglottic carcinoma brings the tumor into the preepiglottic space (see Figs. 25-9 and 25-10). The preepiglottic space and paraglottic space have a rich lymphatic drainage, and tumor invasion heightens the concern regarding nodal metastases. Invasion is easily appreciated on axial imaging because the tumor is contrasted against the fat. Such involvement is not a contraindication to a supraglottic laryngectomy. Thyroid cartilage invasion is usually considered a contraindication to the supraglottic laryngectomy. Such invasion is extremely uncommon unless the tumor is large and has crossed the ventricle.20 In such a case the patient would be excluded as a candidate on the basis of ventricular involvement. Involvement of the epiglottic cartilage is not a contraindication. Cartilage assessment is discussed under the heading “True Vocal Fold Tumors.” The supraglottic partial laryngectomy is the classic surgical therapy for tumors limited to the area above the ventricle. More extensive resections have been used for lesions extending beyond the boundaries of supraglottic laryngectomy.31 Pearson’s near-total laryngectomy can be done for supraglottic cancer extending to one vocal fold. The resection is continued to include the vocal fold and take the upper margin of the cricoid. The supracricoid partial laryngectomy with cricohyoidopexy takes the anterior vocal folds to the level of cricoid. Minor involvement of the thyroid cartilage is not a contraindication. In either of these approaches the inferior extent remains the most important assessment at imaging. As stated previously, the modern alternative to partial laryngectomy is endoscopic laser surgery.31 Lesions of the suprahyoid epiglottis, AE fold, and false vocal folds are more appropriate for this type of surgery than are lesions of the laryngeal surface of the epiglottis. The latter tumors are partially hidden by the epiglottis and thus less accessible to endoscopic resection. Radiation therapy and chemoRT protocols are also performed for supraglottic cancer. The same landmarks and considerations for supraglottic laryngectomy pertain to assessment for these therapeutic options. The bulk of the tumor is also a prognostic factor. Larger tumors do worse than smaller. One study used a 6-mL volume as a separation, with larger tumors showing signiicantly worse prognosis than smaller ones.26 Nodal metastases are very frequent in supraglottic tumors and can be bilateral.

True Vocal Fold Tumors. There are several options for therapy of relatively small glottic carcinomas.31 These include simple resection, endoscopic laser resection, and radiotherapy. The classic vertical hemilaryngectomy may be considered for a more extensive lesion at the level

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D FIG 25-8 Supraglottic carcinoma not reaching the level of the ventricle or true fold. A, Axial plane. Tumor (T) of supraglottis/aryepiglottic fold. N, metastatic node. B, Axial plane, inferior to A. The paraglottic fat (arrow) is normal at this level, situated between tumor and the level of the ventricle. C, True vocal fold level is normal. D, Coronal. The inferior margin (arrow) of the tumor separable from the level of the ventricle and upper margin of the true vocal fold (arrowhead).

of the true vocal fold. This procedure removes the true and false vocal folds on one side of the larynx using a vertical incision through the thyroid cartilage. The lesion can cross the anterior commissure and involve the anterior one third of the opposite vocal fold and still be treatable by vertical hemilaryngectomy. The incision through the thyroid cartilage is moved laterally toward the opposite side. At our institution, most resections of glottic-level tumors are performed endoscopically using a standard cutting laser or the KTP (potassium titanylphosphate) angiolytic laser to interrupt the blood supply to a part of the tumor.2,35 No matter the preferred approach, evaluating the lesion as though the patient is a candidate for open classic vertical hemilaryngectomy will emphasize the important surgical landmarks. Various strategies to extend some of the limits have been developing rapidly in the laryngeal surgical community. The contraindications for the classic vertical hemilaryngectomy are listed in Box 25-2.22 The most important assessments done at imaging involve the inferior extension of the tumor, deep invasion at the anterior commissure, and cartilage invasion. Submucosal superior extension crossing the ventricle into the supraglottic larynx is only an occasional problem. The proximity of tumor to the cricoarytenoid joint should be deined. Deep posterior paraglottic extension along the lateral aspect of the vocal process has been described as being particularly important in endoscopic resections.27 Inferior extension is quantiied relative to the upper margin of the cricoid cartilage. The cricoid cartilage is the foundation of the larynx,

Contraindications to Vertical Frontolateral Hemilaryngectomy* BOX 25-2

• Tumor extension from the ipsilateral vocal cord across the anterior commissure to involve more than one third of the contralateral vocal cord • Extension subglottically >10 mm anteriorly and >5 mm posterolaterally • Extension across the ventricle to the false cord • Thyroid cartilage invasion • Impaired vocal cord mobility a relative contraindication From Lawson W, et al: Cancer of the larynx. In Suen JY, Myers E, editors: Cancer of the head and neck, New York, 1989, Churchill Livingstone, pp 533–591. *This technique can still be used if the vocal process and anterior surface of the arytenoid are involved, but involvement of the cricoarytenoid joint, interarytenoid area, opposite arytenoid, or rostrum of the cricoid is a contraindication.

and classically only very limited partial resections or cortical shavings have been possible. Recently some surgeons have devised strategies to resect segments of the cricoid and reconstruct a scaffold to support the airway. For instance, an aortic graft has been strong enough to replace a section of this important cartilage.37

CHAPTER 25

Larynx

T T

SCM

B

A

T

D

C

C

T

E

C

F FIG 25-9 Postcontrast CT scan shows transglottic tumor. The lesion appeared to arise from the supraglottic larynx. A, Axial image through the level of the supraglottis. The tumor (T) ills much of the paraglottic space at the level of the supraglottis. Note the normal fat (arrow) in the opposite paraglottic space. Arrowhead indicates thyroid cartilage. B, Axial image slightly inferior to A. Tumor (T) continues inferiorly. Note the airilled laryngeal appendix (arrow) in the paraglottic fat on the normal side. SCM, sternocleidomastoid muscle. C, Axial image level of the ventricle/upper true vocal fold. Tumor (T) ills the right side. On the left there is a small amount of normal fat (arrow) just lateral to the thyroarytenoid muscle (TAM). The cricoarytenoid joint (arrowhead) is also an indicator that the scan is entering the true vocal fold level. D, Axial image of true vocal fold level. The tumor distorts the true fold on the right. The normal TAM (arrowheads) indicates the level of the true vocal fold. A small amount of residual normal paraglottic fat (arrow) reaches this level. E, Axial image at the level of the upper subglottis. The tumor (arrowhead) is seen along the inner cortex of the cricoid cartilage (C). F, Coronal reformatted image. The tumor (T) ills the supraglottis on the right and iniltrates the true vocal fold (arrow), massively increasing its size. The tumor touches the cricoid (C) in the subglottis. The approximate level of the ventricle on the left is indicated by the dashed line. A small invagination of paraglottic fat (arrowhead) is demonstrated at the upper outer margin of the TAM at the true vocal fold level on the normal side.

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T

A

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T

V TAM

C

D FIG 25-10 Supraglottic tumor. A, Axial T1-weighted image. The tumor (T) ills most of the right supraglottic larynx and crosses the midline. Paraglottic and preepiglottic spaces are invaded. Note that the tumor and the prelaryngeal strap muscles (arrow) have the same signal intensity. The strap muscle would have the same signal as the thyroarytenoid muscle (TAM). B, Axial T2-weighed image. The tumor has signiicantly more signal than the prelaryngeal strap muscle. Arrowhead indicates fat in the medullary cavity of the ossiied thyroid cartilage. C, Axial T2-weighted image at the level of the true vocal fold. The TAM (arrow) is normal with approximately the same signal as the strap muscles. The tumor has not reached this level. D, Coronal postcontrast T1-weighted image. The tumor (T) ills the supraglottis but is separated from the TAM and thus the true fold by a small amount of fat (arrow) in the paraglottic space at the level of the ventricle (V).

At imaging, if the tumor can be identiied within the ring of the cricoid cartilage, the classic open vertical laryngectomy cannot be done (Fig. 25-11). Deep invasion at the anterior commissure and anterior midline can involve the thyroid cartilage or the cricothyroid membrane (Figs. 25-12 and 25-13). The subtle fat plane just external to the membrane should be examined closely on the axial image. Cartilage invasion is considered a contraindication for vertical hemilaryngectomy and is very important in radiation or chemoRT protocols. Minor thyroid cartilage invasion has been treated with supracricoid partial laryngectomy with cricohyoepiglottopexy. This procedure removes more of the supraglottic larynx, thus suspending the cricoid cartilage from the remaining supraglottic tissues and hyoid. If the tumor reaches the cricoid, a segment of the cricoid can still be

removed if there is an appropriate strategy to reconstruct (e.g., placement of a segment of cadaver aortic graft).37

Cartilage Invasion. Cartilage invasion is considered a contraindication to both the standard supraglottic and vertical hemilaryngectomies. Assessment of the cartilage is important for radiation planning or for inclusion in various chemoRT strategies. The subject is discussed here because such invasion is of more concern in lesions involving the true vocal fold. With both CT and MRI studies, the most reliable sign of cartilage involvement is identiication of tumor on the extralaryngeal or outer surface of the cartilage. Minor degrees of cartilage invasion can be dificult to detect. The variability of ossiication of the major cartilages can lead to problems detecting cartilage invasion.

CHAPTER 25 The nonossiied part of the cartilage can have approximately the same appearance as tumor on CT scans. MRI studies have an advantage of better tissue discrimination, and although there are no large series available, limited results suggest that tumor can be differentiated from nonossiied cartilage based on signal.9,10 If there is bright signal on the T1-weighted image, that part of the cartilage can be reliably considered normal (Fig. 25-14). The high signal represents fat in

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ossiied cartilage; carcinoma is never that bright. On T1-weighted images, tumor and nonossiied cartilage are usually intermediate or dark. The nonossiied cartilage may be slightly darker than tumor. Regions that are dark on T1-weighted images are examined on the long-TR (repetition time) sequence. Nonossiied cartilage remains relatively dark on long-TR sequence images. Tumor tends to be signiicantly brighter than nonossiied cartilage (see Fig. 25-14). We prefer fat suppression on T2-weighted sequences so that all normal cartilage is dark and abnormal cartilage is of higher signal. Nonossiied cartilage does not enhance with gadolinium, whereas tumor invading cartilage does enhance to some extent. Again, we prefer to use fat suppression on the T1 sequences taken after gadolinium. Tumor, then, is dark or intermediate on T1-weighted images and is usually relatively brighter on T2-weighted images and enhances after gadolinium. This signal pattern does not deinitely mean tumor. Edema, ibrosis, and even red marrow have been described with this pattern.6,8 Edema is of particular concern because squamous cell carcinoma often has a peritumoral inlammatory response. Edema may be brighter than tumor on T2-weighted imaging, but more experience

A

N

FIG 25-12 Tumor of the anterior commissure extending anteriorly. A

B FIG 25-11 Tumor of vocal fold with subglottic extension. Axial CT with contrast. A, Tumor (arrow) at level of true vocal fold. B, Subglottic extension shows tumor (arrow) along the inner cortex of cricoid inferior to the level of the upper margin.

small tumor was seen at the anterior commissure (white arrow). Anterior extension carried the tumor through the thyroid cartilage (arrowheads), with a prominent nodule in the anterior soft tissues (black arrow). N, metastatic node. (From Curtin HD: The larynx. In Som PM, Bergeron RT, editors: Head and neck imaging, ed 2, St. Louis, 1991, Mosby.)

T

c

A

B

FIG 25-13 Cancer of true vocal fold/ventricle extending via paraglottic space through cricothyroid interval. A, Coronal postcontrast CT image shows tumor (T) centered on the ventricle, illing the paraglottic space. The tumor extends inferiorly to reach the cricoid cartilage (C). B, Axial image shows tumor (arrow) extending into fat anterior to the cricothyroid membrane (interval). Compare to normal fat on opposite side.

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OC

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A Post Gad FS

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NOC

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E T OC

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T2 FS T

T

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F FIG 25-14 Squamous cell cancer invading lower thyroid cartilage. A-C, Normal noninvaded cartilage. A, Axial T1-weighted MRI shows high signal of fat in ossiied cartilage (OC). Nonossiied cartilage (NOC) shows low signal similar to the tumor (T). B, Both OC and NOC have low signal on fat-suppressed T2-weighted MRI. C, With postcontrast fat suppression, neither OC nor NOC enhance. D-F, Direct invasion anteriorly (T) and inlammatory edema (E) posteriorly. D, Axial T1-weighted MRI shows the tumor (T) invading the cartilage; invading tumor has approximately the same signal as the main bulk of the tumor. More posteriorly, inlammatory edema (E) has similar signal pattern as the tumor. E, Fat-suppressed T2-weighted MRI shows intermediate signal of the invading tumor (T) similar to the bulk of the tumor, but the more posterior cartilage shows inlammatory edema (E) with signiicantly higher signal than that of the tumor. F, Postcontrast fatsuppressed T1-weighted axial image shows enhancement of the invading tumor (T) similar to the bulk of the tumor. More intense enhancement is present in the segment with inlammatory edema (E).

CHAPTER 25 is needed before a deinite statement can be made regarding making this differentiation. Edema of the cartilage presumably means that tumor is at least very close. In our experience, at least the perichondrium has been invaded if there is “edema” (high T2 signal) in the cartilage. A CT irregularity of the inner cortex may suggest that tumor is eroding, but this sign is questionable owing to the variability of ossiication.13 The cortex may be interrupted normally. Asymmetric sclerosis, particularly of the thyroid and cricoid cartilages, may indicate tumor.7 The normal arytenoid cartilage can ossify asymmetrically, so sclerosis is not as good an indicator of tumor.34 Tumor may obliterate the medullary fat within the cartilage. Very recently dual-energy CT has been suggested as an approach to evaluating possible invasion of cartilage.15,21 Tumor tends to invade ossiied cartilage rather than nonossiied cartilage.20 Invasion of ossiied cartilage shows loss of bone density and loss of medullary fat density. An intact bone density cortex of ossiied cartilage is considered evidence that tumor has not invaded. However, nonossiied cartilage can have the same density as tumor; both are relatively dense compared to muscle. The problem becomes distinguishing the density of enhancing tumor from the relatively high density of nonossiied cartilage. Nonossiied cartilage can mimic tumor invading and destroying ossiied cartilage. By scanning with two different energies, one may be able to make the differentiation. Because of the presence of the iodine peak, density due to iodine can be separated from density due to protein or other substances that, although dense, do not contain signiicant iodine. Nonossiied cartilage does not have a signiicant blood supply and thus does not show a prominent iodine-based enhancement. Further study regarding the signiicance of various signal patterns and CT indings is needed. For instance, the effect of various imaging indings on the prognosis of various therapies, particularly radiotherapy, could potentially change management.10,23,24

Subglottic Tumors. Subglottic tumors are rare. When they do occur the only surgical option usually is a total laryngectomy because of the proximity to the cricoid cartilage. Because the cricoid is such an important landmark for both areas, glottic and subglottic tumors are often considered together in imaging strategies. This allows separation of lesions into two groups: supraglottic and glottic/subglottic.

Hypopharyngeal Tumors. The hypopharynx is not actually part of the larynx but is so intimately associated that discussion is warranted in this chapter. Decisions about potential surgical resection usually relate to the proximity of the tumor to landmarks within the larynx, so the assessment is similar to that of lesions within the larynx itself. Two regions of the hypopharynx have important relationships to the larynx: the pyriform sinuses and the postcricoid region. The pyriform sinuses indent the posterior wall of the larynx. The anterior wall of the pyriform sinuses represents the posterior wall of the paraglottic space. The pyriform sinus makes up the lateral aspect of the AE fold. If a tumor is localized to the upper pyriform, a supraglottic resection may be considered along with resection of the tumor. A tumor that invades the paraglottic region of the larynx can follow the paraglottic pathway to reach the level of the true vocal fold (Fig. 25-15). The postcricoid region is that area of the lower hypopharynx that covers the posterior aspect of the cricoid cartilage. To achieve an appropriate margin the cricoid must usually be removed, and thus a total laryngectomy is most commonly performed or organ preservation strategies considered. In these patients the inferior extension within the pharynx should be estimated to help the surgeon decide the appropriate method of reconstructing the food passage. The key landmark

C

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T

FIG 25-15 Tumor (T) of the pyriform sinus. The lesion protrudes through the thyroarytenoid gap between thyroid cartilage and arytenoid (arrow). The tumor thus invades the paraglottic space (arrowhead) of the supraglottic larynx. Compare with the fat in the paraglottic space on the normal side. C, carotid artery.

is the transition from the oval appearance of the pharyngeal musculature to the round appearance of the esophageal musculature as appreciated in the axial plane (Fig. 25-16). This transition is closely approximated by the lower margin of the cricoid cartilage.

Lymph Node Metastases. Metastasis to the lymph nodes is a major consideration in carcinoma of the larynx. The subject of lymph nodes is discussed in Chapter 24, but brief comments about major pathways of spread are appropriate. Nodal metastases are a major concern with supraglottic tumors. Spread to the jugular nodes is very frequent because of the rich lymphatic drainage. The margin of the true vocal fold does not have any lymphatics. Therefore tumors of the true vocal fold do not spread to the lymph nodes unless there is deep invasion or, alternatively, the tumor has grown along the mucosa to involve the subglottic region. The subglottic mucosa does have lymphatic drainage, so a primary tumor arising in this location or a glottic tumor extending into the area secondarily can metastasize to the nodes. In these patients the nodes along the esophagus and in the upper mediastinum become a signiicant concern.

Radiation Therapy and Chemoradiation for Mucosal Tumors. The evaluation of patients from a surgical perspective uses landmarks that are slightly more precise, but many of the same indings are appropriate for those patients for whom radiotherapy or chemoRT is chosen as the treatment. The dimensions of the tumor are relevant in that this relects the bulk of the tumor and relates to the depth of invasion into the soft tissues. The volume of the tumor has been used to suggest prognosis after treatment with radiation therapy.26 The vertical extent should be estimated, although the precision relating to the ventricle is less crucial. Extension into the subglottic area is very important because the treatment portals may be changed to include the paratracheal and upper mediastinum regions. Formerly, cartilage involvement was considered a contraindication to radiation therapy. Cartilage invasion makes tumor recurrence more

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A

T J C

B FIG 25-16 Axial CT scan showing transition from pharynx to esophagus. A, Axial image through the inferior pharynx. The pharynx has an oval appearance (arrowheads) stretching from side to side. This is approximately at the level of the cricopharyngeus where the muscles attach to the more lateral cricoid cartilage. Arrow indicates cricoid cartilage. B, Level of the esophagus. The esophagus is seen as a round structure (arrow). C, carotid artery; J, jugular vein; T, thyroid gland.

frequent, as is radiation chondritis and chondronecrosis. Recently, however, some have expressed the opinion that relatively subtle involvement is not an absolute contraindication.

Other Mucosal Tumors. Many benign lesions such as polyps and papillomas arise from the mucosa of the larynx. These are seldom evaluated by CT or MRI studies. Submucosal tumors can ulcerate through the mucosa (see “Submucosal Tumors”). Although almost all malignancies arising from the mucosa of the larynx are squamous cell carcinoma, occasional malignancies arise from the minor salivary glands, with histologies such as adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma. Verrucous carcinoma is an exophytic slow-growing variant of squamous cell carcinoma. Usually it does not metastasize but can be locally aggressive. There are no particular imaging features, but the lesion has a typical exophytic “warty” appearance at direct inspection.

Submucosal Tumors Lesions presenting beneath an intact mucosa usually arise from the nonepithelial elements of the larynx.3,5,12,14,28 Such tumors include chondroid lesions, hemangiomas, vascular malformations, neurogenic tumors, and rare lesions such as leiomyoma, rhabdomyoma, and lipomas. Sarcomas arising from the same various mesenchymal

elements are often submucosal but with increasing size can lead to mucosal ulceration. Rarely a squamous cell carcinoma can appear to be entirely submucosal. Such a lesion arises in the ventricle or ventricular saccule (appendix). The tumor expands upward into the paraglottic space and downward into the true vocal fold rather than medially toward the lumen of the larynx. A submucosal tumor represents a different problem than the mucosal lesion. Unlike the squamous cell carcinoma, where the actual tumor can be seen and easily biopsied, the submucosal tumor presents as a bulge beneath an intact mucosa. In these patients, imaging is used not only to show the extent of the lesion but also to help identify the type of tumor. In certain tumors, the indings are characteristic enough that the diagnosis can be made accurately. In patients in whom the diagnosis is not deinite after imaging, certain indings can still be helpful to the otolaryngologist. The irst question is whether the tumor is a chondroid lesion. Chondrosarcomas and chondromas arise from the cartilaginous framework of the larynx16,30 (Figs. 25-17 and 25-18). Most arise from the cricoid. The thyroid cartilage is the second most common site of origin. Differentiation between benign and malignant can be impossible even at histopathologic examination. Most are considered to be low-grade chondrosarcomas. These tumors can compromise the airway, and treatment is usually surgical. A partial laryngectomy can be curative if the entire lesion is resected. If the cricoid cartilage is signiicantly involved, a total laryngectomy may be considered because of the key role of this cartilage in maintaining a patent airway. Many surgeons will consider partial resection with debulking the lesion, leaving the smallest amount of tumor possible. Close imaging surveillance is mandatory with this approach. If partial resection is planned, the relationship of the tumor to the cricoarytenoid joint is extremely important. On either CT scan or MRI study, the cartilage origin may be obvious and give a clue to the identity of the lesion (see Fig. 25-17). The cartilage may be expanded, indicating a lesion arising within rather than eroding into the cartilage from a more supericial mucosal origin. The cartilaginous matrix is the most characteristic inding at imaging (see Fig. 25-18). CT scans are better than MRI studies at demonstrating the calciications within the matrix of the tumor. Such calciications are extremely rare in other lesions. Relapsing polychondritis can give fairly extensive calciication but is extremely rare and should not involve the larynx exclusively. If the lesion does not have the imaging characteristics of a cartilage lesion, the radiologist tries to determine whether the lesion is vascular. Hemangiomas, venous vascular malformations, and paragangliomas enhance intensely on CT scans if a bolus or rapid drip of intravenous contrast material is used. Knowledge that a tumor is vascular has obvious implications if biopsy or resection is planned. Other than chondrosarcomas and vascular lesions, soft tissue tumors do not have speciic identifying characteristics. They do not have a cartilaginous matrix and do not enhance brightly. The absence of these two imaging characteristics is useful information in limiting the diagnostic possibilities.

Cysts Cysts also present as submucosal masses. Three types of cysts typically arise within or in intimate association with the larynx. The saccular cyst (laryngocele) and the mucosal cyst arise within the larynx. The thyroglossal duct cyst arises just outside the larynx in close association with the strap muscles. The saccular cyst (laryngocele) represents a dilatation of the ventricular saccule or appendix (Fig. 25-19). Strict terminology refers to

CHAPTER 25

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A C

C

B

A

V

C

C

C

D FIG 25-17 Chondroid lesion arising in the cricoid cartilage. A, Axial CT. The chondrosarcoma (C) expands the cricoid cartilage. Small bits of cartilage matrix (arrow) suggest the diagnosis. B, Axial CT bone algorithm. The chondrosarcoma (C) extends up to the superior margin of the cricoid, reaching the cricoarytenoid joint. A, arytenoid. Normal cricoarytenoid joint on opposite side (arrowhead). C, Sagittal CT. The chondrosarcoma (C) expands the cricoid cartilage. V, ventricle. D, The chondrosarcoma (C) reaches the cricoarytenoid and displaces the arytenoid (arrow).

A

B FIG 25-18 Axial CT scan showing chondrosarcoma. A, The tumor expands (arrowhead) the thyroid lamina. B, Note the stippled density (arrow) within the cartilage, representing cartilage formation.

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CT and MR Imaging of the Whole Body The thyroglossal duct cyst arises from the remnant left as the thyroid descends to the appropriate position in the lower neck. Such a cyst can arise above or below the hyoid. Those that arise below the hyoid are usually found just off midline in the region of the strap muscles anterior to the larynx (Fig. 25-22). The appearance is characteristic and should not be confused with a saccular cyst arising within the larynx itself. A thyroglossal duct cyst may rarely bulge over the anterior notch of the thyroid cartilage but should not pass through the lateral aspect of the thyrohyoid membrane. The paraglottic space should not be involved. Any enhancing tissue or nodule within a thyroglossal duct cyst must be considered concerning for malignancy such as papillary thyroid carcinoma.

Posttherapy Imaging

FIG 25-19 Diagram of a laryngocele. Coronal section through the larynx shows the ventricle (arrow) and the ventricular appendix (arrowhead) on the normal side. When this appendix is obstructed, it dilates (ills with either luid or air) to form a saccular cyst or laryngocele. In the diagram the lateral extent of the saccular cyst protrudes through the lateral cricothyroid membrane. (From Curtin HD: The larynx. In Som PM, Bergeron RT, editors: Head and neck imaging, ed 2, St. Louis, 2003, Mosby.)

the abnormality as a saccular cyst if luid illed and as a laryngocele if air illed. Many simply refer to the lesions as air-illed or luid-illed laryngoceles. The laryngocele is a supraglottic abnormality, and the true vocal fold is normal. Both types present as a submucosal mass or bulge in the supraglottic larynx (Figs. 25-20 and 25-21). The air or luid within is readily identiiable, and the extent can be determined. A small saccular cyst or laryngocele may be conined to the supraglottic paraglottic space and is referred to as internal. A larger lesion may protrude laterally through the thyrohyoid membrane just anterior to the upper horn of the thyroid cartilage. Any component outside the membrane is referred to as external. A pure external laryngocele is rare. Occasionally a small air-illed external laryngocele is identiied with no obvious dilatation of the part of the saccule within the paraglottic space. This is usually an incidental inding. The external component is more commonly seen in combination with an internal component. This is called a mixed laryngocele. When the external component is large, the laryngocele can present as a neck mass. Laryngoceles and saccular cysts are benign. However, these abnormalities can occur when tumor in the ventricle causes obstruction of the laryngeal saccule; therefore both the radiologist and the endoscopist must carefully examine this key area. A mucosal cyst is considered to be an obstructed mucous gland and can present anywhere there is mucosa. The benign nature can be suggested by the smooth appearance, and this diagnosis is considered when a cystic-appearing mass is found on a mucosal surface. An oncocytic cyst is considered to be oncocytic metaplasia or degeneration of minor salivary glands of the larynx. These may have a high intrinsic density. This may be mistaken to represent enhancement on contrastenhanced CT scan.

Both surgery and radiotherapy signiicantly distort the normal appearance of the larynx. After a total laryngectomy, the food passage may dilate to mimic an airway, but the laryngeal landmarks are no longer seen. Lower slices show the tracheostomy site. The appearance of the glottic and subglottic levels is unchanged by a supraglottic laryngectomy. The supraglottic larynx has been removed, so the characteristic landmarks of the paraglottic and preepiglottic spaces are not identiied. The hyoid bone may be removed. The major portion of the thyroid cartilage above the level of the vocal fold is also taken. The vertical hemilaryngectomy can give a variable appearance. One vocal fold is removed, leading to signiicant asymmetry at the glottic level. Part of the upper larynx is removed on the ipsilateral side. The position of the original lesion dictates the position of the cuts through the thyroid cartilage, resulting in signiicant variability in appearance among patients with vertical hemilaryngectomies. At times an attempt is made to reconstruct the true vocal fold using a small slip taken from the strap muscles. This can lead to signiicant soft tissue density that cannot be readily distinguished from tumor. With the advent of endoscopic resections, the postoperative appearance of the larynx has become more variable. Close coordination with the surgeon is crucial in understanding these imaging indings. No two resections have the same appearance. Radiotherapy can cause characteristic apparent swelling of the soft tissues over the arytenoids and supraglottic region (Fig. 25-23). Subtle reticulation or stranding of the supraglottic fat is seen. Initially this represents local inlammation and edema, but small vessel changes make the appearance more permanent. Recurrent tumor usually is seen as a small enhancing area that cannot be explained as a postoperative or postradiation change. With further technologic progress and higher resolution, PET may play an expanding role in postoperative assessment of laryngeal tumors.

TRAUMA Direct trauma can result in fractures or dislocations of the cartilages in the larynx.17 Soft tissue injuries such as mucosal tears and hematomas can occur in isolation but are often seen in conjunction with fractures. CT is usually used to evaluate trauma cases because of the ability to visualize the calciied cartilage and because of the speed of imaging. The fragile airway is more easily managed and monitored in the CT scanner than in the more conined area of the MRI machine. In young patients the cartilage may not be calciied but can often be seen as slightly increased density against the contiguous soft tissues. Fractures usually affect the thyroid cartilage or the cricoid cartilage. Fractures of the thyroid cartilage can be vertical or horizontal

CHAPTER 25

L

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L

B

A

L

C

D

L

FIG 25-20 Saccular cyst (luid-illed laryngocele). Postcontrast

E

(Fig. 25-24). The vertical fractures are easily detected in the axial scan plane, but the horizontal fracture may be more dificult to diagnose unless there is some displacement of the fracture fragments. Reformatted images may help deine horizontal fractures. These fractures are less common. The cricoid fracture is characteristically a double break (Fig. 25-25). The force of the blow pushes the anterior arch posteriorly, fracturing the ring in two or more places. The ring collapses inward. There is swelling in the subglottic larynx, with apparent soft tissue against the inner surface of the cricoid cartilage, whereas normally the mucosa is very thin or almost invisible at imaging. The concern is compromise of the airway. Any inward displacement reduces the lumen of the airway. The possibility of a tear of the mucosa is also a concern. A fracture fragment protruding through the mucosa often results in chondritis and chondronecrosis with further airway

CT. A, The luid-illed laryngocele (L) causes a submucosal bulge in the supraglottic larynx. B, Slightly inferiorly the cyst (L) ills much of the paraglottic space but has a smooth margin. C, Just inferior to B the cyst (L) is visible at the false vocal fold level. D, The true vocal fold level is normal. Note the fat (arrow) in the lower paraglottic space along the lateral margin of the thyroarytenoid muscle. E, Coronal reformat shows the cyst (L) in the paraglottic space of the supraglottis. The cyst stops at the level of the ventricle.

restriction. If there is any suspicion of a fragment pushed toward or into the airway, direct visualization via endoscopy or open exploration is indicated to thoroughly assess the mucosa. If there is suficient force to fracture the thyroid cartilage, the lower epiglottis can be torn or avulsed. This can be seen particularly with horizontal fractures where the fragments are pushed posteriorly, creating a shearing force across the lower epiglottis. Because the epiglottis does not calcify signiicantly, this abnormality may not be detectable by CT scans. The only inding may be hematoma obscuring the fat in the preepiglottic space. The curve of the epiglottis can often be outlined against the preepiglottic fat in the sagittal plane, so sagittal reformatted images can be helpful in evaluating trauma cases. The arytenoid cartilage is not often fractured, but the cricoarytenoid joint can be dislocated. This can occur with fairly minimal trauma to the lateral larynx or result from a more signiicant insult associated

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C

B

A

FIG 25-21 Saccular cyst (laryngocele). A, The cystic structure has both an internal and an external component. The saccular cyst (C) protrudes through the thyrohyoid membrane (approximately at arrowheads). Note the sharp margin of the cyst. B, Slightly lower slice shows the dilated appendix (arrow) just above the ventricle. Again note the sharp margin. The fat in the paraglottic space indicates that this is still above the ventricle. Normal appendix is on the opposite side (arrowhead).

H E

B

A

FIG 25-22 Thyroglossal duct cyst. Postcontrast CT. A, Axial image shows cyst (arrows) along the outer lamina of the thyroid cartilage embedded in the prelaryngeal strap muscles. B, Sagittal image shows the cyst bulging between the thyroid cartilage and hyoid bone (H). The cyst attaches to the posterior margin of the hyoid (arrow). E, epiglottis.

with fractures of the major cartilages. The arytenoid is normally perched just off midline. The radiologist tries to verify that the cartilage is in the normal position or grossly displaced. Currently a subtle displacement cannot be conidently excluded. The lower horns of the thyroid cartilage articulate with the lateral cricoid cartilage. This cricothyroid joint can be dislocated, usually in association with fractures of either the thyroid or cricoid cartilages. Because the attachment of the horn (cornua) to the cricoid cartilage is fairly strong, a fracture of the lower horn is considered to be more common than dislocation. One must be careful in making this diagnosis; slight obliquity of the slice can cause apparent asymmetry of the space between the two cartilages. Each of the inferior horns must be followed down to the point of articulation.

MISCELLANEOUS PATHOLOGY Although tumors and trauma account for most imaging of the larynx, there are several other problems for which imaging can be useful.

Vocal Cord Paralysis Vocal cord paralysis is most commonly a problem affecting the recurrent laryngeal nerve. This nerve innervates all the muscles in the larynx except the cricothyroid muscle. The most common characteristic imaging indings are the result of atrophy of the TAM. Normally this muscle makes up the bulk of the true cord. With atrophy the characteristic CT density or MRI intensity shape is either smaller or no longer seen (Fig. 25-26). The ventricle enlarges into the volume vacated by

CHAPTER 25

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E A

A

B

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D FIG 25-23 Postradiation change. Postcontrast CT. A, Scout view for CT shows the thickened epiglottis (E) and swollen arytenoid (A) prominence. B, Axial image through the level of the thickened epiglottis. C, Axial image at the level of the aryepiglottic folds shows pronounced swelling (arrow). D, Swollen supraglottis (arrows).

FIG 25-25 Fracture of the cricoid cartilage. The ring has been fractured, FIG 25-24 Axial CT scan of vertical fracture of the larynx. Arrow indicates fracture.

and fragments from the anterior ring (arrowheads) have been pushed back into the airway. These fragments would be in danger of perforating the mucosa. The lamina of the cricoid (arrow) is not fractured. Note the air in the soft tissues and the soft tissue within the ring of the cricoid cartilage. (From Curtin HD: MR and CT of the larynx. In Thrall JH, editor: Current practice of radiology, ed 3, St. Louis, 1994, Mosby.)

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A

FIG 25-27 Vocal fold injection. Radiodense injection (Gore-Tex) (arrow)

A

B

C FIG 25-26 Vocal fold paralysis, recurrent nerve. A, Axial T1-weighted image. The ventricle is enlarged (arrow) as the thyroarytenoid muscle (TAM) atrophies. Arrowhead indicates arytenoid. B, Axial T1 image, slightly lower than A. The posterior cricoarytenoid muscle has atrophied and is replaced by fat (arrow). Note the normal posterior cricoarytenoid muscle (arrowhead) on the opposite side. C, Coronal reformatted CT image. The ventricle (arrowhead) has enlarged as the TAM (arrow) atrophies. The vocal cord (fold) is more pointed on the abnormal side.

displaces the true vocal fold medially. The arytenoid (A) is also slightly rotated.

the atrophied muscle, so air can be seen where there should be muscle. The vocal ligament remains, so the arytenoid may be in a fairly normal position or it may be tipped slightly. The pyriform sinus on the affected side often enlarges as well. These indings can be visualized in both the axial or coronal planes. The posterior cricoarytenoid muscle is very thin, but because the axial plane provides a perfect cross section, atrophy of this muscle may also be appreciated.29 The muscle is located along the posterior aspect of the cricoid cartilage. In this case, fat is seen closely applied to the posterior surface of the cricoid cartilage instead of the typical muscle density (see Fig. 25-26). Surgical treatment of a vocal fold paralysis may include injection of various materials or even placement of fat to add bulk to the paralyzed vocal fold (Fig. 25-27). Prostheses have been designed to add bulk and reposition the arytenoid (Fig. 25-28). In most instances, atrophied muscle is seen in a patient with known paralysis. The diagnosis is usually made by direct visualization by mirror or ofice endoscopy. If the cause of the paralysis is not known, the course of the vagus nerve and the recurrent laryngeal nerve is examined. CT is usually performed because of the distance that must be covered and because bone detail is helpful at the level of the jugular foramen in the temporal bone. The vagus nerve is just posterior to the carotid artery and jugular vein on transit through the neck. Lower in the neck, the nerve moves forward with respect to the carotid. The left recurrent laryngeal nerve loops around the aortic arch and the right around the subclavian artery. The nerve on both sides ascends along the tracheoesophageal groove to reach the larynx. A lesion at any level can involve the nerve and cause paralysis. Superior laryngeal nerve paralysis is much less common, and characteristic radiographic indings have not been described.

Stenosis Subglottic stenosis and tracheal stenosis can be evaluated by plain ilms, but sectional imaging can give information about the crosssectional area of the remaining airway. CT can show narrowing or stenosis of anterior and posterior commissures. The position of the cartilage relative to the airway can also be visualized. CT scans can determine whether the cartilage has collapsed into the airway or whether the cartilage remains in the normal position, with the stenosis the result of soft tissue within the cartilage ring (Fig. 25-29). Such narrowing can be congenital or the result of trauma. Stenosis can follow prolonged intubation. Granulation tissue can develop after

CHAPTER 25

A

Larynx

B

A

C

D FIG 25-28 Prosthesis for repositioning paralyzed vocal fold. Axial CT from inferior to superior. A, The prosthesis (arrow) is “popped” into a defect cut through the thyroid cartilage. A small ridge is present at each margin to hold the prosthesis in place. B, Slightly superior to A. C, Slightly superior to B. The arytenoid (A) is pushed medially. D, Superior to C. The tip of the prosthesis (arrowhead) projects posteriorly.

E

A

B

FIG 25-29 Subglottic stenosis. History of prolonged intubation. A, Axial postcontrast CT at the level of the lower cricoid cartilage. There is soft tissue (arrowheads) along the inner cortex of the cricoid cartilage (arrow) that is not collapsed into the airway. This is a “soft” stenosis. B, Coronal reformat airway “cast” showing the level and extent of the narrowing. Note the level of the anterior commissure and ventricle (arrowhead). E, epiglottis.

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tracheostomy. The length of the narrowing and the relationship to the vocal folds should be estimated. Plain ilms can be very helpful in estimating the length of the abnormality, but this information can easily be derived from reformatting of images from CT.

Granulomatous Disease and Inlammation Granulomatous disease, either of infectious or noninfectious etiology, can involve the larynx.17 Though rare, it can involve any of the mucosal surfaces and can be mistaken for tumor. The indings at imaging are nonspeciic. Tuberculosis usually occurs with concurrent pulmonary disease. Radiation causes an apparent inlammatory response with swelling of the supraglottis (see Fig. 25-23). Rarely adult supraglottitis can cause severe swelling, predominantly of the supraglottis. More subtle changes can be seen with severe gastroesophageal relux extending to the pharynx and larynx.

Rheumatoid Arthritis Rheumatoid arthritis can involve the cricoarytenoid joint. This process is not usually evaluated radiologically.

Polychondritis Relapsing polychondritis is a rare disease of unknown etiology. The cartilages of the larynx and trachea (among others) become inlamed, with edema of surrounding tissues. The cartilages may actually appear to enlarge. Calciications of the abnormal tissue are characteristic and can be very prominent. If particularly extensive, the increased soft tissues and calciications can mimic chondroid lesions.

SUMMARY CT or MRI can be used for tumor imaging. One approach is to use CT as the initial imaging evaluation, reserving MRI for answering speciic questions remaining after CT. MRI is then done in a small fraction of cases directed at a limited speciic part of the tumor. Contrast-enhanced CT scans are preferred for imaging of submucosal masses. CT scans are done without enhancement in trauma cases.

REFERENCES 1. Agrawal N, Ha PK: Management of early-stage laryngeal cancer. Otolaryngol Clin North Am 41:757–769, vi–vii, 2008. 2. Barbu AM, Burns JA, Lopez-Guerra G, et al: Salvage endoscopic angiolytic KTP laser treatment of early glottic cancer after failed radiotherapy. Ann Otol Rhinol Laryngol 122:235–239, 2013. 3. Barnes L: Diseases of the larynx, hypopharynx, and esophagus. In Barnes L, editor: Surgical pathology of the head and neck, ed 2, New York, 2001, Marcel Dekker, pp 127–237. 4. Becker M, Burkhardt K, Dulguerov P, et al: Imaging of the larynx and hypopharynx. Eur J Radiol 66:460–479, 2008. 5. Becker M, Moulin G, Kurt AM, et al: Non-squamous cell neoplasms of the larynx: Radiologic-pathologic correlation. Radiographics 18:1189– 1209, 1998. 6. Becker M, Zbaren P, Casselman JW, et al: Neoplastic invasion of laryngeal cartilage: Reassessment of criteria for diagnosis at MR imaging. Radiology 249:551–559, 2008. 7. Becker M, Zbaren P, Delavelle J, et al: Neoplastic invasion of the laryngeal cartilage: Reassessment of criteria for diagnosis at CT. Radiology 203:521–532, 1997. 8. Becker M, Zbaren P, Laeng H, et al: Neoplastic invasion of the laryngeal cartilage: Comparison of MR imaging and CT with histopathologic correlation. Radiology 194:661–669, 1995.

9. Castelijns JA, Gerritsen GJ, Kaiser MC, et al: MRI of normal or cancerous laryngeal cartilages: Histopathologic correlation. Laryngoscope 97:1085–1093, 1987. 10. Castelijns JA, van den Brekel MW, Smit EM, et al: Predictive value of MR imaging-dependent and non-MR imaging-dependent parameters for recurrence of laryngeal cancer after radiation therapy. Radiology 196:735–739, 1995. 11. Curtin HD: Imaging of the larynx: Current concepts. Radiology 173:1–11, 1989. 12. Curtin HD: Anatomy, imaging, and pathology of the larynx. In Som PM, Curtin HD, editors: Head and neck imaging, ed 5, Philadelphia, 2011, Mosby, pp 1905–2039. 13. Dadfar N, Seyyedi M, Forghani R, et al: Computed tomography appearance of normal nonossiied thyroid cartilage: Implication for tumor invasion diagnosis. J Comput Assist Tomogr 39:240–243, 2015. 14. Dubal PM, Svider PF, Kanumuri VV, et al: Laryngeal chondrosarcoma: A population-based analysis. Laryngoscope 124:1877–1881, 2014. 15. Forghani R, Levental M, Gupta R, et al: Different spectral Hounsield unit curve and high energy virtual monochromatic image characteristics of squamous cell carcinoma compared to non-ossiied thyroid cartilage. AJNR Am J Neuroradiol 2015. In press. 16. Franco RA, Jr, Singh B, Har-El G: Laryngeal chondroma. J Voice 16:92–95, 2002. 17. Glastonbury CM: Non-oncologic imaging of the larynx. Otolaryngol Clin North Am 41:139–156, vi, 2008. 18. Gray H, Strandring S, Ellis H, et al: Gray’s anatomy: The anatomical basis of clinical practice, Edinburgh, 2005, Elsevier Churchill Livingstone. 19. Huang BY, Solle M, Weissler MC: Larynx: Anatomic imaging for diagnosis and management. Otolaryngol Clin North Am 45:1325–1361, 2012. 20. Kirchner JA: Two hundred laryngeal cancers: Patterns of growth and spread as seen in serial section. Laryngoscope 87:474–482, 1977. 21. Kuno H, Onaya H, Iwata R, et al: Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma with dualenergy CT. Radiology 265:488–496, 2012. 22. Lawson W, Biller H, Suen J: Cancer of the larynx. In Suen J, Myers E, editors: Cancer of the head and neck, New York, 1989, Churchill Livingstone, pp 533–591. 23. Ljumanovic R, Langendijk JA, Hoekstra OS, et al: Pre- and postradiotherapy MRI results as a predictive model for response in laryngeal carcinoma. Eur Radiol 18:2231–2240, 2008. 24. Ljumanovic R, Langendijk JA, van Wattingen M, et al: MR imaging predictors of local control of glottic squamous cell carcinoma treated with radiation alone. Radiology 244:205–212, 2007. 25. Loehn BC, Kunduk M, McWhorter AJ: Advanced laryngeal cancer. In Johnson JT, Rosen CA, Bailey BJ, editors: Bailey’s Head and Neck Surgery—Otolaryngology, ed 5, Philadelphia, 2013, Wolters Kluwer Health/Lippincott Williams & Wilkins, pp 1961–1977. 26. Mancuso AA, Mukherji SK, Schmalfuss I, et al: Preradiotherapy computed tomography as a predictor of local control in supraglottic carcinoma. J Clin Oncol 17:631–637, 1999. 27. Maroldi R, Ravanelli M, Farina D: Magnetic resonance for laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg 22:131–139, 2014. 28. Pilch BZ: Head and neck surgical pathology, Philadelphia, 2001, Lippincott Williams & Wilkins. 29. Romo LV, Curtin HD: Atrophy of the posterior cricoarytenoid muscle as an indicator of recurrent laryngeal nerve palsy. AJNR Am J Neuroradiol 20:467–471, 1999. 30. Sakai O, Curtin HD, Faquin WC, et al: Dedifferentiated chondrosarcoma of the larynx. AJNR Am J Neuroradiol 21:584–586, 2000. 31. Sinha P, Okuyemi O, Haughey BH: Early laryngeal cancer. In Johnson JT, Rosen CA, Bailey BJ, editors: Head and neck surgery—Otolaryngology, ed 5, Philadelphia, 2013, Wolters Kluwer Health /Lippincott Williams & Wilkins, pp 1940–1960. 32. Tucker GF, Jr, Smith HR, Jr: A histological demonstration of the development of laryngeal connective tissue compartments. Trans Am Acad Ophthalmol Otolaryngol 66:308–318, 1962.

CHAPTER 25 33. Tufano RP, Stafford EM: Organ preservation surgery for laryngeal cancer. Otolaryngol Clin North Am 41:741–755, vi, 2008. 34. Zan E, Yousem DM, Aygun N: Asymmetric mineralization of the arytenoid cartilages in patients without laryngeal cancer. AJNR Am J Neuroradiol 32:1113–1118, 2011. 35. Zeitels SM, Burns JA: Oncologic eficacy of angiolytic KTP laser treatment of early glottic cancer. Ann Otol Rhinol Laryngol 123:840–846, 2014.

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36. Zeitels SM, Kirchner JA: Hyoepiglottic ligament in supraglottic cancer. Ann Otol Rhinol Laryngol 104:770–775, 1995. 37. Zeitels SM, Wain JC, Barbu AM, et al: Aortic homograft reconstruction of partial laryngectomy defects: A new technique. Ann Otol Rhinol Laryngol 121:301–306, 2012.

26 Imaging of the Head and Neck in the Pediatric Patient Indu Rekha Meesa and Suresh Mukherji

INTRODUCTION The old adage that “children are not young adults” is certainly true when evaluating pediatric head and neck lesions. The differential diag­ nosis of neck masses differs compared to masses that arise in adults. The most common pediatric head and neck lesions are congenital or developmental in origin, followed by inlammatory processes and tumors. This chapter will focus on the congenital/developmental and neoplastic processes; inlammatory lesions are covered in other chapters.

BENIGN CONGENITAL MASSES OF THE NECK Thyroglossal duct cysts (TDCs) and anomalies of the branchial appa­ ratus are the most common benign masses of the neck in children. Less common congenital benign masses of the head and neck in the pedi­ atric age group include dermoid/epidermoid cysts and teratomas.54

Thyroglossal Duct Cyst TDC is the most common congenital neck mass and accounts for nearly 90% of nonodontogenic congenital cysts.217 TDC is the second most common benign cervical mass in children after reactive ade­ nopathy and almost three times more common than branchial cleft cysts.54,148,204,206

Embryogenesis of Thyroglossal Duct. At about 3 weeks’ gestation, the thyroid gland begins to develop as a midline endodermal diverticu­ lum from the loor of the pharynx, and over the following 4 weeks of development, the primitive thyroid gland enlarges to form a bilobed diverticulum.54 For a short period of time, the developing thyroid gland is connected to the tongue by a narrow tube, the thyroglossal duct.195 This duct courses from the region of the junction of the ante­ rior two thirds and posterior two thirds of the tongue (foramen cecum) to the hyoid bone and farther caudally to the region of the future loca­ tion of the pyramidal lobe of the thyroid gland in the inferior neck.195 A TDC or istula forms when a portion of this duct fails to involute and leaves behind rests of secretory epithelial cells that when stimu­ lated by an inlammatory process cause a cyst to develop.195

Presentation. The TDC is usually a midline or near­midline lesion and can occur anywhere along the path of the duct. About 20% to 25% occur in the suprahyoid neck, 15% to 50% at the level of the hyoid bone, and 25% to 65% in the infrahyoid neck.159 They commonly occur near the hyoid bone and can be superior, anterior, inferior, or posterior to this bone.195 TDCs usually present in the irst 5 years of life, with about 66% noted before age 7 and 90% before age 10.54 A small percentage are diagnosed

754

in patients older than 50 years. Patients typically present with a history of a gradually enlarging mass in the midline or paramedian neck and demonstrate a nontender, mobile, 2­ to 4­cm subcutaneous midline or paramedian neck mass of variable irmness. Other presentations include complications of cyst infection, istula formation, or rupture.54 The lining of the cyst may be stratiied squamous, pseudostratiied ciliated, simple cuboidal, or columnar epithelium, and there may be residual thyroid tissue in the enlarging mass in the midline of the neck.195 Coexisting carcinoma in the wall of the cyst is reported in less than 1% of patients with TDC and typically occurs in adults, with papillary carcinoma being most common followed by papillary­ follicular carcinoma.3,11,23,35

Imaging Findings. Suprahyoid neck cysts are almost always in the midline. When the cysts occur just caudal to the hyoid bone at the level of the thyrohyoid membrane of the larynx, they can stretch this mem­ brane and bow it posteriorly, appearing to lie in the preepiglottic space of the larynx. In the infrahyoid neck, the cyst lies just off the midline, adjacent to the outer surface of the thyroid cartilage and deep to the infrahyoid strap muscles.195 In the pediatric population, initial imaging evaluation is frequently performed with ultrasound, which demonstrates a well­deined, thin­ walled, midline or paramedian mass with increased through transmis­ sion and variable internal echogenicity and no internal blood low. Increased internal echogenicity can be due to multiple factors includ­ ing inlammatory debris, hemorrhage, or proteinaceous content.120,216 On computed tomography (CT), the TDC appears as a mass of relatively decreased attenuation to muscle. When the cyst is not infected, it will also demonstrate a thin, smooth rim, but when infected the cyst wall thickens and enhances (Fig. 26­1). The attenuation of the cyst will vary based on its contents; usually they will have mucoid attenuation (10­25 Hounsield units [HU]), but if there has been pre­ vious infection or hemorrhage, attenuation of the cyst contents can approach that of muscle.195 On magnetic resonance imaging (MRI) the T1 signal intensity can vary from low to high, while T2 signal intensity remains high. The variations in signal intensity are based on the vari­ able protein content of the cyst. With infection or hemorrhage, septa­ tions can also arise in the cyst. A TDC with an internal eccentric solid mass containing calciica­ tions or iniltrative soft tissue characteristics should raise concern for an associated carcinoma.54 The primary differential considerations of TDC by imaging include dermoid/epidermoid cyst, branchial cleft cyst (if paramedian in loca­ tion), or rarely a sebaceous cyst.148

Treatment. Treatment is surgical removal of all tissue along the course of the duct as far as the foramen cecum (Sistrunk procedure).

CHAPTER 26

Imaging of the Head and Neck in the Pediatric Patient

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B

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FIG 26-1 Thyroglossal duct cyst (TDC). A, Axial contrast-enhanced CT image at the level of the hyoid bone demonstrates a large midline nonenhancing low-attenuation mass (arrows), most consistent with a TDC. B, Axial contrast-enhanced CT image at the level of the hyoid bone demonstrates a large midline predominantly low-attenuation mass with some enhancing components centrally (arrows), concerning for a TDC complicated by papillary thyroid carcinoma.

The hyoid bone rotates during maturation before assuming its inal adult position. During this rotation, the thyroglossal duct is adherent to the hyoid along its anterior inferior edge and may be drawn poste­ riorly and cranially to lie behind the body of the hyoid bone; rarely the duct can be incorporated into the hyoid bone, trapped between the second and third arch components of the hyoid’s body.15,58 Owing to this close relationship between the body and the TDC, Sistrunk pro­ posed that the body of the hyoid bone should be removed during surgi­ cal resection of a thyroglossal duct, leading to a signiicant decrease in recurrences, reduced from nearly 50% to less than 4%.186

Anomalies of the Branchial Apparatus Embryogenesis of the Branchial Apparatus. The anatomic struc­ tures of the face and neck predominantly derive from the branchial apparatus, which is a complex structure derived from neural crest cells that develops between the second and seventh weeks of gestation.27,54 The branchial apparatus consists of six paired arches separated on their outer surface by ive paired ectodermal clefts and on their inner surface by ive paired endodermally derived pharyngeal pouches.27 By the end of the fourth week of life, four well­deined pairs of arches are visible and the ifth and sixth arches are rudimentary. Each arch is composed of a central core of mesoderm and is lined externally by ectoderm and internally by endoderm. The cervical sinus of His is formed after the branchial arches appear by accelerated mesodermal growth cranially of the irst arch and a portion of the second arch, and caudally by growth of the epipericar­ dial ridge, which develops from the mesoderm lateral to the ifth­sixth arch. The branchial apparatus typically disappears between the fourth and sixth weeks of life.27

Etiology of Branchial Anomalies. The etiology of branchial anom­ alies is controversial, and the most accepted theories to explain the

development of branchial abnormalities propose that they are either vestigial remnants from incomplete obliteration of the branchial appa­ ratus or the result of buried epithelial cell rests.126,29

Classiication. Anomalies of the branchial apparatus are best under­ stood by being classiied into a spectrum of developmental anomalies that includes istulas, sinuses, and cysts.195

First Branchial Anomalies. First branchial cleft anomalies account for up to 5% to 8% of all branchial anomalies: 68% are cysts, 16% are sinuses, and 16% are istulas.51,63,139 Although Arnot and Work tried to subclassify irst branchial anomalies into two distinct subtypes in 1971 and 1972, Olsen—after reviewing multiple cases—concluded that it is dificult to subclassify all these anomalies into one of the subtypes and proposed a simpliied classiication (cysts, sinuses, and istulas).70,152,183,209,224 Embryology. The irst branchial apparatus gives rise to portions of the middle ear, external auditory canal, eustachian tube, mandible, and maxilla, and the formation of these structures is completed by the sixth and seventh weeks of gestation.54 The parotid gland and facial nerve form and migrate between the sixth and eighth weeks of gestation. Because the facial nerve and parotid gland have a somewhat later embryologic development, vestigial branchial anomaly can be located in variable relationship to the parotid gland and the facial nerve.195 First branchial apparatus anomalies arise from incomplete closure of the ectodermal portion of the irst branchial cleft. They can start at the junction of the bony and cartilaginous external auditory canal or in the cartilaginous portion of the external canal, the plane between the mandibular and hyoid arches, and end in the subman­ dibular area. As a result, irst branchial apparatus anomalies can arise in the middle ear cavity, external auditory canal, supericial or deep lobes of the parotid gland, supericial to the parotid gland, at the

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PART II CT and MR Imaging of the Whole Body

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angle of the mandible, anterior or posterior to the pinna, or along the nasopharynx.14,209 Presentation. Although the majority of irst branchial apparatus anomalies occur in the irst decade of life, they can also be encountered in middle­aged patients, especially women. Patients typically present with recurrent abscesses or inlammatory processes with tenderness and swelling at the angle of the mandible or in the ear. If the process is related to the parotid gland, patients tend to present with recurrent parotid abscesses not responding to therapy. If there is drainage of the cyst into the external auditory canal, the initial presentation is typically otorrhea.54 Simple cysts can also present as a painless soft tissue mass. Sinus tracts are rare with irst branchial anomalies. When present, they are usually found in the irst decade of life.204 Imaging findings. First branchial cysts are usually related to the parotid gland, external canal of the ear, and/or the lower margin of the pinna or at the angle of the mandible.54 If a tract can be identi­

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FIG 26-2 First branchial cleft anomaly. A, Coronal contrastenhanced CT image demonstrates a low-attenuation lesion (arrow) within the right parotid gland associated with asymmetric enlargement and high attenuation. B, Axial T2-weighted MRI at the level of the parotid gland demonstrates a rounded T2 bright lesion (arrow) within the right parotid gland. C, Coronal T1 postcontrast MRI demonstrates a nonenhancing cystic lesion in the right parotid gland, associated with asymmetric enlargement and enhancement of the parotid tissue secondary to an inlamed branchial cleft cyst (arrows).

ied, directed toward the external auditory canal, then the diagnosis can be made with certainty. If a tract is not seen and the cyst lies within the parotid gland, possibilities would include a irst branchial cyst, parotid suppurative lymph node and abscess, inlamed ectatic salivary gland, a lymphoepithelial cyst (human immunodeiciency virus [HIV]), Sjögren’s syndrome, or a rare localized obstructive mucocele.54,105,195 Uncomplicated cysts demonstrate mild rim enhancement or no enhancement. Infected cysts have variable wall thickness and enhance­ ment characteristics (Fig. 26­2). If the anomaly is located within the parotid gland, the imaging indings will be nonspeciic. For example, the cyst contents of a irst branchial cyst, a lymphoepithelial cyst, or an obstructive mucocele or sialocele are usually of mucoid attenuation on CT, and on MRI usually have low to intermediate T1­weighted and high T2­weighted signal intensity.195 T2­weighted or short tau inver­ sion recovery (STIR) MRI sequences may be helpful in identiication

Imaging of the Head and Neck in the Pediatric Patient

CHAPTER 26

of small luid­illed tracts leading to the external auditory canal.54 If the cyst is infected and has a tract, coronal T2­weighted and postcon­ trast T1­weighted fat­suppressed MRIs would best demonstrate the tract.195 Treatment. Treatment is complete surgical resection and carries an excellent prognosis. The major complication of surgery is related to facial nerve injury. Residual wall remnants can lead to recurrence.54

Second Branchial Anomalies. About 95% of all branchial anoma­ lies are related to the second branchial apparatus, and these anomalies can occur anywhere from the tonsillar fossa to the supraclavicular region of the neck.54,80 The majority of these anomalies, about three fourths, are cysts.205 Cysts are more common between 10 and 40 years of age, and istulas or sinuses usually present before age 10.133,194 Classification. Second branchial cysts are classiied into four sub­ types based on location per Bailey’s classiication. Type 1 cyst lies deep

to the platysma muscle and anterior to the sternocleidomastoid (SCM) muscle (Fig. 26­3). This type of cyst is felt to represent a remnant of the tract between the sinus of His and the skin. Type II cyst is the most common type and is thought to be the result of the persistence of the sinus of His. This cyst is located posterior and lateral to the subman­ dibular gland, anterior and medial to the SCM muscle, and anterior and lateral to the carotid space (Fig. 26­4). Type III cyst/istula is thought to arise from a dilated pharyngeal pouch and courses medially between the internal and external carotid arteries; it can extend up to the lateral wall of the pharynx or skull base (Fig. 26­5). Type IV cyst lies in the mucosal space of the pharynx adjacent to the pharyngeal wall and is thought to arise from a remnant of the pharyngeal pouch5,54,135,147,179 (Fig. 26­6). Presentation. The most common presentation of a second bran­ chial cleft cyst is as a luctuant nontender mass at the lateral aspect of the mandibular angle.135,191,194 When infected the patient will present

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FIG 26-3 Second branchial cleft anomaly, type 1. A, Axial contrast-enhanced CT image at the level of the thyroid cartilage demonstrates a nonenhancing rounded lesion (arrow) adjacent to the strap muscle. B, Axial contrast-enhanced CT image at the level of the thyroid gland demonstrates inlammatory changes along the platysma and adjacent to the left sternocleidomastoid muscle (arrows).

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FIG 26-4 Second branchial cleft anomaly, type 2. Axial (A), coronal (B), and sagittal (C) contrast-enhanced CT images at the level of the submandibular gland demonstrate a rounded luid-attenuation lesion located anterior to the right sternocleidomastoid muscle, anterolateral to the carotid space and posterior to the submandibular gland, resulting in mild mass effect and anterior displacement of the right submandibular gland (arrows).

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PART II CT and MR Imaging of the Whole Body

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D FIG 26-5 Second branchial cleft anomaly, type 3. Axial contrast-enhanced CT images demonstrate an enhancing istulous tract extending from the left tonsillar fossa (A) to the skin surface at the left of the sternocleidomastoid (SCM) muscle (B) in the lower neck (arrows). Coronal CT image of the istula injection demonstrates a tract extending from the right tonsillar region (C) to the right SCM and carotid jugular sheath (D) (arrows).

with a history of a slowly enlarging painful mass. Because the cysts contain lymphoid tissue, stimulus such as an upper respiratory tract infection can lead to an increase in size of the cyst.54 With a istula, an ostium is often noted at birth at the anterior border of the junction of the middle and inferior thirds of the SCM muscle. The tract then courses deep to the platysma muscle, ascends laterally along the carotid sheath, lateral to the hypoglossal and glossopharyngeal nerves, and then passes between the internal and external carotid arteries before it terminates in the region of the palatine tonsillar fossa.5,14 Imaging findings. Ultrasound is usually the initial imaging study because the cysts often present as a neck mass in a young child and can range in size from 1 to 10 cm.5,14,46,54,205 If the anomaly is uncomplicated

it will demonstrate sonographic characteristics of a simple cyst (thin wall, increased through transmission, anechoic, and compressible). On CT the anomaly will demonstrate a thin wall with decreased attenua­ tion. On MRI it will appear as hypointense to slightly hyperintense to muscle on T1­weighted images and hyperintense to muscle on T2­weighted images. When it is infected it can demonstrate a thicker wall with increased internal echogenicity on ultrasound, increased attenuation on CT, and hyperintense T1­weighted signal on MRI, with variable enhancement. If the cysts are chronically complicated, they can demonstrate septations.14,80,135,139,204 Sometimes there may be a “beak sign” present, which is pathogno­ monic of a Bailey type III second branchial cyst, where the medial

CHAPTER 26

Imaging of the Head and Neck in the Pediatric Patient

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FIG 26-6 Second branchial cleft anomaly, type 4. Axial (A) and coronal (B) contrast-enhanced CT images demonstrate a rounded nonenhancing cystic lesion in the right tonsillar fossa (arrows).

aspect of the cyst is compressed and forms a beak as it extends between the internal and external carotid arteries on axial CT or MRI.78 In children, differential considerations include suppurative adenopathy/deep neck infection, lymphatic malformation, dermoid/ epidermoid cyst, and thymic cyst. Other rare considerations in this age group include cystic schwannoma of the vagal nerve, minor salivary gland tumor, and necrotic malignant adenopathy.80,143,181 Because the jugulodigastric node is seen in the same location as the most common form of second branchial cleft cyst, clinicians may mistake it for an enlarged, suppurative, reactive, or tumor­iniltrated jugulodigastric node.78 Treatment. Treatment is complete surgical resection, which carries an excellent prognosis.54

Third and Fourth Branchial Anomalies. These are rare anomalies, and third branchial anomalies account for 3% and fourth branchial anomalies account for about 1% to 2%.40 Third branchial anomalies are centered in the posterior cervical space, and despite their overall rarity they are the second most common congenital lesions of the posterior cervical space after lymphatic malformation. These must sometimes be distinguished from the large second branchial cleft cyst, which can protrude posteriorly in the posterior cervical space.54 Embryology. Third branchial anomalies most likely arise second­ ary to failure of involution of the third branchial apparatus, and fourth branchial anomalies are likely due to failure of regression of the fourth branchial pouch or distal sinus of His.40,155 Third branchial apparatus cysts are located posterior to the common carotid or internal carotid artery, between the hypoglossal nerve (below) and glossopharyngeal nerve (above). If it is in the form of a istula, there will be a cutaneous opening similar to a second branchial istula that is anterior to the lower SCM muscle. It then courses pos­ terior to the common or internal carotid artery, anterior to the vagus nerve and between the hypoglossal and glossopharyngeal nerves, and then pierces the thyrohyoid membrane and enters the pyriform sinus anterior to the superior laryngeal nerve.54 Presentation and imaging findings. Third branchial cleft cysts usually present as painless, luctuant, 2­ to 5­cm masses in the pos­ terior triangle of the neck, often after a viral upper respiratory infec­

FIG 26-7 Third branchial cleft anomaly. Postcontrast axial CT image at the level of the mandible demonstrates a low-attenuation lesion in the posterior cervical space posterior to the carotid vessels and the sternocleidomastoid muscle (arrow).

tion (Fig. 26­7). The presentation is at an earlier age with a sinus or a istula. On CT and MRI, uncomplicated cysts usually present as a unilocular cystic mass on imaging, and complicated cysts demonstrate increased wall thickness with variable enhancement characteristics and internal proteinaceous luid.54 Anomalies related to the fourth branchial pouch are usually in the form of a sinus tract that arises from the pyriform sinus, pierces the

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PART II CT and MR Imaging of the Whole Body

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D FIG 26-8 Fourth branchial cleft anomaly. A, Contrast-enhanced axial CT image at the level of the thyroid gland demonstrates abnormal low attenuation, enlargement, and enhancement of the left thyroid lobe (arrow). Axial T2-weighted (B) and contrast-enhanced T1-weighted (C) MRIs demonstrate abnormal signal and enhancement with inlammatory changes in the left thyroid lobe (arrows). D, Esophagram demonstrates a sinus tract from the left pyriform sinus (arrow).

thyrohyoid membrane, descends along the tracheoesophageal groove, and continues into the mediastinum. These anomalies have variant presentations such as a nontender luctuant mass anterior to the infe­ rior SCM muscle for uncomplicated cases, and suppurative thyroiditis or recurrent neck abscesses for complicated cases54 (Fig. 26­8). For diagnosing a istulous tract by imaging, a contrast­enhanced CT fol­ lowing ingestion of barium or water­soluble contrast or direct injec­ tion of a istulous tract is the imaging study of choice.54 Although it is dificult to differentiate third from fourth branchial anomalies by imaging alone, the key anatomic markers for correctly diagnosing them include the carotid artery and the superior laryngeal nerve. Third branchial anomalies lie posterior to the internal carotid

artery and above the superior laryngeal nerve, whereas fourth bran­ chial anomalies are anterior to the internal carotid artery and lie below the superior laryngeal nerve.8,54 Third and fourth branchial anomalies can be related to the pyriform sinus and can appear similar to external laryngoceles on imaging.54 Other differential considerations for third and fourth branchial anomalies include other branchial anomalies, TDC, lymphatic malfor­ mation, thyroid abscess, thyroid, parathyroid, or thymic cyst, and sup­ purative adenopathy.14,139 Treatment. For both third and fourth branchial anomalies, com­ plete surgical resection is the treatment of choice. Persistence of the tract to the pyriform sinus can result in recurrent episodes of

CHAPTER 26

Imaging of the Head and Neck in the Pediatric Patient

thyroiditis and can necessitate a partial thyroidectomy. If fourth bran­ chial anomalies are complicated by infection and secondary thyroiditis, medical treatment should precede surgical treatment.54

Cervical Thymic Remnant Embryology and etiology. Cervical thymic remnants are very rare lesions, and two main theories, congenital theory and acquired theory, have been reported to explain their etiology.54 The congenital theory states that the cysts are due to persistence of thymopharyngeal duct remnants and can be located anywhere from the level of the pyriform sinus to the superior mediastinum and located either beneath or medial to the SCM muscle. The acquired theory for thymic cysts pro­ poses progressive cystic degeneration of thymic (Hassall’s) corpuscles, primitive endodermal cells, lymphocytes, and epithelial reticulum of the thymus as sources for thymic remnants. Presentation. The thymus reaches its greater relative size at age 2 to 4 years and its greatest absolute size at puberty. Cervical thymic remnants are very rare lesions and can be found anywhere along the path of the thymopharyngeal duct. Most are detected in childhood, and two thirds are found in the irst decade of life, often between 3 and 8 years of age, and the remain­ der in the second and third decades of life.22,78,194,219 Most patients are asymptomatic, and about 80% to 90% present with a painless slowly enlarging neck mass near the thoracic inlet, anterior or deep to the SCM muscle.41,52,57,59 In 50% of cases, a connec­ tion between the cervical thymic anomaly and the mediastinal thymic gland occurs in the form of direct extension or a remnant of the thy­ mopharyngeal duct.54 Mediastinal thymic cysts can occur without a cervical component. There is a frequent association between cervical thymic cysts and thyroid and parathyroid inclusion cysts, and a ibrous strand is sometimes present between the cervical thymic cyst and the thyroid gland.8,57 Imaging findings. Because most ectopically located thymic masses are often cystic on ultrasound, CT and MRI will demonstrate imaging characteristics consistent with an uncomplicated cyst. A cystic lesion will course parallel to the SCM muscle and along the carotid sheath or lateral aspect of the visceral space on CT (Fig. 26­9). Imaging charac­ teristics will vary if the cysts are complicated by hemorrhage, choles­ terol, proteinaceous luid, or infection.22,194 Aberrant thymic tissue,

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parathyroid tissue, or lymphoid tissue can be present as soft tissue components related to the wall of the cyst.54 Differential diagnosis. A second branchial apparatus istula is the main differential consideration of thymic remnants. A second bran­ chial istula will pass between the internal and external carotid arteries and end in the superior tonsillar pillar, whereas a thymic cyst will pass posterior to the carotid bifurcation and terminate in the pyriform sinus.54 Additionally, about 50% of cervical thymic cysts extend into the superior mediastinum, and some can be seen in the inferior pole of the thyroid gland.8,104,146 Other differential considerations for a thymic cyst include a fourth branchial anomaly, TDC, thyroid/ parathyroid cyst, lymphatic malformation, cyst neuroblastoma, lymph­ adenopathy, external laryngocele, and vallecular cyst.54 Treatment. Treatment is surgical, and the prognosis is excellent if the resection is complete. There is a high recurrence rate with incom­ plete resection.22,98

Dermoid/Epidermoid Cyst Because of overlapping features, the terminology and classiication of dermoid, epidermoid, and teratoid cysts in the head and neck can lead to confusion.

Embryology. These masses are thought to arise from trapped epithe­ lial cell rests at the site of midline closure. Dermoids and epidermoids are ectodermal­lined inclusion cysts, and teratoids can contain tissues of all three germ­cell layers. Dermoids contain epithelial and dermal elements, whereas epidermoids contain only epithelial elements.54

Presentation. There is no gender predilection with dermoid and epidermoid cysts. Dermoid cysts of the neck commonly occur near the midline, with the most common location being the loor of the mouth, (11.5% of all dermoids), followed by other locations including the anterior neck, tongue, palate, and orbit.101,144,145 Epidermoid cysts are rarely found in the head and neck, and when they occur they usually present in infancy.191 Dermoid/epidermoid cysts become clinically apparent in the second or third decades of life, when they present as a painless, soft, slow­growing mass in the suprahyoid midline neck. The cyst can be variable in size, and rapid increase in size can be seen secondary to

B FIG 26-9 Thymic cyst. Axial (A) and coronal (B) contrast-enhanced CT images demonstrate a cystic mass (arrows) in the lateral infrahyoid neck at the level of the thyroid gland.

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PART II CT and MR Imaging of the Whole Body

association with a sinus tract, pregnancy, or increasing desquamation of skin appendage products.89,191,194 Masses lying in the sublingual space are often clinically inapparent and demonstrate minimal mass effect, but masses in the submandibular space present with a more obvious swelling or mass effect.89,215 Additionally, a distinguishing factor between TDCs and dermoid/epidermoid cysts are that whereas TDCs move with protrusion of the tongue, owing to their association with the hyoid bone, dermoid/epidermoid cysts are nonmobile with this maneuver.154 Dermoid cysts are well­deined encapsulated masses lined with squamous epithelium and may contain skin appendages in the form of sweat or sebaceous glands or hair follicles, which can lead to the formation of keratin and sebaceous material, including occasional hair. Epidermoid cysts lack skin appendages but have a histologic appear­ ance similar to dermoids.191 The incidence of malignant degeneration into squamous cell carcinoma is about 5% for dermoids.

The signal characteristics of this lesion can be confused with other cystic lesions such as an uncomplicated lymphatic malformation or ranula. It is important to accurately localize the lesions when they are located in the loor of the mouth. If the lesion is located above the mylohyoid muscle, it lies in the sublingual space and is amenable to an intraoral surgical approach. If it lies in the submandibular space, a submandibular approach would be used. The optimal imaging plane for localizing these masses into the appropriate space would be coronal CT or MRI.191

Teratoma Approximately 9% of all pediatric head and neck neoplasms are tera­ tomas, and less than 5% of all teratomas occur in the head and neck.38,99 In the pediatric population, most teratomas are extragonadal in loca­ tion, with 82% in the sacrococcygeal area; locations in the head and neck include neck, nasal cavity, paranasal sinus, oral cavity, orophar­ ynx, nasopharynx, temporal bone, ear, and orbit.7,112,201,202 Teratomas are thought to arise from misplaced pluripotential pri­ mordial germ cells and are classiied as true neoplasms because of their biological behavior with progressive and invasive growth patterns.170

Imaging Findings. On CT a dermoid cyst can appear as a thin­ walled unilocular mass with decreased attenuation and at times with CT attenuation values approximating that of fat (Fig. 26­10). Some­ times a virtually pathognomonic “sack­of­marbles” appearance, repre­ senting multiple small fatty nodules within the luid, is seen within the cyst. These cysts can also present with a more heterogeneous appear­ ance owing to differences in composition of the various skin append­ age components, including calciication. Thin peripheral enhancement can be seen following contrast administration.191 On MRI, signal changes vary depending on the composition of the various cyst components. T1 signal can be hyperintense due to lipid components or isointense to muscle, and T2 signal is usually hyperin­ tense to muscle. If calciication is present, this will cause low T2 signal. If a dermoid contains minimal complex elements, it can appear similar to an epidermoid. Postcontrast images may or may not demonstrate rim enhancement. T1 postcontrast fat­saturation images can be helpful to diagnose dermoids by assessing for signal dropout. Epidermoid cysts usually follow water signal, demonstrating homogenous low attenuation on CT and hypointense T1­weighted and hyperintense T2­weighted signal to muscle on MRI (Fig. 26­11).

Cervical Teratomas. Cervical teratomas are large and can present with extensive unilateral or more diffuse cervical swelling that can lead to obstetric complications such as dificult labor with malpresentation, premature labor, stillbirth, acute neonatal respiratory distress, and maternal polyhydramnios. The tumors that present later in life are smaller but have a higher incidence of malignancy.170 Embryology. Cervical teratomas can contain variable degrees of maturation, with mature elements derived from ectoderm, mesoderm, and endoderm and immature tissue mostly from neuroectoderm. Both mature and immature neuroectodermal elements tend to predominate in cervical teratomas.54 Imaging findings. On antenatal ultrasound, teratomas can appear well deined or iniltrative and demonstrate heterogeneous echo­ genicity with multiloculated areas of cystic and solid regions and acoustic shadowing from calciications on sonography.54,170

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FIG 26-10 Dermoid. A and B, Axial CT images demonstrate large fat-containing lesions (arrows) in the sublingual space.

CHAPTER 26

Imaging of the Head and Neck in the Pediatric Patient

763

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FIG 26-11 Epidermoid. A, Axial contrast-enhanced CT image demonstrates a nonenhancing midline lowdensity lesion (arrow) in the oral cavity, most consistent with an epidermoid. B, Sagittal T2-weighted fetal MRI demonstrates a T2 bright lesion (arrow) at the loor of the mouth.

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FIG 26-12 Teratoma. A, Lateral radiograph demonstrates a large soft tissue mass with calciications (arrow). Noncontrast coronal CT images in soft tissue (B) and bone windows (C) demonstrate a large soft tissue mass with calciications and fat (arrows).

On CT, the imaging characteristics will relect the pathologic makeup of the tumor. Most cervical teratomas are large, measuring up to 12 cm, and can appear primarily cystic, solid, or multicystic; about 50% contain calciication170,221 (Fig. 26­12). On MRI, the mass shows heterogeneous signal on all sequences and contains areas of T1 hyperintense signal in tissues containing fatty components and hypointense or hyperintense signal in areas of calciication.170,221 Vari­ able enhancement is seen after contrast administration. Because these tumors are large and can lead to airway compromise, intubation is often required.

Differential diagnosis. The primary differential diagnosis is lym­ phatic malformation, which more closely follows water signal on all pulse sequences. Because cervical teratoma can be dificult to distin­ guish from a lymphatic malformation with prenatal ultrasound, fetal MRI has been found to be helpful in such cases. Other differential considerations include cervical neuroblastoma (which can contain cal­ ciication), complicated TDC or branchial cleft cyst, goiter, hemangi­ oma, and external laryngocele.45 Treatment. For congenital cervical teratomas, surgery is manda­ tory and the mortality rate is 80% to 100% secondary to airway

764

PART II CT and MR Imaging of the Whole Body

complication. Therefore differentiating this tumor from other con­ genital space­occupying masses of the neck is important. The inci­ dence of true malignancy is less than 5%, and associated anomalies are uncommon. Prognosis with surgery is excellent.75,157

CONGENITAL MASSES OF THE NOSE Nasal Dermal Sinus Cyst Nasal dermal sinuses are thin epithelium­lined tubes that arise at exter­ nal ostia situated along the midline of the nose and extend deeply for a variable distance, extending sometimes to the intracranial compart­ ment. Nasal dermoid and epidermoid cysts are midline epithelium­ lined cysts and may coexist with dermal sinuses or present as isolated masses. Nasal dermal sinus cyst (NDSC) is the most common midline congenital lesion and accounts for 1% to 3% of all dermoids and 3.7% to 12.6% of all dermoids of the head and neck.151,161,162,175 Although most are sporadic, several familial cases have been reported.18,138 They can present at any age but are most commonly found in younger chil­ dren, with a mean age of presentation of 3 years. There is a male predilection, and these lesions are found anywhere between the gla­ bella and the base of the columella.161,162 About 56% present as midline cysts and 44% as midline sinus ostia.156

Embryology. Early in the embryo, the developing frontal bones are separated from the developing nasal bones by the fonticulus frontona­ salis.73,131,175 The nasal bones are separated from the cartilaginous nasal capsule by the prenasal space, which extends from the base of the brain to the nasal tip.131 The most accepted theory for the development of NDSC is the failure of involution of the anterior neuropore, with lack of regression of the diverticulum of dura that extends through the foramen cecum. The midline diverticula of dura normally project anteriorly into the fonticulus frontonasalis and anteroinferiorly into the prenasal space and touch the ectoderm. These diverticula usually regress before closure of the bone plates of the anterior skull base, but if the embryonic diverticula of dura become adherent to the supericial ectoderm, they may not regress normally and instead may pull ecto­

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derm with them as they retreat, creating a dermal/ectodermal tract that extends from the glabella through a canal at the frontonasal suture to the crista galli or beyond the crista to the interdural space between the two leaves of the falx.34,73,175 Depending on the contents and patency of the diverticulum, the resultant lesion can be a dermal sinus, dermoid cyst, nasal glioma, or encephalocele.83,156,229

Presentation. NDSC commonly presents as a painless cystic enlarge­ ment of any part of the nose, associated with one or more dimples.156 Externally, midline pits, fenestra, or discrete masses can be present, and they may be associated with hair protruding from the defect.18,21,88,175 With intermittent episodes of inlammation or discharge of sebaceous or inlammatory material there can be a variation in the size of the mass. Although there is no consistent associated pattern of malfor­ mation of the face and brain, an increased incidence of intracranial extension of the NDSC has been found in patients with multiple malformations.175,218 The extension of nasal dermoid cysts and dermal sinuses is variable, which may end blindly in the supericial tissues or extend both intra­ cranially and extracranially.175 The reported intracranial extension varies between 0% and 57%.131,151 Intracranial extension of the der­ moids is typically extraaxial, with extension usually occurring through the foramen cecum into the epidural space in the region of the crista galli (Fig. 26­13). When intracranial extension is present, signs and symptoms of meningitis or behavioral changes related to life­threatening frontal lobe abscess can be seen. Other complications include nasal abscess, periorbital­nasal cellulitis, osteomyelitis, cavernous sinus thrombosis, and seizures.151,175,218 Imaging Findings. Both CT and MRI are useful in evaluating the course of the sinus tract, cysts, and sequelae of infection. On CT, the course of a dermal sinus is seen as a well­deined gap between the nasal bones in the midline or in the frontal bone. An enlarged foramen cecum and biid­appearing or distorted crista galli are suggestive of but not pathognomonic for intracranial extension. These indings can present with or without intracranial extension or with intracranial

B FIG 26-13 Nasal dermoid. Axial (A) and sagittal (B) T1-weighted MRIs demonstrate a fat-containing lesion at the nasofrontal region, with intracranial extension (arrows).

CHAPTER 26

Imaging of the Head and Neck in the Pediatric Patient

765

extension of a ibrous cord without dermoid elements. The intracranial ends of dermoid cysts usually lie in a hollowed­out space along the anterior surface of a thickened enlarged crista galli. The ostium and tract usually appear as isodense ibrous channels or as lucent dermoid channels that can extend inward for variable distances. The bony canals indicate the course of the tract through the nasal bones, ossiied nasal septum, and skull base. On CT, noninfected dermoid cysts appear as nonenhancing masses of fat attenuation with an isodense rim to soft tissue. Stranding of the surrounding soft tissues and change in attenuation value of the cyst suggest secondary infection. An infected dermoid cyst has an appear­ ance similar to an abscess, with a peripheral rim of enhancement. A foramen cecum can be incompletely ossiied, a normal inding in chil­ dren younger than 1 year of age, appearing as a bony defect.54 In such cases, contrast administration can aid in the differentiation of enhanc­ ing cartilage in a young child from a nonenhancing true skull base defect, similar to differentiation of enhancing nasal mucosa from non­ enhancing dermoids.97,161,162 MRI is extremely valuable in assessing the intracranial and nasal components of these lesions. Thin­slice sagittal, coronal, and axial T1­weighted, T2­weighted with fat saturation, and fast­spin echo inversion recovery sequences should be obtained. Sagittal T1­weighted and inversion recovery sequences are best for demonstrating enlarge­ ment of the foramen cecum with intracranial extension, and postcon­ trast imaging with fat saturation has similar appearances as CT. Dermoid cysts commonly have close to fat signal as compared to brain on all sequences, with associated chemical shift artifact and suppres­ sion with fat saturation. Fibrous tracts demonstrate an isointense signal to brain on T1­weighted sequences.1

Presentation. Extranasal gliomas present in early infancy or child­ hood as irm, slightly elastic, reddish to bluish, skin­covered masses, and capillary telangiectasias may cover the lesion.180 They do not pulsate, do not increase in size with the Valsalva maneuver, and do not pulsate or swell following compression of the ipsilateral jugular vein.9,19,73 Intranasal gliomas lie within the nasal or nasopharyngeal cavities and present as large, irm, polypoid, submucosal masses that may extend inferiorly toward the nostril.73,187 They may protrude through the nostril and usually attach to the turbinates and come to lie medial to the middle turbinate between the middle turbinate and nasal septum.73 These can lead to obstruction of the nasal passage or blockage of the nasolacrimal duct, causing epiphora on the affected side. CSF rhinorrhea, meningitis, and epistaxis may be additional com­ plications and presenting complaints. Intranasal gliomas are commonly confused with inlammatory polyps, which usually lie medial to the middle turbinate, whereas inlammatory polyps typically lie inferolateral to the middle turbinate. Nasal gliomas usually present in infancy, whereas ordinary nasal polyps are rare in children younger than 5 years.199 Histologically, nasal gliomas resemble reactive gliosis rather than neoplasia and consist of large aggregates or small islands of glial tissue.33,199,225 Fibrous connective tissue enwraps the blood vessels and extends outward to form septa that divide the mass.187 Extranasal gliomas are surrounded by dermis, and intranasal gliomas are sur­ rounded by minor salivary glands, ibrovascular tissue, and nasal mucosa.73

Treatment. The nasal dermal sinuses are resected for three major

Imaging Findings. On imaging, nasal gliomas and encephaloceles

reasons: for cosmetic purposes, to avoid/treat complications of local infection, and to avoid/treat secondary complications such as second­ ary meningitis and cerebral abscess.167 To avoid unnecessary cranioto­ mies, surgical studies suggest that the best approach is to dissect the extracranial portion of the tract along its entire length from the super­ icial ostium to the extracranial surface of the enlarged foramen cecum and sever the tract at the extracranial end of the foramen cecum. Then send the severed end for pathologic examination, and if the specimen shows (epi)dermal elements at the foramen cecum, the dissection is extended intracranially. If no (epi)dermal elements are found at the foramen cecum, the procedure is concluded without intracranial exploration.102,175

appear as masses of soft tissue signal isointense to gray matter. The differentiation between a nasal glioma and an encephalocele is made based upon identiication of intracranial communication. If an intracranial communication is identiied, the mass is classiied as an encephalocele. This is best evaluated with MRI in the sagittal plane.54

Nasal Gliomas (Heterotopias) Nasal gliomas are congenital masses of glial tissue that may occur intranasally and/or extranasally at or near the root of the nose and may or may not be connected to the brain by a pedicle of glial tissue.160 They do not contain cerebrospinal luid (CSF)­illed space that is con­ nected with either of the CSF­containing spaces in the brain (ventricles or subarachnoid space). They are uncommon and account for only 4.5% of congenital nasal masses.175,180 They occur sporadically with no familial tendency and usually affect both genders equally.73 About 15% of patients with nasal heterotopias also manifest multiple cerebral heterotopias.225 Nasal gliomas are subclassiied into three types: extranasal (60%), intranasal (14%­30%), and mixed (10%­14%) forms. Extranasal gliomas lie external to the nasal bones and nasal cavities and typically occur at the bridge of the nose, to the left or right of the midline. Intranasal gliomas lie within the nasal or nasopharyngeal cavities. Mixed nasal gliomas consist of extranasal and intranasal components

and communicate via a defect in the nasal bones or around the lateral edges.137,225

Cephaloceles Cephaloceles are deined as herniations of intracranial contents through a cranial defect.141 When the herniation contains only menin­ ges, it is deined as a cranial meningocele, and if the herniation contains brain, then it is called a meningoencephalocele. They are classiied by the site of the cranial defect through which the brain and meninges herniate.141,185 Cephaloceles are common lesions, occurring in 1 per 4000 live births.17,103 The types of cephaloceles vary based on different populations. Sincipital cephaloceles are found in 1 in 35,000 live births in North America and Europe but are more common in Southeast Asia, where they are found in 1 per 5000 to 6000 live births.30,88 In Cauca­ sians, occipital cephaloceles are most common (67%­80%) whereas sincipital cephaloceles (2%­15%) and basal cephaloceles (10%) are uncommon.62,141 Sincipital encephaloceles commonly present in the neonatal or infantile period with a nasal mass or nasal stufiness, and nasopharyngeal basal cephaloceles present toward the end of the irst decade with mouth breathing or nasal stufiness.54

Anterior (Sincipital Cephaloceles). Anterior cephaloceles, also known as sincipital cephaloceles, are situated in the anterior part of the skull and include both interfrontal and frontoethmoidal cephalo­ celes.199 They always present as external masses along the nose, orbital margin, or forehead. With the interfrontal cephalocele, the cranial

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A

B

C

D

FIG 26-14 Anterior basal encephalocele. Axial T1-weighted (A) and coronal postcontrast (B) T1-weighted MRIs at the anterior skull base demonstrate a nonenhancing CSF-illed structure extending through a defect in the dura into the posterior ethmoid air cells and sphenoid sinus from the right middle cranial fossa (arrows). Sagittal T1-weighted (C) and axial T2-weighted (D) MRIs demonstrate a CSF signal lesion extending through a defect in the dura into the posterior ethmoid and sphenoid sinuses (arrows).

defect lies between two frontal bones and the cephalocele presents anteriorly as a midline mass between the defect. Frontoethmoid cephaloceles emerge outward from the skull defect at the junction of the frontal and ethmoid bones, immediately anterior to the crista galli. They are subclassiied into nasofrontal, nasoethmoidal, and nasoorbital subtypes based on the point at which the skull defect and hernia emerge externally. Various complications can occur depending on the size of the mass. For example, large masses stretch and thin the skin, obscure vision, block the airway, and may also cause pressure deformities of adjacent soft tissue and bone at the forehead, nose, and orbits, causing telecanthus or true bony hypertelorism.163,172

Basal Cephaloceles. Basal cephaloceles are subdivided into trans­ ethmoid, transsphenoidal, sphenoethmoid, and frontospenoid.54 The most common type is the sphenoethmoid type, and it usually presents as a pharyngeal mass with signs and symptoms of airway obstruction or CSF leak (Fig. 26­14). Other complications that can be seen with basal cephaloceles (transsphenoidal or sphenoethmoidal) include pituitary and hypothalamic dysfunction and decreased visual acuity secondary to herniation of the pituitary gland, hypothalamus, and optic apparatus into the sac.54 Embryogenesis. There is no universal agreement on the etiology of anterior cephalocele, but it is thought to be secondary to imperfect closure of the anterior neuropore of the neural tube at about the 25th

CHAPTER 26

Imaging of the Head and Neck in the Pediatric Patient

day of gestation. The basal cephaloceles, those related to the sphenoid bone, are thought to be secondary to persistence of the craniopharyn­ geal canal or failure of normal union of basilar ossiication centers.54,158 Histology. In a meningoencephalocele, the herniated neural tissue contains neurons with prominent astrogliosis, and the cyst wall is composed of glial and ibrous connective tissue without neurons.159 Imaging. CT is useful for imaging the bony margins of the skull base defect along with the soft tissue component of the lesion. MRI is the best imaging modality for evaluating the contents of the cephalo­ cele and in deining the cephalocele in relation to the pituitary stalk and gland as well as the position and state of the optic nerves, chiasm, and optic tracts.54

Nasopharyngeal Teratomas Head and neck nasopharyngeal teratomas are presumed to arise from primitive germ cells that get trapped in the normal migratory channel during development. They contain all three germ layers and arise from embryonic tissue that breaks off or fails to migrate to its normal des­ tination. More than 50% of nasopharyngeal teratomas are seen in the irst year of life and often arise from the superior or lateral wall of the nasopharynx. There is a female predilection for teratomas in the nasal cavity, and the typical clinical presentation is a neonate with severe respiratory distress, stridor, and dysphagia. CT and MRI are the best imaging modalities for teratomas, which can be identiied by the pres­ ence of fat and and calciication.200 Differential considerations for nasopharyngeal teratomas include dermoids, encephalocele, nasal glioma, rhabdomyosarcoma, hemangioma, lipoma, neuroibroma, and lymphoma.189

MALIGNANT NEOPLASMS Neoplasms of the head and neck comprise approximately 5% of all malignant neoplasms in the pediatric age group. Although lym­ phoma and rhabdomyosarcoma are the most common tumors, other tumors in this category include primary neuroblastoma, nasopharyn­ geal carcinoma (NPC), thyroid carcinoma, synovial sarcoma, and esthesioneuroblastoma.54,94

Lymphoma Lymphoreticular malignancies account for about 40% of all malignant disorders in children, with lymphoma representing 11% of pediatric malignancies and 50% of pediatric head and neck malignancies.54,213 It is the second most common malignancy in the head and neck in this age group and is equally divided between non­Hodgkin’s and Hodg­ kin’s lymphoma.54,82

Hodgkin’s Lymphoma. Hodgkin’s lymphoma represents 14% of all cases of lymphoma and has a bimodal age distribution: the irst peak in teenagers and young adults and the second peak in adults older than 40 years. The disease is uncommon in children younger than age 5, and there is a male predominance of 3 : 1 in the preteen years. Although the etiology remains unknown, there is a known association with Epstein­Barr virus in up to 50% of cases. There is also increased inci­ dence of the disease in patients with HIV, which carries a poorer prognosis. The disease is less common among Asian and African American populations.54 The majority of patients present with painless adenopathy, with 80% to 90% involving cervical lymph nodes. Some of the common constitutional symptoms include fever, night sweats, weight loss, anemia, fatigue, and pruritus.210 The tumor consists of malignant Reed­Sternberg cells and their mononuclear variants and normal reactive cells including lymphocytes

767

and eosinophils. Classic Hodgkin’s lymphoma represents 95% of cases and has been subclassiied into nodular sclerosing (60%­80%), mixed cellularity (15%­30%), lymphocyte predominant (5%), and lympho­ cyte depleted ( 2 months post injury). It likely represents a presyrinx state following disruption of normal transparenchymal CSF transit. A contributory role for cord tethering by adhesions has also been proposed, which may be amenable to intraoperative lysis.29 Chronic posttraumatic cord cysts or syringes (Fig. 28-36) are identiied as expansile structures that are isointense with CSF on all

CHAPTER 28

FIG 28-36 Posttraumatic syrinx. Sagittal T2-weighted MRI. Kyphotic deformity in the thoracic spine due to old compression fracture with posterior distraction. An extensive complex syrinx replaces the cord parenchyma proximal to the level of the injury. There is atrophy of the cord distally.

Spinal Trauma

821

and that are more sharply marginated compared with myelomalacia. Cord atrophy is a common inding in patients imaged more than 20 years after the initial trauma. Atrophy has been deined as an AP dimension of 7 mm or less in the cervical cord and 6 mm or less in the thoracic region.34,80 In 1982 Pang and Wilberger introduced the concept of spinal cord injury without radiographic abnormality (SCIWORA), originally described in the pediatric population as the presence of clinical indings (neurologic deicit) in the setting of normal x-rays and CT. The advent of MRI permitted characterization of the underlying spinal cord injury even when radiographs and CT scan were normal. In view of these advances, Pang reviewed his work in 2004 and advocated that only cases with neural injuries seen on MRI or those with normal MRI indings should be counted as SCIWORA, and purely extraneural compressive lesions should be excluded from the deinition of SCIWORA.74 Children diagnosed with SCIWORA but with normal MRI indings have shown more favorable clinical outcomes than those with cervical cord abnormalities on MRI.64 In adults with SCIWORA, parenchymal spinal cord injury is the single most important determinant in the long-term outcome. Cord hemorrhage has the worst prognosis, cord edema has the best. Longitudinal signal extension and associated extraneural injuries are also associated with poorer outcomes. Cases with purely neural injuries can be managed conservatively, but associated extraneural injuries, especially disk prolapse and ligamentous instability, warrant surgical management.92

THORACOLUMBAR FRACTURES IN PATIENTS WITH ANKYLOSING SPONDYLITIS TL fractures are signiicantly less common than cervical fractures in patients with AS (Fig 28-37). A majority of these fractures occur at the

A

B

C

FIG 28-37 Atypical injuries in patients with ankylosing spondylitis (AS). A, CT sagittal reformatted image of the thoracic spine. Retrolisthesis of the T8 vertebral body is due to disruption of the intervertebral disk and anterior and posterior longitudinal ligaments. There is also translation of the posterior elements. Note calciication of the anterior longitudinal ligament in this patient with AS. B and C, CT sagittal reformatted images of the cervical spine in a different patient. Widening of the C6-C7 disk with pseudoarthrosis of the facet joint (arrow) in a patient with AS.

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TL junction. Trent et al. originally classiied these fractures into three types: shearing injury (distractive lexion injury or distractive extension injury), wedge compression, or pseudarthrosis from chronic nonunion. Typically the shearing injuries are seen acutely; compression fractures generally have a chronic presentation, whereas pseudarthrosis can be seen subacutely after a missed fracture or in patients with microfractures leading to ibrosis. Most of these injuries are highly unstable and often require surgical treatment. The forces acting across the fracture site are drastically increased by the long lever arms of the fused thoracic and lumbar spine segments. This is further potentiated at the TL junction owing to the sheer weight of the thorax above.20

SACRAL INSUFFICIENCY FRACTURES Insuficiency fractures are a subtype of stress fracture that results from normal stress applied to abnormal bone that has lost its elastic resistance. Bone insuficiency is often the result of osteoporosis, metabolic bone disease, osseous metastatic disease, and marrow replacement. Sacral insuficiency fractures (SIFs) are a common cause of debilitating back pain in the elderly. Antecedent trauma is not identiied in two thirds of patients and when present is usually minor. The standard of care for the treatment of SIFs has been conservative management; more recently, sacroplasty has been advocated as an alternative to conservative therapy. SIFs most commonly involve the sacral ala lateral to the neural foramina and medial to the sacroiliac joints (zone 1). Fractures may be unilateral or bilateral and are reported with relatively equal frequency in the literature. There may also be a horizontal component to the fracture through the sacral bodies. This unique fracture pattern may be related to axial loading and weight bearing transmitted through the spine, resulting in sacral alar strain. Additionally, osteoporosis causes asymmetric loss of bony trabeculae in the sacral ala compared with the vertebral bodies, placing the lateral aspect of the sacrum at increased risk of insuficiency. On plain ilms SIFs appear as vertical bands of sclerosis oriented parallel to the sacroiliac joints. Cortical disruption and/or fracture lines may be evident. Occasionally fractures can have an aggressive appearance, simulating malignancy, with areas of sclerosis and periosteal reaction. Bone scintigraphy with technetium 99m–labeled methylenediphosphonate (99mTc MDP) is one of the most sensitive examinations for the detection of SIFs. Bone scintigraphy has a reported sensitivity of 96% for detection of SIFs, with a positive predictive value of 92%. Various patterns of radiotracer uptake have been described, with the so-called Honda sign, or H pattern, considered diagnostic of SIFs in the correct clinical setting. However, this pattern of radiopharmaceutical uptake is seen only in 20% to 40% of patients. Variations in the pattern of radiopharmaceutical activity in SIFs include uptake oriented unilaterally in the sacral ala, unilaterally with a horizontal strut, bilaterally without a horizontal strut, and as multiple foci of activity. Posterior planar images are the most sensitive (i.e., when the sacrum is closest to the detector). Follow-up scintigraphic results are quite variable, with changes in the radiopharmaceutical uptake pattern during a 10- to 33-month interval ranging from resolution of abnormal activity to no change or even worsening activity. CT may demonstrate sclerosis in the sacral ala and lateral sacrum paralleling the sacroiliac joints (Fig. 28-38) or fracture lines with or without bony callous. Coronal reformatted images are useful to detect the horizontal component. CT may also be useful to determine whether the fracture lines extend into the neural foramina, creating a potential pathway for cement if sacroplasty is being considered as a treatment option. CT is not as sensitive for detecting SIFs when compared with

FIG 28-38 Sacral insuficiency fracture. Axial CT image. Note the subtle lucencies oriented in the sagittal plane in the sacral ala (arrows) secondary to insuficiency fracture of the sacrum in this patient with unexplained back pain.

bone scintigraphy or MRI, with a reported sensitivity between 60% and 75%. MRI can detect early changes of sacral insuficiency and, similar to bone scintigraphy, has a reported sensitivity at or near 100%. Marrow edema is demonstrated as areas of increased signal intensity on T2-weighted and STIR images and low signal intensity on T1-weighted images. A hypointense fracture line is usually evident within the area of edema, although it is not seen in 7% of cases. Coronal oblique images in the plane of the sacrum better demonstrate the vertically oriented fractures and should be included in the imaging protocol if there is clinical suspicion. MRI can usually differentiate marrow edema secondary to SIFs from malignancy, with fat-saturation and postgadolinium imaging being particularly useful in this regard. Occasionally MRI can be confusing, especially if a fracture line is not evident, and correlative CT or follow-up imaging may be useful.61

CHRONIC CONDITIONS ATTRIBUTED TO TRAUMA OF THE THORACOLUMBAR SPINE Cord Herniation Spinal cord herniation is an unusual condition and can be deined as protrusion of the spinal cord beyond its dural sleeve. Patients present with variable symptoms or cord dysfunction, including Brown-Séquard syndrome and spastic paralysis. Although progression of neurologic deicits can sometimes be very slow, reduction of the spinal cord and repair of the defect are crucial in stopping or reversing neurologic deterioration.89 Congenital malformation of the meninges, trauma, and more recently trauma to the anterior surface of the thoracic dura by disk protrusions or osteophytes have been proposed as possible etiologies of spinal cord herniation.17 MRI indings of spinal cord herniation on axial images include protrusion through the dura in an anterolateral or anterior position. On sagittal images an anterior C-shaped kink of cord and secondary expansion of the dorsal subarachnoid space can be seen (Fig. 28-39). Cord deviation is generally limited to one or two thoracic spine

CHAPTER 28

Spinal Trauma

823

B

A

C

FIG 28-39 Cord herniation. A, Sagittal T2-weighted MRI of thoracic spine demonstrated anterior C-shaped kink of the cord and expansion of the posterior subarachnoid space. B and C, Axial images demonstrate anterior displacement and lattening of the cord (arrows).

segments. An extradural masslike area of signal intensity similar to that of the spinal cord may be observed occasionally and represents the herniated spinal cord. The dural defect occurs in the thoracic spine, most commonly between the levels of the T4 and T7 vertebrae. Associated cord atrophy and high T2 signal intensity may be observed within the thoracic cord. Occasionally scalloping of the vertebral body also may be seen.75

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CHAPTER 28 63. Magerl F, Aebi M, Gertzbein SD, et al: A comprehensive classiication of thoracic and lumbar injuries. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 3:184–201, 1994. 64. Mahajan P, Jaffe DM, Olsen CS, et al: Spinal cord injury without radiologic abnormality in children imaged with magnetic resonance imaging. J Trauma Acute Care Surg 75:843–847, 2013. 65. Marcon RM, Cristante AF, Teixeira WJ, et al: Fractures of the cervical spine. Clinics 68:1455–1461, 2013. 66. Reference deleted in proofs. Duplicate of Reference 65. 67. Mathen R, Inaba K, Munera F, et al: Prospective Evaluation of Multislice Computed Tomography Versus Plain Radiographic Cervical Spine Clearance in Trauma Patients. J Trauma-Inj Infect 62:1427–1431, 2007. 68. Michaleff ZA, Maher CG, Verhagen AP, et al: Accuracy of the Canadian C-spine rule and NEXUS to screen for clinically important cervical spine injury in patients following blunt trauma: A systematic review. CMAJ Can Med Assoc J J Assoc Medicale Can 184:E867–E876, 2012. 69. Miyanji F, Furlan JC, Aarabi B, et al: Acute Cervical Traumatic Spinal Cord Injury: MR Imaging Findings Correlated with Neurologic Outcome—Prospective Study with 100 Consecutive Patients. Radiology 243:820–827, 2007. 70. Mower WR, Hoffman JR, Pollack CV, et al For the NEXUS Group: Use of plain radiography to screen for cervical spine injuries. Ann Emerg Med 38:1–7, 2001. 71. Mueller FJ, Kinner B, Rosskopf M, et al: Incidence and outcome of atlanto-occipital dissociation at a level 1 trauma centre: A prospective study of ive cases within 5 years. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 22:65–71, 2013. 72. Müller CW, Otte D, Decker S, et al: Vertebral fractures in motor vehicle accidents—A medical and technical analysis of 33,015 injured front-seat occupants. Accid Anal Prev 66C:15–19, 2014. 73. Pal D, Sell P, Grevitt M: Type II odontoid fractures in the elderly: An evidence-based narrative review of management. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 20:195–204, 2011. 74. Pang D: Spinal cord injury without radiographic abnormality in children, 2 decades later. Neurosurgery 55:1325–1342, discussion 1342–1343, 2004. 75. Parmar H, Park P, Brahma B, et al: Imaging of Idiopathic Spinal Cord Herniation. Radiographics 28:511–518, 2008. 76. Patel AA, Dailey A, Brodke DS, et al: Thoracolumbar spine trauma classiication: The Thoracolumbar Injury Classiication and Severity Score system and case examples. J Neurosurg Spine 10:201–206, 2009. 77. Pintar FA, Yoganandan N, Maiman DJ, et al: Thoracolumbar Spine Fractures in Frontal Impact Crashes. Ann Adv Automot Med Annu Sci Conf 56:277–283, 2012. 78. Pitzen T, Lane C, Goertzen D, et al: Anterior cervical plate ixation: Biomechanical effectiveness as a function of posterior element injury. J Neurosurg 99:84–90, 2003. 79. Pizones J, Castillo E: Assessment of acute thoracolumbar fractures: Challenges in multidetector computed tomography and added value of emergency MRI. Semin Musculoskelet Radiol 17:389–395, 2013. 80. Potter K, Saifuddin A: Pictorial review: MRI of chronic spinal cord injury. Br J Radiol 76:347–352, 2003. 81. Pourtaheri S, Emami A, Sinha K, et al: The role of magnetic resonance imaging in acute cervical spine fractures. Spine J 2014. 180 degrees) has been termed generalized displacement or bulging disk. Bulging disks are not considered to be a form of herniation and are unlikely to result in clinical symptoms. A disk herniation is a localized disk displacement of disk material in the horizontal (axial) plane of less than 50% of of the disk circumference. A focal herniation is considered less than 25% of disk circumference, whereas a broad-based herniation is 25% to 50% of disk circumference. Distinction between disk protrusion and extrusion is based upon shape of the displaced material. Protrusion refers to a herniated disk in which the width of the displaced material in any plane does not exceed the width of its base (see Fig. 29-5A1-A3). In other words, the base against the parent disk is broader than any other diameter of the herniation. Furthermore, the displaced nuclear material is contained by some intact annular ibers and the posterior longitudinal ligament. An extruded disk suggests complete disruption of the outer annular ibers, with disk material entering the epidural space. Extrusions are characterized by herniated disk material demonstrating a distance greater than its base of origin (i.e., the base is narrower than any other diameter of the herniation) (see Fig. 29-6A1-A4). Disk herniations that have lost complete continuity with the disk of origin are characterized as sequestrations. Disk material displaced cranially or caudally from the site of extrusion, either remaining contiguous with the parent disk of origin or a sequestered fragment is known as migration (see Fig. 29-6B1-B4). Displaced disk material can be further classiied into anatomic zones in the axial plane.28 The central zone, deined by the medial margin of the facets; the subarticular zone (lateral recess), deined as the medial facet margin to the medial pedicle margin; the foraminal zone, deined as the medial pedicle margin to the lateral pedicle margin; and the extraforaminal zone, which is deined as peripheral to the lateral pedicle margin. Over 90% of lumbar disk herniations occur at the L4-L5 level, with most occurring posterolaterally.94 Therefore most disk herniations affect the traversing roots within the lateral recess. For example, a posterolateral disk herniation at L5-S1 would contact/impinge upon the traversing S1 root and result in S1 radiculopathy (see Fig. 29-6C1-C3). Compromise of the exiting L4 nerve at the level of the L4-L5 disk level would be due to cephalad migration

of extruded disk material or disk displacement into the L4-L5 neural foramen (see Fig. 29-6D1-D2). Careful attention to the descriptions of disk herniation characterization and location, as well as imaging evaluation with knowledge of the presenting clinical context, allows for more accurate assessment, reporting, and interpretation of disk disease for the individual patient.

CERVICAL SPINE Although neck pain and cervical radiculopathy are commonly seen in clinical practice, recent studies have concluded that imaging may be overutilized.34 Similar to patients presenting with low back pain, physicians encountering the patient with neck pain are confronted with a diagnostic dilemma and the role of imaging. Multiple studies have concluded an association between previous injury and the development of neck pain, but they have also suggested that causation is likely multifactorial, including psychological, social, and stress-related factors.8,34,43,59,76,108 Chronic pain may also be seen in postoperative patients, as well as those presenting with ossiication of the posterior longitudinal ligament. As in the lumbar spine, age-related changes in the cervical spine are common, asymptomatic, and increase with age. Likewise there is a basic speciicity fault in cervical spine imaging that spondylosis, central canal stenosis and foraminal narrowing, and facet changes are ubiquitous in asymptomatic patients.37,38,62-64,79,107

Anatomy The cervical spine consists of seven vertebral bodies with three articulations, including the diskovertebral complex, zygapophyseal joints, and the uncovertebral joints. Anatomically the cervical uncovertebral joints, or joints of Luschka, are formed by the paired uncinate process, bony ridges directed superiorly and posteriorly from the posterolateral margin of the vertebral bodies, which articulate with notches along the posterolateral surfaces of the adjacent vertebral inferior end plate. The neural foramina are bordered anteromedially by the uncinate processes and posterolaterally by the facet joints, with the pedicles of adjacent vertebral bodies forming the superior and inferior borders. The cervical zygapophyseal joints are more obliquely oriented and share equally in bearing axial compressive loads with the intervertebral disks11 (Fig. 29-7).

Imaging of Cervical Degenerative Disk Disease Pathophysiology. Analogous to lumbar disk herniations, the natural history of cervical disk herniation is spontaneous regression, with extrusions, migrated or sequestered material, and laterally oriented disk herniations more likely to undergo resolution.14,28,66 However, in the cervical spine, compressive lesions are more likely to have an osseous component rather than soft disk material, thus resolution is less likely compared to the lumbar spine. Osteophyte formation or squaring of the uncinate processes, as well as facet arthropathy and disk space height loss, all contribute to foraminal narrowing, resulting in cervical radicular symptoms (Fig. 29-8). The exiting cervical nerve roots travel along an inferior course through the foramen at about 45 degrees with respect to the coronal plane. Cervical nerves exit above the level of their respective disk level until C8, where is there is a transition to the nerves exiting below their respective disk level. Hence a foraminal extrusion compromising the C4-C5 foramen would impinge upon the exiting C5 nerve root, whereas a paracentral disk extrusion at C4-C5 will contact the traversing C6 nerve root. The most commonly affected levels are C5-C6 and C6-C7. Cervical intervertebral disks are structurally different than lumbar disks. Compared to lumbar intervertebral disks, the cervical disk

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C FIG 29-7 Normal cervical anatomy. A, Sagittal T2-weighted fat suppression image demonstrates hyperintense T2 CSF, as well as inclusion of the cerebellar tonsils and upper thoracic levels. B, Axial gradient echo image at the level of the intervertebral disk (D) demonstrates the anterior and posterior divisions of the exiting nerve roots (arrows), as well as the posterolaterally positioned uncovertebral joints of Luschka (*). C, Corresponding axial CT image shows the paired facet joints (V).

anulus is not completely concentric, diminutive posteriorly and thicker anteriorly, functioning as an interosseous ligament rather than a constraint.11,65 The small nuclear component disappears early in life, leaving a residual ibrocartilage plate, leading to internal cracks, issures, and increased mechanical stresses across the cartilaginous end plates, resulting in slowly developing disk-osteophyte complexes encroaching on the ventral canal and neural foramina. Increased loading of the uncovertebral joints results in hypertrophic change, compromising the lateral recesses and neural foramen. Changes occurring in the anterior column place increased stress across the facet joints, also resulting in hypertrophy and ligamentum lavum buckling anteriorly,63 further narrowing the central canal. Other than static

compression of the cervical cord, dynamic changes occurring during lexion and extension contribute to repetitive cord injury. During lexion, the spinal cord lengthens, allowing for contact along ventrally positioned osteophytes, whereas extension causes increased anterior lavum buckling and thus narrowing of the canal posteriorly.63,71,115 A central disk herniation/disk-osteophyte complex can encroach upon the ventral thecal sac and eventually progress to cord compression and cervical spondyolytic myelopathy (Fig. 29-9). In patients with neurologic symptoms, MRI readily depicts myelopathic changes in the cervical cord. Focal intramedullary T2 hyperintensity and corresponding T1 hypointensity may represent irreversible myelomalacia, including demyelination, gliosis, and cystic necrosis,2,63,77,88,95,105,106 whereas a

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C FIG 29-8 Cervical disk-osteophyte complex. A, Sagittal T2-weighted image shows subchondral end-plate edema at C3-C4, with an associated posterior disk-osteophyte complex (arrow). The axial T2 (B) and T2* (C) images show the central and left paracentral posterior disk-osteophyte complex to efface the ventral thecal sac, as well as narrowing of the left lateral recess and neural foramen due to uncovertebral joint hypertrophy.

more faint-appearing or indistinct T2 hyperintensity is more likely to relect reversible edema.60,63,95 Moreover, gadolinium enhancement20,63,82 and T1 hypointensity has been shown to be a poor prognostic indicator for recovery following decompression.2,5,32,60,70,74,102,104 Lastly, recent work evaluating diffusion tensor imaging has shown that reduced fractional anisotropy values relect symptomatic myelopathy regardless of the presence of T2 hyperintensity and thus may prove more sensitive in identifying symptomatic and asymptomatic patients.13,46,47 In patients presenting with cervical radiculopathy, the North American Spine Society (2010) currently recommends that MRI be performed as the initial imaging modality. However, CT myelography may

be performed in patient populations with contraindications to MRI or in those situations where determining the nature of the compressive lesion—osseous versus disk as the cause of the symptoms (Fig. 29-10)—might perhaps alter the operative management.

THORACIC DISK DISEASE Degenerative disk disease of the thoracic spine is less common than both cervical and lumbar spine disease.109 Accurate diagnosis of thoracic spine pathology requires not only a strong clinical suspicion but also appropriate diagnostic imaging examinations. Operations

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FIG 29-9 Cervical disk herniation with severe stenosis. Sagittal (A) and axial (B) T2-weighted images show a large central disk extrusion arising from C5-C6, with cranial and caudal migration (arrows) effacing the ventral thecal sac and compressing the spinal cord. The sagittal image also shows focal hyperintense T2 signal within the cord (long arrow in A), compatible with contusion/myelomalacia.

resulting from symptomatic disk herniations in the thoracic spine constitute less than 1% to 2% of all disk surgeries.28,56,101 It has been estimated that the incidence of symptomatic disk herniations of the thoracic spine occur in about 1 in 1 million persons per year,18,109 resulting an incidence of approximately 0.25% to 0.75% each year. The occurrence in symptomatic herniations is greatest between the fourth and sixth decades of life, with peak incidence in the ifth decade. There is a slight male predominance, with symptomatic females presenting later in life. Symptomatic disk herniations may be seen in adolescents as well, typically in patients with Scheuermann’s disease. Similar to lumbar and cervical disk herniations, Wood and colleagues concluded that thoracic spine disk herniations rarely change over time or become symptomatic.114 Symptomatic thoracic spinal canal stenosis related to aging is less common compared to the cervical and lumbar spine, likely owing to the added stability of the thoracic cage, and when present more commonly affects the lower thoracic spine.63

Anatomy When compared with the cervical and lumbar spine, the thoracic spine is relatively rigid because of the thoracic rib cage. The facets of the T1 through T10 vertebral bodies are vertically oriented, with a slight medial angulation in the coronal plane. As a result of the orientation of these facets, the thoracic spine has signiicant stability during lexion and extension and allows greater movement in both rotational and lateral bending movements. Studies have shown that biomechanically the intervertebral disks of the thoracic spine are at greatest risk for injury when there is a combined torsion and bending force.109 The spinal canal has a circular morphology, and despite the cord having the smallest diameter in the thoracic spine, the thoracic cordto-canal ratio is 40% compared with 25% in the cervical spine.109 The

dentate ligament runs longitudinally between the spinal cord and nerve roots, limiting posterior displacement of the cord within the canal, thus placing the cord at increased risk for ventral compression due to an anterior disk or bony processes. Additionally the natural kyphosis of the thoracic spine causes the cord to rest directly on the posterior longitudinal ligament and posterior aspect of the diskovertebral complex.

Imaging of Thoracic Degenerative Disk Disease Pathophysiology. As commonly seen in the cervical and lumbar regions, a higher percentage of disk herniations occur in a central or paracentral location, thus causing myelopathic symptoms.109 The majority of symptomatic disk herniations involve the middle to lower thoracic spine, with most surgical interventions occurring between T9 and T1128,103 and 7% of these herniations resulting in intradural extension. Thoracic disk herniations may be calciied, which may cause adhesion between the disk fragment and dura,40,91 and previous thoracic spine surgery may contribute to intradural fragments.26 Of note, herniations at the level of the conus or high cauda equina can mimic lumbar disease symptoms, and thus all lumbar MRI studies must include the conus.28,58 Initial radiographs are useful in deining alignment, acute osseous injuries, and detecting intradiskal calciications. Intervertebral disk calciications are often identiied in symptomatic thoracic disk herniations, ranging from 45% to 71%, but are only identiied in 10% of asymptomatic herniations.93,109 CT myelography can accurately diagnose disk herniations and associated osseous pathology (Fig. 29-11). On MRI T1-weighted images, disk herniations appear as intermediate signal, and on T2-weighted images as low signal. A pseudomyelogram appearance is seen on T2-weighted images secondary to the surrounding CSF. Calciications within the disk appear as low signal on both T1 and T2 images.

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D FIG 29-10 Severe acquired cervical spinal stenosis. Axial (A, B) and sagittal (C) reformatted images from a CT myelogram demonstrate a large central disk extrusion at C4-C5 (arrows) causing severe cord compression. D, Axial CT image through the C6-C7 level shows a partially calciied disk-osteophyte complex, with uncovertebral joint hypertrophy severely narrowing the foramen and impinging upon the exiting right C7 nerve root.

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FIG 29-11 Thoracic disk herniation. Sagittal (A) and axial (B) reformatted images from a CT myelogram show multilevel disk bulges, with a focal right paracentral disk protrusion at T5-T6 (arrow). Note vacuum disk phenomenon and Schmorl’s nodes at multiple thoracic levels.

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26. D’Andrea G, Trillo G, Roperto R, et al: Intradural lumbar disc herniations: The role of MRI in preoperative diagnosis and review of the literature. Neurosurg Rev 27(2):75–80, discussion 81–82, 2004. 27. Patel ND, Broderick DF, Burns J, et al: ACR Appropriateness Criteria® Low Back Pain. Available at https://acsearch.acr.org/docs/69483/ Narrative/. American College of Radiology. Accessed January 16, 2016. 28. Del Grande F, Maus TP, Carrino JA: Imaging the intervertebral disk: Age-related changes, herniations, and radicular pain. Radiol Clin North Am 50(4):629–649, 2012. 29. Deyo RA, Weinstein JN: Low back pain. N Engl J Med 344:363–370, 2001. 30. Elias F: Roentgen indings in the asymptomatic cervical spine. N Y State J Med 58:3300–3303, 1958. 31. Fardon DF, Milette PC: Combined Task Forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Nomenclature and classiication of lumbar disc pathology. Recommendations of the Combined Task Forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine (Phila Pa 1976) 26(5):E93–E113, 2001. 32. Fernandez de Rota JJ, Meschian S, Fernandez de Rota A, et al: Cervical spondylotic myelopathy due to chronic compression: The role of signal intensity changes in magnetic resonance images. J Neurosurg Spine 6:17–22, 2007. 33. Feydy A, Pluot E, Guerini H, et al: Osteoarthritis of the wrist and hand, and spine. Radiol Clin North Am 47(4):723–759, 2009. 34. Goode AP, Freburger J, Carey T: Prevalence, practice patterns, and evidence for chronic neck pain. Arthritis Care Res (Hoboken) 62(11):1594–1601, 2010. 35. Gore DR, Sepic SB, Gardner GM: Roentgenographic indings of the cervical spine in asymptomatic people. Spine 1:521–524, 1986. 36. Hammouri QM, Haims AH, et al: The utility of dynamic lexionextension radiographs in the initial evaluation of the degenerative lumbar spine. Spine (Phila Pa 1976) 32(21):2361–2364, 2007. 37. Hayashi H, Okada K, Hamada M, et al: Etiologic factors of myelopathy. A radiographic evaluation of the aging changes in the cervical spine. Clin Orthop Relat Res 214:200–209, 1987. 38. Heller CA, Stanley P, Lewis-Jones B, et al: Value of x-ray examinations of the cervical spine. Br Med J 287:1276–1278, 1983. 39. Jacobs DS: Degenerative diseases of the spine. Haaga: CT and MRI of the Whole Body, ed 5, St. Louis, 2008, Mosby, pp 755–799. 40. Jenkins LE, Bowman M, Cotler HB, et al: Intradural herniation of a lumbar intervertebral disc. J Spinal Disord 2(3):196–200, 1989. 41. Jensen MC, Brant-Zawadzki MN, Obuchowski N, et al: Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med 331:69–73, 1994. 42. Jinkins JR: Acquired degenerative changes of the intervertebral segments at and suprajacent to the lumbosacral junction. A radioanatomic analysis of the nondiscal structures of the spinal column and perispinal soft tissues. Eur J Radiol 50(2):134–158, 2004. 43. Kaaria S, Laaksonen M, Rahkonen O, et al: Risk factors of chronic neck pain: A prospective study among middle-aged employees. Eur J Pain 16(6):911–920, 2012. 44. Kalichman L, Li L, Kim DH, et al: Facet joint osteoarthritis and low back pain in the community-based population. Spine 33:2560–2565, 2008. 45. Kang C, Kim Y, Lee S, et al: Can magnetic resonance imaging accurately predict concordant pain provocation during provocative disc injection? Skeletal Radiol 38:877–885, 2009. 46. Kara B, Celik A, Karadereler S, et al: The role of DTI in early detection of cervical spondylotic myelopathy: A preliminary study with 3-T MRI. Neuroradiology 53(8):609–616, 2011. 47. Keřkovský M, Bednařík J, Dušek L, et al: Magnetic resonance diffusion tensor imaging in patients with cervical spondylotic spinal cord compression: Correlations between clinical and electrophysiological indings. Spine (Phila Pa 1976) 37(1):48–56, 2012. 48. Khalil JG, Nassr A, Maus TP: Physiologic imaging of the spine. Radiol Clin North Am 50(4):599–611, 2012.

49. Kjaer P, Leboeuf C, Korsholm L, et al: Magnetic resonance imaging and low back pain in adults: A diagnostic imaging study of 40-year-old men and women. Spine 30:1173–1180, 2005. 50. Kotsenas AL: Imaging of posterior element axial pain generators: Facet joints, pedicles, spinous processes, sacroiliac joints, and transitional segments. Radiol Clin North Am 50(4):705–730, 2012. 51. Kuisma M, Karppinen J, Niinimaki J, et al: A three-year follow-up of lumbar spine endplate (Modic) changes. Spine (Phila Pa 1976) 31(15):1714–1718, 2006. 52. Kuisma M, Karppinen J, Niinimaki J, et al: Modic changes in endplates of lumbar vertebral bodies: Prevalence and association with low back and sciatic pain among middle-aged male workers. Spine (Phila Pa 1976) 32(10):1116–1122, 2007. 53. Kulisch SD, Ulstrom CL, Michael CJ: The tissue origin of low-back pain and sciatica: A report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. Orthop Clin North Am 22:181–187, 1991. 54. Lam KS, Carlin D, Mulholland RC: Lumbar disc high-intensity zone (The value and signiicance of provocative discography in the determination of the discogenic pain source). Eur Spine J 9:36–41, 2000. 55. Lee MJ, Riew DK: The prevalence cervical facet arthrosis: An osseous study in a cadaveric population. Spine J 9:711–714, 2009. 56. Levi N, Gjerris F, Dons K: Thoracic disc herniation: Unilateral transpedicular approach in 35 consecutive patients. J Neurosurg Sci 43:37–42, 1999. 57. Luoma K, Vehmas T, Grönblad M, et al: Relationship of Modic type 1 change with disk degeneration: A prospective MRI study. Skeletal Radiol 38:237–244, 2009. 58. Lyu RK, Chang HS, Tang LM, et al: Thoracic disc herniation mimicking acute lumbar disc disease. Spine 24:416–418, 1999. 59. Makela M, Heliovaara M, Sievers K, et al: Prevalence, determinants, and consequences of chronic neck pain in Finland. Am J Epidemiol 134(11):1356–1367, 1991. 60. Mastronardi L, Elsawaf A, Roperto R, et al: Prognostic relevance of the post operative evolution of intramedullary spinal cord changes in signal intensity on magnetic resonance imaging after anterior decompression for cervical spondylotic myelopathy. J Neurosurg Spine 7(6):615–622, 2007. 61. Masui T, Yukawa Y, Nakamura S, et al: Natural history of patients with lumbar disc herniation observed by magnetic resonance imaging for minimum 7 years. J Spinal Disord Tech 18(2):121–126, 2005. 62. Matsumoto M, Fujimura Y, Suzuki N, et al: MRI of cervical intervertebral discs in asymptomatic subjects. J Bone Joint Surg Br 80(1):19–24, 1998. 63. Maus TP: Imaging of spinal stenosis: Neurogenic intermittent claudication and cervical spondylotic myelopathy. Radiol Clin North Am 50(4):651–679, 2012. 64. Maus TP, Aprill CN: Lumbar diskogenic pain, provocation diskography, and imaging correlates. Radiol Clin North Am 50(4):681–704, 2012. 65. Mercer S, Bogduk N: The ligaments and anulus ibrosus of human adult cervical intervertebral discs. Spine 24:619–626, 1999. 66. Mochida K, Komori H, Okawa A, et al: Regression of cervical disc herniation observed on magnetic resonance images. Spine 23:990–997, 1998. 67. Modic MT, Obuchowski NA, Ross JS, et al: Acute low back pain and radiculopathy: MR imaging indings and their prognostic role and effect on outcome. Radiology 237(2):597–604, 2005. 68. Modic MT, Steinberg PM, Ross JS, et al: Degenerative disk disease (Assessment of changes in vertebral body marrow with MR imaging). Radiology 166:193–199, 1988. 69. Monument MJ, Salo PT: Spontaneous regression of a lumbar disk herniation. CMAJ 183(7):823, 2011. 70. Morio Y, Teshima R, Nagashima H, et al: Correlation between operative outcomes of cervical compression myelography and MRI of the spinal cord. Spine 26(11):123, 2001. 71. Muhle C, Weinert D, Falliner A, et al: Dynamic changes of the spinal canal in patients with cervical spondylosis at lexion and extension using magnetic resonance imaging. Invest Radiol 33(8):444–449, 1998.

CHAPTER 29 72. Mulleman D, Mammou S, Griffoul I, et al: Pathophysiology of disk-related sciatica. I.–Evidence supporting a chemical component. Joint Bone Spine 73(2):151–158, 2006. 73. Mulleman D, Mammou S, Griffoul I, et al: Pathophysiology of diskrelated low back pain and sciatica. II. Evidence supporting treatment with TNF-alpha antagonists. Joint Bone Spine 73(3):270–277, 2006. 74. Mummaneni PV, Kaiser MG, Matz PG, et al: Preoperative patient selection with magnetic resonance imaging, computed tomography, and electroencephalography: Does the test predict outcome after cervical surgery? J Neurosurg Spine 11(2):119–129, 2009. 75. Newman JS, Weissman BN, Angevine PD, et al: ACR Appropriateness Criteria® Chronic Neck Pain. Available at https://acsearch.acr.org/ docs/69426/Narrative/. American College of Radiology. Accessed February 22, 2014. 76. Nolet PS, Cote P, Cassidy JD, et al: The association between a lifetime history of a neck injury in a motor vehicle collision and future neck pain: A population-based cohort study. Eur Spine J 19(6):972–981, 2010. 77. Ohshiro I, Hatayama A, Kaneda K, et al: Correlation between histopathologic features and magnetic resonance images of spinal cord lesions. Spine 18:1140–1149, 1993. 78. Ohtori S, Inoue G, Ito K, et al: Tumor necrosis factor-immunoreactive cells and PGP 9.5-immunoreactive nerve ibers in vertebral endplates of patients with discogenic low back pain and Modic type 1 or type 2 changes on MRI. Spine 31(9):1026–1031, 2006. 79. Okada E, Matsumoto M, Fujiwara H, et al: Disc degeneration of cervical spine on MRI in patients with lumbar disc herniation: Comparison study with asymptomatic volunteers. Eur Spine J 20(4):585–591, 2011. 80. Olmarker K, Rydevik B, Nordborg C: Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 18:1425–1432, 1993. 81. O’Neill C, Kurganshy M, Kaiser J, et al: Accuracy of MRI for diagnosis of discogenic pain. Pain Physician 11:311–326, 2008. 82. Ozawa H, Sato T, Hyodo H, et al: Clinical signiicance of intramedullary Gd-DTPA enhancement in cervical myelopathy. Spinal Cord 48(5):415–422, 2010. 83. Peng B, Hao J, Hou S, et al: Possible pathogenesis of painful intervertebral disc degeneration. Spine 31:560–566, 2006. 84. Peng B, Hou S, Wu W: The pathogenesis and clinical signiicance of a high-intensity zone (HIZ) of lumbar intervertebral disc on MRI imaging in the patient with discogenic low back pain. Eur Spine J 15(5):583–587, 2006. 85. Peng B, Wu W, Hou S, et al: The pathogenesis of discogenic low back pain. J Bone Joint Surg Br 87:62–67, 2005. 86. Pengel LH, Herbert RD, Maher CG, et al: Acute low back pain: Systematic review of its prognosis. BMJ 327:323–327, 2003. 87. Rahme R, Moussa R: The Modic vertebral end plate and marrow changes: Pathologic signiicance and relation to low back pain and segmental instability of the lumbar spine. Am J Neuroradiol 29(5): 838–842, 2008. 88. Ramanauskas WL, Wilner HI, Metes JJ, et al: MR imaging of compressive myelomalacia. J Comput Assist Tomogr 13:399–404, 1989. 89. Rankine JJ, Gill KP, Hutchinson CE, et al: The clinical signiicance of the high-intensity zone on lumbar spine magnetic resonance imaging. Spine 24:1913–1919, 1999. 90. Rannou F, Ouanes W, Boutron I, et al: High-sensitivity C-reactive protein in chronic low back pain with vertebral end-plate Modic signal changes. Arthritis Rheum 57:1311–1315, 2007. 91. Reema C, Prabodhan P, Kshitij C, et al: MRI Diagnosis of intradural lumbar disc herniation. Report of three cases with review of literature. Internet J Orthop Surg 18:2, 2010. Available at http://ispub.com/IJOS/ 18/2/6425. Accessed March 8, 2014. 92. Ricketson R, Simmons JW, Hauser BO: The prolapsed intervertebral disc (The high-intensity zone with discography correlation). Spine 21:2758–2762, 1996. 93. Rogers MA, Crockard HA: Surgical treatment of the symptomatic herniated thoracic disk. Clin Orthop Relat Res 300:70–78, 1994.

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94. Ross JS, Brant-Zawadzki M, Moore KR, et al: Diagnostic imaging spine, Salt Lake City, 2007, Amirys. 95. Saifuddin A, Braithwaite I, White J, et al: The value of lumbar spine magnetic resonance imaging in the demonstration of anular tears. Spine 23:453–457, 1998. 96. Savage RA, Whitehouse GH, Roberts N: The relationship between the magnetic resonance imaging appearance of the lumbar spine and low back pain, age and occupation in males. Eur Spine J 6:106–114, 1997. 97. Schellhas KP, Pollei SR, Gundry CR, et al: Lumbar disc high-intensity zone (Correlation of magnetic resonance imaging and discography). Spine 21:79–86, 1996. 98. Schonstron NR, Hansson GH: Thickness of the lumbar ligamentum lavum as a function of load: An in vitro experimental study. Clin Biomech 6:19–24, 1991. 99. Schwarzer AC, Wang S, O’Driscoll D, et al: The ability of computed tomography to identify a painful zygapophysial joint in patients with chronic low back pain. Spine 20:907–912, 1995. 100. Siebert E, Prüss H, Klingebiel R, et al: Lumbar spinal stenosis: Syndrome, diagnostics and treatments. Nat Rev Neurol 5:392–403, 2009. 101. Singounas EG, Kypriades EM, Kellerman AJ, et al: Thoracic disc herniation analysis of 14 cases and review of the literature. Acta Neurochir (Wien) 116(1):49–52, 1992. 102. Smith ZA, Buchanon CC, Raphael D, et al: Ossiication of the posterior longitudinal ligament: Pathogenesis, management, and current surgical approaches. A review. Neurosurg Focus 30(3):E10, 2011. 103. Stillerman CB, Chen TC, Douldwell WE, et al: Experience in the surgical management of 82 symptomatic herniated thoracic discs and review of the literature. J Neurosurg 88:623–633, 1998. 104. Suri A, Chabbra RP, Mehta VS, et al: Effect of intramedullary signal changes on the surgical outcome of patients with cervical spondylotic myelopathy. Spine J 3(1):33–45, 2003. 105. Takahashi M, Yamashita Y, Sakamoto Y, et al: Chronic cervical cord compression: Clinical signiicance of increased signal intensity on MR imaging. Radiology 173:219–224, 1989. 106. Taneichi H, Abumi K, Kaneda K, et al: Monitoring the evaluation of intramedullary lesions in cervical spinal cord injury. Qualitative and quantitative analysis with sequential MR imaging. Paraplegia 32:9–18, 1994. 107. Teresi LM, Lufkin RB, Reicher MA, et al: Asymptomatic degenerative disk disease and spondylosis of the cervical spine: MR imaging. Radiology 164(1):83–88, 1987. 108. van der Donk J, Schouten JS, Passchier J, et al: The associations of neck pain with radiological abnormalities of the cervical spine and personality traits in a general population. J Rheumatol 18(12):1884– 1889, 1991. 109. Vanichkachorn JS, Vaccaro AR: Thoracic disk disease: Diagnosis and treatment. J Am Acad Orthop Surg 8:159–169, 2000. 110. Van Rijn JC, Klemetso N, Reitsma JB, et al: Observer variation in the evaluation of lumbar herniated discs and root compression: Spiral CT compared with MRI. Br J Radiol 79:372–377, 2006. 111. Videman T, Battié MC, Gill K, et al: Magnetic resonance imaging indings and their relationships in the thoracic and lumbar spine. Insights into the etiopathogenesis of spinal degeneration. Spine 2:928–935, 1995. 112. Vroomen P, de Krom M, Knottnerus J: Predicting the outcome of sciatica at short-term follow-up. Br J Gen Pract 52:119–123, 2002. 113. Wang Y, Videman T, Battle MC: Modic changes: Prevalence, distribution patterns, and association with age in white men. Spine J 12(5):411–416, 2012. 114. Wood KB, Blair JM, Aepple DM, et al: The natural history of asymptomatic thoracic disc herniations. Spine 22(5):525–529, 1997. 115. Zhang L, Zeitoun D, Rangel A, et al: Preoperative evaluation of the cervical spondylotic myelopathy with lexion-extension magnetic resonance imaging: About a prospective study of ifty patients. Spine (Phila Pa 1976) 36(17):E1134–E1139, 2011.

30 Spinal Tumors Fanny E. Morón, Alfred Delumpa, and Janio Szklaruk

INTRODUCTION Spinal neoplasms are divided into three groups based on their anatomic locations: extradural, extramedullary-intradural, and intramedullary tumors (Fig. 30-1). Extradural tumors include masses in the bones, disks, and paraspinal soft tissues. The majority of spinal tumors (60%) in adults are extradural tumors and are most commonly (90%) metastases of systemic cancer.62 Extramedullary-intradural tumors include masses originating from the dura/arachnoid and nerves. They are the second most common spinal tumors in adults (20%-30%) and most are either meningioma (50%) or peripheral nerve sheath tumors (50%).14 Intramedullary spinal cord tumors (IMSCTs) occur within the spinal cord. IMSCTs are the least common spinal tumor type in adults (4%-10%) but the most common spinal tumors in children (35%).14,79 IMSCTs primarily consist of gliomas (90%), of which ependymomas represent 60% and astrocytomas 30%14 (Fig. 30-2). Even though rare, IMSCTs are usually associated with signiicant neurologic dysfunction, morbidity, and mortality. The clinical presentation for spinal cord tumors often includes back pain, weakness, and/or insidious and progressive myelopathy. Torticollis and scoliosis can be seen in younger children. Patients with symptomatic spinal cord tumors often undergo a computed tomography (CT) examination of the spine as the irst imaging modality. These images should be evaluated for the presence of intramedullary or epidural hyperdensity, which is always abnormal, usually relecting trauma, neoplasm, or vascular malformation. Additionally CT helps identify matrix calciications and extent of osseous destruction in cases of extradural tumors. However, magnetic resonance imaging (MRI) is the most appropriate imaging modality for any spinal cord and extramedullary-intradural pathology and for most of the extradural lesions.61 The contrast resolution of MRI is useful in identifying the anatomic location and soft tissue extent of all spinal tumors. Management and treatment of these tumors is highly dependent on the clinical presentation, tumor location, and histology. In this chapter we will review the epidemiology, clinical presentation, management, pathophysiology, and imaging indings of the most common spinal tumors.

INTRAMEDULLARY SPINAL CORD TUMORS Ependymoma Epidemiology. Spinal ependymomas account for 1.8% of all central nervous system (CNS) neoplasms in adults.10 Ependymoma is the most common primary spinal cord tumor in adults (60%) and second most common in children.14 Most ependymomas are low-grade tumors.3,41 Approximately 50% of CNS ependymomas occur in the spinal cord, and those arising in the conus medullaris/cauda equina are generally of the myxopapillary type. Ependymomas are usually sporadic but can be associated with neuroibromatosis type 2 (NF2). Approximately

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33% to 53% of patients with NF2 have spinal cord ependymomas, which can be multiple in up to 58% of patients.39,51,52

Presentation and Natural History. The peak incidence for presentation for ependymomas is in the fourth to ifth decade of life. There is a slight male predominance for the intramedullary type. The cervical spinal cord is the most common location, followed by the thoracic and the conus medullaris.3,27,67 Patients commonly present with neck/back pain (95%) and have variable degrees of myelopathy with bilateral motor and sensory deicits for an average of 2 to 3 years prior to the time of diagnosis. The signs and symptoms usually spare the head and face.40 A signiicant number of patients with spinal cord ependymomas are asymptomatic, and surveillance with serial imaging and physical examination is advised when looking for disease progression.21 It is recommended that a safe surgical intervention be performed promptly in patients with a decline in neurologic function.21,52 Ependymomas usually have a plane of dissection, and gross total resection is possible and curative, with 5- and 10-year survival rates of 58% to 100%.21,41 Low-grade ependymomas have a low risk of local recurrence or metastatic disease. Residual tumor or rupture of the capsule during surgery increases the chances of local recurrence and development of metastases. Follow-up for ependymomas includes an immediate postoperative MRI and clinical examination, repeated at 6 and 12 months, and then annually for 10 years.

Pathophysiology. Spinal cord ependymoma is a neoplasm that originates from the ependymal lining of the spinal cord central canal (see Fig. 30-2). The majority of ependymomas are of the cellular type, World Health Organization (WHO) grade II with low tendency to iniltrate the normal surrounding tissues. Generally there is a distinct plane between the tumor and adjacent normal cord, and a thin capsule may be present. The myxopapillary variant is a WHO grade I tumor and is found only at the conus medullaris (intramedullary) and ilum terminale/cauda equina (extramedullary-intradural) (Fig. 30-3).

Imaging. The most common imaging inding on CT and radiographs is scoliosis and nonaggressive bone remodeling. This is more often seen in ependymomas of the lower spinal canal and ilum.26 CT and CT myelograms should be reserved only for patients who have contraindications for MRI.61 MRI is the most appropriate imaging modality for evaluating any patient suspected of spinal cord pathology.61 The MRI examination should include a combination of sagittal T1- and T2weighted imaging, short tau inversion recovery (STIR), susceptibilityweighted imaging (SWI), diffusion-weighted imaging (DWI); axial T1, T2, and SWI; and postgadolinium sagittal and axial T1 with fat suppression. Additional advanced imaging such as diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and magnetic resonance perfusion (MRP) can help better characterize the lesions.

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FIG 30-1 Anatomic locations of intramedullary (green), extramedullaryintradural (blue), and extradural (red) spinal tumors. (Illustrated by David Bier, University of Texas MD Anderson Cancer Center, Houston, TX.)

B

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FIG 30-3 Myxopapillary ependymoma of conus medullary (2 different cases). Case 1 A and B, Sagittal T1W and T2W images reveal a wellcircumscribed, encapsulated mass. Case 2, C, Patient with two wellcircumscribed and homogeneously enhancing lesions along the ilum terminale/cauda equina consistent with distal drop metastatic myxopapillary ependymoma (arrow).

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FIG 30-2 Most common locations of the three most common intramedullary tumors: ependymoma is central (green), astrocytoma is eccentric (red), and hemangioblastoma is dorsal subpial (blue). (Illustrated by David Bier, University of Texas MD Anderson Cancer Center, Houston, TX.)

Most ependymomas are well circumscribed and originate from the centrally located ependymal cells and grow centrifugally, with symmetric expansion of the cord (see Fig. 30-2). They generally span an average of four vertebral segments, but accompanying cord edema extends beyond the tumor margins.17,67 Ependymomas are iso- to hypointense on T1-weighted images and hyperintense on T2 sequences. About 90% of ependymomas enhance after contrast administration and show well-deined margins with a homogeneous pattern (70%80%); rarely they will have little or no contrast enhancement.26,45 Most ependymomas do not restrict on DWI, and the apparent diffusion coeficient (ADC) is similar or higher compared to normal tissue.37,76 Ependymomas frequently present with hemorrhage (20%-60%) easily seen on T2* gradient echo and even more conspicuous on SWI images as signal loss from blood products within the tumor or in its rostral and caudal margins, which is known as the cap sign.26,47,73 About 60% to 90% of ependymomas have associated cysts,67 which are classiied as tumoral or nontumoral. Tumoral cysts are usually located within the substance of the tumor and relect necrosis-hemorrhage that shows inhomogeneous signal intensity and peripheral contrast enhancement on MRI. Nontumoral cysts are nonenhancing; their signal is cerebro-

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FIG 30-4 Ependymoma. A, Sagittal T2W image shows an isointense to the cord mass with intratumoral areas of high signal and a non tumoral rostral polar cyst (white arrow). B, Post-contrast sagittal T1W image reveals a heterogeneously enhancing very well-circumscribed mass. A non-enhancing isointense to the CSF, non-tumoral superior polar cyst (black arrow). Syrinx distal to the tumor (arrow heads on A and B).

spinal luid (CSF) equivalent and extends either rostrally or caudally beyond the tumor margins26,58 (Fig. 30-4). Nontumoral cysts are not removed during surgery but just aspirated, drained, or shunted, which allows for a smaller laminectomy needed to only resect the solid tumor portions.

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PART II CT and MR Imaging of the Whole Body Astrocytoma

Other techniques such as DTI and its derived fractional anisotropy (FA) can be used in the evaluation of ependymomas. DTI can help depict the location, orientation, and anisotropy of white matter tracts adjacent to the tumor. Ependymomas tend to displace rather than destroy or iniltrate white matter tracts.64,71,74 In ependymomas there is a nonspeciic tumoral and peritumoral reduction in FA values (FA = 0.48 ± 0.04), which is indicative of local extracellular edema and/or decrease in number of white matter ibers, with increased extracellular space12,35,37 (Fig. 30-5). On MRP the relative cerebral blood volume (rCBV) may be elevated in ependymomas.37 MRS shows elevated choline, which correlates with cell proliferation and thus tumor malignancy, and lipids, which are associated with hypoxia, apoptosis, and necrosis.29,76,77

A

G

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Epidemiology. Astrocytomas are the most common intramedullary tumors in the pediatric population and young adults (60%) and the second most common intramedullary tumor in adults (30%).14,30 There is roughly similar male-to-female predominance.8 Astrocytomas are more commonly located in the cervicothoracic or thoracic segments.41

Presentation and Natural History. In adults the average age of onset is 30 years, which is earlier compared to ependymomas. The average duration of symptoms at the time of diagnosis is about 9 months but can be as long as 3 years. A shorter duration of symptoms is associated with higher tumor grades and poorer survival rates.8 The clinical presentation often consists of back pain and weakness.

D

E

F

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FIG 30-5 Ependymomas (2) in NF2 patient. The sagittal T2W A and postcontrast T1 B, images show a well circumscribed heterogeneous mass with patchy enhancement and intratumoral cyst in the proximal cord (arrow head) and a distal smaller solid and homogeneously enhancing lesion (arrow). C, The sagittal DWI) without signiicant DWI hyperintensity. The ADC value D, in both lesions is higher or similar (proximal lesion, 1.050 × 10−3; distal lesion, 0.912 × 10−3) to the normal cord (0.907 × 10−3), conirming the unrestricted behavior of these lesions. E, The colored orientation DTI map shows continuity of the normal cord in blue displaced dorsally; and absence of color at the tumor sites (arrows). The DTI tractography F and G, conirms the noniniltrative nature of the mass, with ibers being displaced and not entering the lesion. The fractional anisotrophy value H is decreased in the tumor (P = 0.138) compared to the normal cord (P = 0.628). The SWI I, shows subtle hypointense foci from prior hemorrhage, which is visible only on this sequence (arrow).

CHAPTER 30 Torticollis and scoliosis are usually seen in younger children. Insidious myelopathy in children should prompt a spinal MRI study.8,79 Lowgrade astrocytomas have an 80% 5-year survival rate compared to 30% for high-grade astrocytomas.41,44 There is an association of spinal cord astrocytomas with neuroibromatosis type 1 (NF1). Pilocytic astrocytoma tends to have a more benign biological behavior when it occurs in patients with NF1. Benign well-circumscribed pilocytic astrocytoma has a plane of dissection, and gross total resection can be attempted. However, WHO grade II, III, and IV astrocytomas are iniltrative, and total resection without injuring the normal tissue is seldom accomplished; therefore conservative decompression, partial tumor removal, cyst decompression, and tissue diagnosis is commonly performed. Radiotherapy and chemotherapy are recommended for iniltrative residual or recurrent high-grade tumors.16,21

Pathophysiology. Astrocytoma arises from astrocytic glial cells of the cord, with an afinity for the white matter tracts located in the periphery of the cord (see Fig. 30-2). Most are low-grade astrocytomas (70%-90%), either pilocytic astrocytoma (15% WHO grade I) or more commonly ibrillary astrocytoma (75% WHO grade II).3,40 On histo-

A

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logic evaluation, ibrillary astrocytoma shows widespread parenchymal iniltration, whereas pilocytic astrocytoma displaces rather than iniltrates the cord. High-grade anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV) are rare, accounting for about 10% to 30% of spinal cord astrocytomas.40,41 High-grade astrocytomas characteristically show mitotic activity and nuclear atypia. High-grade astrocytomas have a poor survival with higher recurrence and metastatic dissemination through the neuroaxis.30

Imaging. MRI is the most appropriate imaging modality, and CT/CT myelograms should be reserved for patients with contraindications for MRI.61 Astrocytomas are iniltrating poorly deined neoplasms and tend to be eccentrically located with asymmetric and fusiform cord expansion (see Fig. 30-2). Astrocytomas span about four or fewer vertebral segments at the time of presentation. Holocord involvement is rare and usually seen in pilocytic astrocytoma, mainly in children and adolescents.15,60 Astrocytomas are hypo- to isointense on T1 and hyperintense on T2 and STIR. Spinal astrocytomas usually enhance inhomogeneously in a nodular or patchy manner, and the enhancing tumor does not deine the true tumor margins (Fig. 30-6).

B

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FIG 30-6 Astrocytoma. The sagittal and axial T2-weighted images (A and D) show an ill-deined hyperintense mass with cord expansion and mild surrounding edema. B, Sagittal T1-weighted images show a slightly hypointense mass. C and E, Sagittal and axial T1-weighted postcontrast images show nodular inhomogeneously enhancing mass.

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PART II CT and MR Imaging of the Whole Body

Approximately 18% to 30% of astrocytomas do not enhance.63 Most astrocytomas do not restrict on DWI, and their ADC values are not signiicantly decreased.76 They may have tumoral cysts with peripheral contrast enhancement, as well as nonenhancing nontumoral polar cysts and syrinxes.58 Hemorrhage is uncommon compared to ependymomas, and surrounding edema is variable 65 (Fig. 30-7). On DTI astrocytomas show diffuse iniltration of the cord or disrupted white matter tracts from tumor invasion13,71 (see Fig. 30-7). There is a reduction in FA values in astrocytomas, similar to the ones seen in ependymomas (0.48 ± 0.2).12,35,37 MRP shows low to moderate rCBV and increased vascular permeability on derived permeability maps, and one glioblastoma with increased rCBV has been reported.36,37 MRS obtained in the solid component of pilocytic astrocytoma demonstrates elevated choline/N-acetylaspartate (NAA) ratio, ranging from 1.80 to 3.40 compared with 0.53 to 0.75 for normal tissue.12,22,23,31 This inding implies hypercellularity.

Hemangioblastoma Epidemiology. Hemangioblastoma (HB) is the third most common tumor, accounting for 2% to 8% of all IMSCTs.38,78 It occurs sporadi-

cally in 70% of patients, but in 30% is associated with von HippelLindau (VHL) disease. VHL patients have 3p chromosomal mutations in the VHL gene.78 Multiple and usually small ( 8 mm. Either reassessment CT scans at 3, 9, and 24 months to assess for stability in size or further evaluation with contrast-enhanced CT, CT-PET, or biopsy or resection. B. High-Risk Populations (History of Smoking or Other Exposure or Risk Factor) i. Nodule ≤ 4 mm. Reassessment at 12 months, and if stable no further evaluation is required. The exception is the nonsolid or partially solid nodule, for which reassessment may need to be continued to exclude risk of an indolent adenocarcinoma. ii. Nodule > 4 mm but ≤ 6 mm. Reassessment CT at 6 to 12 months and if stable again at 18 to 24 months. iii. Nodule > 6 mm but ≤ 8 mm. Reassessment CT at 3 to 6 months and if stable again at 9 to 12 months and 24 months. iv. Nodule > 8 mm. Either reassessment CT at 3, 9, and 24 months to assess stability or perform contrast-enhanced CT, CT-PET, or biopsy or resection. From MacMahon H, et al: Guidelines for management of small pulmonary nodules detected on CT scans: A statement from the Fleischner Society. Radiology 237:395–400, 2005.

as a more accurate determination of growth of PSNs.58 By multiplying nodule volume and density, mass measurements allow detection of growth of PSNs earlier and are subject to less variability than volume or diameter measurements. At present the determination of when and how to observe and image small nodules in the assessment of tumor growth rate has not been resolved. However, the Fleischner Society has guidelines for evaluation of an incidentally discovered solid nodule in an adult patient that integrate lesion morphology, growth rate, patient age, and smoking history (Box 37-2). In addition, to complement the recommendations for incidentally detected solid nodules, the Society has recently published recommendations speciically aimed at the management of GGNs and PSNs181,204 (Box 37-3). Importantly for GGNs and PSNs, risk factors such as smoking history, familial history of lung cancer, or exposure to carcinogenic agents are not considered in the current guidelines owing to a lack of suficient data. In addition, other issues to be aware of are that a slight temporary decrease in size can be seen, with adenocarcinomas manifesting as GGNs or PSNs owing to ibrosis or atelectasis; enlargement and/or increasing attenuation with or without the new appearance of a solid component during follow-up should be managed with a high degree of suspicion.204 5. Blood supply. Blood supply to malignant pulmonary nodules is qualitatively and quantitatively different from the blood supply

CHAPTER 37 to benign nodules. Contrast-enhanced CT can be used to image this difference by determining nodule enhancement. Typically, malignant nodules enhance more than 20 HU, whereas benign nodules enhance less than 15 HU288 (Fig. 37-17). A computeraided design (CAD) system using quantitative features to

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describe the nodule’s size, shape, attenuation, and enhancement properties has been reported to assist in the differentiation of benign and malignant nodules.269 The study showed that CAD using volumetric and contrast-enhanced data to evaluate solitary pulmonary nodules with a mean diameter of 25 mm (range, 6-54 mm) was useful in assisting in the differentiation of benign and malignant solitary pulmonary opacities.269 6. Metabolism. Metabolism of glucose is typically increased in lung cancer cells. Positron emission tomography (PET) using a d-glucose analog, luorine-18 luorodeoxyglucose (FDG), can be used as an additional study to improve the characterization of focal pulmonary opacities. However, because the intrinsic spatial resolution of a PET scanner is on the order of 5 to 7 mm, false-negative studies can result when nodules smaller than 1 cm in diameter are evaluated.126,216 FDG uptake can be assessed visually on PET images by comparing the activity of the lesion with that of the background, or the FDG uptake can be quantiied by using several parameters including standardized uptake value (SUV) or local metabolic rate of glucose (Ki = inlux constant). SUV of greater than 2.5 is generally considered to be indicative of malignancy, but this number is typically not used as a rigid cutoff to differentiate between a benign and a malignant nodule. In a meta-analysis of 40 studies, FDG PET was found to operate at a point on the summary receiver operating characteristic curve corresponding to a sensitivity of 96.8% and speciicity of 78%.108 Although there was no difference in diagnostic accuracy according to size, few data exist for nodules smaller than 1 cm in diameter.108 It is important to emphasize that the published data regarding FDG PET evaluation of solitary pulmonary opacities indicating high sensitivity, speciicity, and accuracy mostly pertains to nodules that are both solid and 1 cm or greater in diameter. Because the probability of malignancy is high when a solid nodule of 1 cm or greater has increased FDG uptake (Fig. 37-18), these nodules should be biopsied or resected, although close radiologic

Recommendations for Management of Subsolid Pulmonary Nodules Detected at CT BOX 37-3

A. Recommendations for Management of Incidentally Detected Solitary Ground-Glass and Part-Solid Nodules i. Solitary pure ground-glass nodules (GGNs) ≤ 5 mm require no CT follow-up. ii. Nodule > 5 mm. Initial follow-up CT at 3 months to conirm persistence, then annual surveillance CT for a minimum of 3 years. iii. Solitary part-solid nodules (PSNs). Initial follow-up CT at 3 months to conirm persistence. If persistent and solid component < 5 mm, then yearly surveillance CT for a minimum of 3 years. If persistent and solid component > 5 mm, then biopsy or surgical resection. Consider PET-CT for PSNs > 10 mm. B. Recommendations for Management of Incidentally Detected Multiple Ground-Glass and Part-Solid Nodules i. Pure GGNs < 5 mm. Obtain follow-up CT at 2 and 4 years. ii. Pure GGNs > 5 mm without a dominant lesion(s). Initial follow-up CT at 3 months to conirm persistence, and then annual surveillance CT for a minimum of 3 years. iii. Dominant nodule(s) with part-solid or solid component. Initial follow-up CT at 3 months to conirm persistence. If persistent, biopsy or surgical resection is recommended, especially for lesions with > 5 mm solid component. From Naidich DP, et al: Recommendations for the management of subsolid pulmonary nodules detected at CT: A statement from the Fleischner Society. Radiology 266:304–317, 2013.

A

Neoplastic Disease of the Lung

B FIG 37-17 NSCLC appearing as an enhancing nodule after administration of contrast material. A, Non– contrast-enhanced CT scan shows a left lung nodule with an attenuation value of 24 HU. B, Contrastenhanced CT scan shows nodule enhancement of 70 HU and central necrosis. Enhancement of more than 20 HU suggests malignancy. Resection revealed non–small cell cancer. (Courtesy Tom Hartman, MD, Mayo Clinic, Rochester, Minn.)

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B

A

FIG 37-18 NSCLC manifesting as a hypermetabolic nodule on an integrated CT-PET scan with FDG. A, CT scan shows a spiculated nodule in the right upper lobe. The irregular margin suggests malignancy. Note diffuse emphysema. B, Axial fused CT-PET image with FDG shows increased uptake within the nodule when compared to adjacent mediastinum; indings are suspicious for malignancy. Transthoracic needle aspiration biopsy revealed adenocarcinoma.

surveillance is an option if the clinical likelihood of infection is high. Although FDG PET can reduce the number of benign nodules resected, benign neoplasms and nodules due to infection and inlammation (e.g., rheumatoid nodules, tuberculosis, histoplasmosis) can result in increased FDG uptake. When FDG uptake by a solid nodule 1 cm or greater in diameter is low, the likelihood of malignancy is generally considered to be low. However, in a recent study of 360 patients with lung nodules evaluated by FDG PET, 43 patients had solid nodules with an SUV less than 2.5, 16 of which were malignant.120 In this study visual analysis was as accurate as semiquantitative evaluation, and the probability of malignancy was very low if FDG uptake was visually absent and 60% if visually present. False-negative PET results also tend to occur with carcinoid tumors and mucinous adenocarcinomas.74,129 False-negative PET results can also occur in malignant nodules that are smaller than 1 cm in diameter or have ground-glass or part-solid morphology. Nomori et al. reported that 9 of 10 well-differentiated adenocarcinomas manifesting as ground-glass nodular opacities were falsely negative on FDG PET, while 4 of 5 benign ground-glass nodular opacities were falsely positive.216 The sensitivity (10%) and speciicity (20%) for ground-glass opacities in this study were signiicantly lower than those for solid nodules (90% and 71%, respectively).

Staging Because treatment and prognosis depend on the anatomic extent of NSCLC at initial presentation, accurate assessment is important. The seventh edition of the American Joint Committee on Cancer (AJCC) is used to describe the extent of NSCLC in terms of the primary tumor (T descriptor), lymph nodes (N descriptor), and metastases (M descriptor).233,238,239,260 The TNM descriptors can be determined clinically (history, physical examination, radiologic imaging) or by pathologic analysis of samples obtained by biopsy or surgery. In general the clinical stage underestimates the extent of disease when compared with the pathologic stage. In terms of the descriptors, radiologic imaging is usually directed at detecting nonresectable disease (N3 or M1). The detection of contralateral nodal (N3) and/or metastases (M1a, M1b) are important because these typically preclude surgical resection or require additional chemotherapy or radiotherapy. However, there is

currently little consensus on the imaging that should be performed for appropriate staging evaluation in patients presenting with NSCLC. The American Society of Clinical Oncology (ASCO) has published evidence-based guidelines for the diagnostic evaluation of patients with NSCLC.230 In the staging of locoregional disease these guidelines recommend that a chest radiograph and contrast-enhanced chest CT that includes the liver and adrenals should be performed. In addition, whole-body FDG PET is an integral component of NSCLC staging; it improves detection of nodal and distant metastases and frequently alters patient management.83,165,244,310,312 FDG PET complements radiologic indings, and the 2003 ASCO recommendations are that FDG PET should be performed when there is no evidence of distant metastatic disease on CT.230 Presently, FDG PET is usually used together with CT because the relatively poor spatial resolution of FDG PET limits its utility in the evaluation of the primary tumor (T descriptor) and in the determination of the precise anatomic location of regions of focal increased FDG uptake (N and M descriptors).

Primary Tumor (T) Status. The T status deines the size, location, and extent of the primary tumor (Box 37-4). There are numerous changes to the T descriptor in the seventh edition of the TNM classiication of lung cancer that are based on differences in survival: (1) T1 is now subclassiied as T1a (≤2 cm) or T1b (>2 cm to ≤ 3 cm); (2) T2 is now subclassiied as T2a (>3 cm to ≤ 5 cm or T2 by other factor and ≤ 5 cm) or T2b (>5 cm to ≤ 7 cm); (3) T2 tumors larger than 7 cm are reclassiied as T3; (4) T4 tumors by additional nodule(s) in the lung (primary lobe) are reclassiied as T3; (5) M1 by additional nodule(s) in the ipsilateral lung (different lobe) is reclassiied as T4; and (6) T4 pleural dissemination (malignant pleural effusions, pleural nodules) is reclassiied as M1.238 Because the extent of the primary tumor determines therapeutic management (surgical resection or palliative radiotherapy or chemotherapy), imaging is often performed to assess the degree of pleural, chest wall, and mediastinal invasion. Invasion of the chest wall by a primary NSCLC tumor of any size is designated T3, and en bloc resection (removal of lung parenchyma in continuity with a portion of the adjacent parietal pleura and chest wall) is considered the treatment of choice.63,160,184 In this regard, NSCLC invading the chest wall accounts for 5% to 8% of resected cases. The main objectives of preoperative imaging in patients presenting with a peripheral NSCLC abutting the

CHAPTER 37 BOX 37-4

Neoplastic Disease of the Lung

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International Association for the Study of Lung Cancer TNM Descriptors

T—Primary Tumor TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor ≤ 3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus) T1a Tumor ≤ 2 cm in greatest dimension1 T1b Tumor > 2 cm but not > 3 cm in greatest dimension T2 Tumor > 3 cm but not > 7 cm; or tumor with any of the following features2: • Involves main bronchus 2 cm or more distal to the carina • Invades visceral pleura • Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung T2a Tumor > 3 cm but not > 5 cm in greatest dimension T2b Tumor > 5 cm but not > 7 cm in greatest dimension T3 Tumor > 7 cm or one that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus < 2 cm distal to the carina1 but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe as the primary T4 Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina; separate tumor nodule(s) in a different ipsilateral lobe to that of the primary

N—Regional Lymph Nodes NX Regional lymph nodes cannot be assessed. N0 No regional lymph node metastasis N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s) N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) M—Distant Metastasis M0 No distant metastasis M1 Distant metastasis M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural or pericardial effusion3 M1b Distant metastasis Notes 1 The uncommon supericial spreading tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classiied as T1a. 2 T2 tumors with these features are classiied T2a if ≤ 5 cm or if size cannot be determined, and T2b if > 5 cm but not > 7 cm. 3 Most pleural (pericardial) effusions with lung cancer are due to tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) luid are negative for tumor, and the luid is nonbloody and is not an exudate. Where these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be classiied as M0.

Reprinted with permission courtesy of the International Association for the Study of Lung Cancer. Copyright © 2009 IASLC.

pleura are to determine whether chest wall resection is required and to evaluate for mediastinal nodal metastasis, because this generally precludes resection.184 Besides nodal metastasis, other factors that inluence survival are completeness of resection and the extent of chest wall invasion.160 CT is useful in conirming gross chest wall invasion (Fig. 37-19) but is inaccurate in differentiating between anatomic contiguity and subtle invasion. Findings suggestive of chest wall invasion include63,155,241: • Tumor-pleura contact extending over more than 3 cm • An obtuse angle at the tumor-pleura interface • Thickening of the pleura or increased attenuation of the extrapleural fat adjacent to the tumor Obliteration of the extrapleural adipose plane has been reported to have the best sensitivity (85%) and speciicity (87%) for chest wall invasion by a peripheral lung cancer, whereas the length of the tumorpleura contact has a sensitivity of 83% and speciicity of 80%.241 Although magnetic resonance imaging (MRI) offers superior soft tissue contrast resolution, the sensitivity (63%-90%) and speciicity (84%-86%) of MRI in identifying chest wall invasion is similar to that of CT155,222,237,317 (Fig. 37-20). Respiratory dynamic MRI has been proposed as a complementary imaging modality to CT in determining chest wall invasion (sensitivity 100%, speciicity 83%) but is overall not widely used in the evaluation of subtle chest wall invasion.7 However, MRI is particularly useful in the evaluation of superior sulcus (Pancoast) tumors and can be used to assess invasion of the brachial plexus, subclavian vessels, and vertebral bodies38 (Fig. 37-21).

Imaging with CT or MRI is useful in conirming gross invasion of the mediastinum (Figs. 37-22 and 37-23), but these modalities are inaccurate in determining subtle invasion (56%-89% and 50%-93%, respectively).155,317 CT and MRI indings that can be useful in suggesting subtle mediastinal invasion include127,155: • Tumor-mediastinal contact extending over more than 3 cm • Obliteration of the fat plane between the mediastinum and tumor • Tumor contacting more than 90 degrees of the aortic circumference The International Staging System for Lung Cancer combines the T descriptors with the N and M descriptors into subsets or stages that have similar treatment options and prognosis (see Table 37-1). However, it is important to realize that although a T4 descriptor generally precludes resection, patients with cardiac, tracheal, and vertebral body invasion are designated in the seventh edition staging system as being potentially resectable (stage IIIa) in the absence of N2 and/or N3 disease.92,135,160 The largest surgical experience for T4 involvement is in patients with carinal invasion, with less surgical resection experience with tumors invading the atrium, superior vena cava, aorta, and vertebral bodies.30,46,60,76,160,195,240,245 Surprisingly, complete surgical resection has been reported to be possible in many of these patients that on initial staging would have been denied surgery. Besides an improvement in locoregional control, patients who could be completely resected also showed improvement in long-term survival rates that were unforeseen considering their initial clinical staging.160

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M

* A

B FIG 37-19 NSCLC and chest wall invasion. A, Posteroanterior chest radiograph shows a large cavitary right lower lobe lung mass (arrows) and destruction of the posterior aspect of the right seventh rib (arrowheads). B, CT conirms the cavitary mass (M) and destruction of the adjacent rib (*). Note extension of the mass into the chest wall (arrowheads).

* *

B

A

FIG 37-20 SCLC and chest wall invasion. A, CT shows a large, well-circumscribed, peripheral lung mass with invasion of the chest wall. B, Coronal fast-spin echo MRI shows mass abutting the chest wall and the surrounding ribs (*) and extending through the intercostal space into the soft tissues of the chest wall (arrow).

Regional Lymph Node (N) Status. The presence and location of nodal metastasis are of major importance in determining management and prognosis in patients with NSCLC.259 To enable a consistent and standardized description of N status, nodal stations are deined by the relation to anatomic structures or boundaries that can be identiied before and during thoracotomy (Fig. 37-24). The N descriptors in the seventh edition of the TNM classiication of lung cancer have been

maintained because there were no signiicant survival differences in analysis by station.260 However, it proposed that lymph node stations could be grouped together in 6 zones within the current N1 and N2 patient subsets for further evaluation. Zones were deined as peripheral (stations 12, 13, 14) or hila (stations 10, 11) for N1 and upper mediastinal (stations 1, 2, 3, 4), lower mediastinal (stations 8, 9), aortopulmonary (stations 5, 6), and subcarinal (station 7) for N2 nodes (see

CHAPTER 37

Neoplastic Disease of the Lung

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A M

M

PA

R

*

LA

FIG 37-23 NSCLC invading the left atrium. Double inversion recovery FIG 37-21 Superior sulcus (Pancoast) tumor with chest wall invasion and involvement of the brachial plexus. Coronal T1-weighted MRI shows a mass (M) in the apex of the right hemithorax, with invasion into the neck. The mass surrounds the subclavian artery (*) and brachial plexus. R, irst rib.

FIG 37-22 NSCLC with mediastinal invasion. CT scan shows a large left upper lobe mass with invasion of the anterior mediastinum. Broad abutment and loss of soft tissue plane between the mass and the transverse aorta suggest vascular invasion.

Fig. 37-24).260 This proposal is based on survival analysis by anatomic location (or zone) of involved nodes, the number of zones involved, and presence of skip metastases. Size is the only criterion used to diagnose nodal metastases, with nodes greater than 10 mm in short-axis diameter considered abnormal. However, an inherent limitation is that lymph node size is not a reliable parameter for the evaluation of nodal metastatic disease in patients with NSCLC.234,293 Prenzel et al. recently reported that in 2891 resected hilar and mediastinal nodes obtained from 256 patients with NSCLC, 77% of the 139 patients with no nodal metastases had at least

contrast-enhanced single breath-hold coronal MRI shows an enhancing right upper lobe mass (M) that extends via the right superior pulmonary vein into the left atrium. A, aorta; LA, left atrium; PA, right main pulmonary artery.

one node greater than 1 cm in diameter.234 Furthermore, 12% of the 127 patients with nodal metastases had no nodes greater than 1 cm. A meta-analysis of 20 studies (3438 patients) evaluating CT accuracy for staging the mediastinum yielded a pooled sensitivity of 57% and speciicity of 82%.293 Thus, given the limitations of mediastinal nodal staging by CT, biopsy is recommended for conirmation of locoregional nodal metastases when the conirmation of nodal metastasis will have an impact on patient management. Because surgical resection and potential use of adjuvant therapy are dependent on the patient’s N descriptor, attempts have been made to improve the accuracy of detection of nodal metastases. FDG PET complements CT indings and provides information on locoregional nodal staging that affects management14,28,107,244 (Fig. 37-25). In a metaanalysis (17 studies, 833 patients) comparing PET and CT in nodal staging in patients with NSCLC, the sensitivity and speciicity of FDG PET for detecting mediastinal lymph node metastases ranged from 66% to 100% (overall 83%) and 81% to 100% (overall 92%), respectively, compared to sensitivity and speciicity of CT of 20% to 81% (overall 59%) and 44% to 100% (overall 78%), respectively.28 Because of the improvements of nodal staging when PET-CT is incorporated into the imaging algorithm of those patients with potentially resectable NSCLC, PET-CT should be performed in all patients without CT indings of distant metastasis, regardless of mediastinal nodal size, to direct nodal sampling as well as to detect distant occult metastasis. Although FDG PET for nodal staging is cost-effective and can reduce the likelihood that a patient with mediastinal nodal metastases (N3) that would preclude surgery will undergo attempted resection, the number of false-positive results due to infectious or inlammatory etiologies are too high to preclude mediastinoscopy. In an attempt to determine the necessity for invasive sampling after PET and CT imaging, a meta-analysis evaluated the association between the size of mediastinal nodes and the probability of malignancy.59 The authors reported a 5% posttest probability for N2 disease in patients with a negative FDG PET if the mediastinal nodes were 10 to 15 mm on CT and suggested these patients should proceed directly to thoracotomy.

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In patients with a negative FDG PET and lymph nodes 16 mm or larger on CT, the posttest probability for N2 disease was 21%, suggesting that these patients should have mediastinoscopy prior to thoracotomy. In patients with a positive FDG PET the posttest probability of malignancy was 62% if the nodes were 10 to 15 mm on CT and 90% if the nodes were 16 mm or larger. Although the authors did not suggest any management strategies regarding histologic conirmation of nodal metastasis when FDG PET is positive, N2/N3 should be histologically conirmed in patients potentially eligible for resection or adjuvant therapy.

Metastatic Disease (M) Status. The M descriptor in the seventh edition of the TNM classiication of lung cancer is subclassiied into M1a (additional nodules in the contralateral lung, malignant pleural effusion, pleural nodule[s], pericardial nodule[s]) and M1b (extrathoracic metastasis), and these metastases are common in patients with NSCLC at presentation.233,239 Up to 33% of patients with NSCLC have pleural metastases (M1a) at presentation. Pleural (or pericardial)

involvement (either multiple implants or a malignant effusion) is classiied as M1a because of slightly better survival than for distant metastatic sites and worse survival than for other categories of T4.233 The diagnosis of pleural metastases or malignant effusion, however, can be dificult to conirm. Pleural thickening and nodularity on CT scans suggests metastatic pleural disease (Fig. 37-26), but these abnormalities may not be present in association with a malignant effusion.249 Furthermore, cytologic evaluation has a mean sensitivity of 72% (range, 49%-91%) when at least two pleural luid specimens are analyzed.249 If the irst pleural luid analysis is nondiagnostic, a second specimen yields a diagnosis of malignancy in about 25% to 28% of patients.249 Although a nodule in the contralateral lung is potentially a metastasis (M1a), most (≈75%) of additional pulmonary nodules on CT imaging in patients with potentially operable clinical stage I to IIIa lung cancer are benign.65,106 An additional nodule may be a synchronous second primary lung cancer (incidence ≈ 1.5%-2% per patient per year).65 The AJCC rules are confusing with regard to stage classiication but indicate that when a patient has simultaneous bilateral cancers in paired

FIG 37-24 A, International Association for the Study of Lung Cancer Nodal Chart with stations and zones.

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Neoplastic Disease of the Lung

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FIG 37-24, cont’d B, Nodal deinitions. (Reprinted with approval by the International Association for Study of Lung Cancer and permission by Memorial Sloan Kettering, © 2009.)

organs, the tumors are classiied separately as independent tumors in different organs.11 To clarify the staging confusion, the American College of Chest Physicians (ACCP) recommends that when two lung cancers are deemed to be synchronous primary cancers, they be classiied with a TNM descriptor for each tumor.65 The role of imaging in detecting M1b metastases is not clearly deined. Because staging performed on the basis of clinical indings and conventional radiologic imaging incorrectly stage some patients with NSCLC, whole-body FDG PET is increasingly being used to improve the accuracy of staging. In fact the ACCP recommends PET imaging in patients with a normal clinical evaluation and no suspicious extrathoracic abnormalities on chest CT being considered for curative-intent treatment to evaluate for metastases (except the brain).161 In this regard, FDG PET has a higher sensitivity and

speciicity than CT in detecting metastases to the adrenals, bones, and extrathoracic lymph nodes. For instance, the results of the American College of Surgeons Oncology Trial reports a sensitivity, speciicity, positive predictive value, and negative predictive value of 83%, 90%, 36%, and 99%, respectively, for M1 disease.244 Whole-body PET imaging stages intra- and extrathoracic disease in a single study and detects occult extrathoracic metastases in up to 24% of patients selected for curative resection.182,231,244,310 The incidence of detection of occult metastases has been reported to increase as the staging T and N descriptors increase (i.e., 7.5% in early-stage disease to 24% in advanced disease).182 A randomized controlled trial of the role of PET in earlystage lung cancer (>90% of patients with T1-2/N0) showed that distant metastases were rarely detected (7 cm) T3 T3 T4 T4 M1a M1a M1b

IA IA IB IIA (IB) IIB (IA) IIB IIB (IIIB) IIIA (IIIB) IIIA (IV) IV (IIIB) IV IV

IIA IIA IIA (IIB) IIB IIIA (IIB) IIIA IIIA (IIIB) IIIA (IIIB) IIIA (IV) IV (IIIB) IV IV

IIIA IIIA IIIA IIIA IIIA IIIA IIIA (IIIB) IIIB IIIB (IV) IV (IIIB) IV IV

IIIB IIIB IIIB IIIB IIIB IIIB IIIB IIIB IIIB (IV) IV (IIIB) IV IV

T2 (>3 cm)

T3 invasion T4 (same lobe nodules) T4 (extension) M1 (ipsilateral lung) T4 (pleural effusion) M1 (contralateral lung) M1 (distant)

Shaded boxes highlight 7th edition changes in classiication, with 6th edition classiication in parentheses. Reprinted with permission courtesy of the International Association for the Study of Lung Cancer. Copyright © 2009 IASLC.

with SCLC seldom present at a stage for which surgery is appropriate. Nevertheless, small published series of resected SCLC have suggested that TNM pathologic staging correlates with survival of resected patients. The TNM system has demonstrated the ability to identify potential surgical candidates and may result in improved consistency in radiation treatment planning.143 Accordingly the IASLC has recommended that the TNM staging system replace the VALSG system for staging of SCLC.307

Although there is no consensus regarding the imaging and invasive procedures that should be performed in the staging evaluation of patients with SCLC, MRI has been advocated to assess the liver, adrenals, brain, and axial skeleton in a single study.140 Whole-body PET imaging improves the accuracy of staging of patients with SCLC.17,84,162,213 In this regard, Niho et al. performed FDG PET imaging in 63 patients diagnosed by conventional staging procedures as having limited-stage SCLC.213 Therapeutic management was changed in 5 patients (8%)

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A

C

B

FIG 37-31 SCLC with disseminated metastases at presentation. A, Posteroanterior chest radiograph shows a lobular 3-cm right upper lobe nodule (arrow) and hilar adenopathy (arrowhead). B, CT shows left adrenal metastasis (arrow). C, Axial contrast-enhanced cranial MRI shows an enhancing cerebral metastasis (arrow).

owing to detection of unsuspected distant metastases and change in stage from LD to ED. Evaluation of extrathoracic metastatic disease usually includes the following: 1. Bone marrow aspiration, 99mTc-MDP bone scintigraphy, and MRI. Patients with bone (30%) and bone marrow (17%-34%) metastases are often asymptomatic, and blood alkaline phosphatase levels are frequently normal.55,278,279 Because isolated bone and bone marrow metastases are uncommon, however, routine bone marrow aspiration and radiologic imaging for occult metastases are usually performed only if there are other indings of ED. 2. Brain MRI. CNS metastases are common (10%-27%) at presentation, and approximately 5% of patients are asymptomatic.3,55 Because therapeutic CNS radiation and chemotherapy can decrease morbidity and improve prognosis, routine MRI of the brain is recommended in patients with SCLC.55,72,308 3. CT or MRI of the abdomen. Metastases to the liver (30%) and retroperitoneal nodes (11%) are common at presentation.3,55 Because patients are often asymptomatic and liver function tests can be normal, staging evaluation routinely includes CT or MRI of the abdomen.

Other Lung Malignancies Sarcomatoid Carcinoma. Sarcomatoid carcinomas of the lung are poorly differentiated carcinomas containing carcinomatous and sarcomatous components.208,295,321 Molecular evidence supports the concept that these are carcinomas of the lung with a clonal origin from pluripotent stem cells capable of divergent differentiation into carcinomatous and sarcomatous components.295 They represent a clinicopathologic continuum, and ive subtypes are recognized: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma.295,321 Carcinomas with spindle or giant cells. Sarcomatoid carcinomas of the lung (pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma) are rare, comprising 0.3% to 1% of malignant lung neoplasms.208,295 They are a heterogeneous group of NSCLCs containing a sarcomalike component that histogenetically may represent a malignant epithelial neoplasm undergoing divergent tissue differentiation originating from a single clone.29,256 Most patients are men, and mean age at presentation is 65 years (range, 44-78 years).29,208 Most patients present with cough, dyspnea, hemoptysis, chest pain, or weight loss.208,256 Although sarcomatoid carcinomas are usually localized at presentation, distant metastases occur frequently and the prognosis is poor.208,321

CHAPTER 37 Radiologically these neoplasms can manifest either as large peripheral masses or as polypoid endobronchial lesions with atelectasis or postobstructive pneumonia.151,208,295,321 Calciication and cavitation are uncommon, but necrosis and hemorrhage can manifest as heterogeneous attenuation on CT.151,208,321 Hilar or mediastinal adenopathy is uncommon.208 Pleural effusion can occur as a result of local invasion.151 Metastases involve sites similar to those of lung cancer (lung, liver, bones, adrenals, brain).321 Pulmonary blastoma. Pulmonary blastoma is a rare malignancy that makes up an estimated 0.25% to 0.5% of primary lung tumors.87,166,173,309 The tumor derives its name from its histologic resemblance to fetal lung tissue. Pulmonary blastomas, however, are thought to arise from primitive pluripotential stem cells and may represent a variant of carcinosarcoma.321 Pulmonary blastomas are subdivided in three categories: well-differentiated fetal adenocarcinoma, classic biphasic pulmonary blastoma and pleuropulmonary blastoma, which is currently regarded as a separate entity. Welldifferentiated fetal adenocarcinoma is categorized as a variant of adenocarcinoma of the lung.296 Although the age range at presentation is wide (0-80 years), these tumors typically occur in adults, with a peak incidence between 40 and 60 years of age.87,166,173 However, pleuropulmonary blastomas usually occurs exclusively in children less than 15 years of age, with a median age of 3 years and one-fourth are hereditary.309 Patients are often symptomatic at presentation; cough, hemoptysis, and chest pain are frequent manifestations.4,159 Pediatric age patients typically present with fever and respiratory distress.36,309 The behavior of pulmonary blastomas is aggressive and the outcome is poor due to frequent relapses and metastases.36,51,87 Radiologically, pulmonary blastomas typically manifest as large (range, 2.5-26 cm), well-marginated masses located peripherally in the lung36,177,309 (Fig. 37-32). Multiple masses, cavitation, and calciication are rare. Local invasion of the mediastinum and pleura occurs in 8%

Neoplastic Disease of the Lung

and 25% of cases, respectively.87 Metastases to hilar and mediastinal lymph nodes are present in 30% of resected cases.87 Extrathoracic metastases are common and have a distribution similar to that of lung cancer.87,173

Pulmonary Neuroendocrine Neoplasms. Four major types of neuroendocrine neoplasms are recognized by the 2004 WHO Classiication of Tumors and are grouped into three histologic grades. Typical carcinoid is characterized as low-grade malignant neoplasm, atypical carcinoid as intermediate grade, and large cell neuroendocrine lung carcinoma and SCLC as high-grade malignancies. Carcinoid tumors. Primary pulmonary carcinoid tumors are lowgrade malignancies that constitute 1% to 2% of primary lung tumors.246,294 They are classiied histologically as typical (80%-90%) or atypical (10%-20%) tumors depending on the degree of cellular atypia.23,246,294 Typical carcinoid is a well-differentiated neoplasm with neuroendocrine histologic features of 5 mm or greater size with less than 2 mitoses per 10 HPF and no necrosis, whereas atypical carcinoid has 2 to 10 mitoses per 10 HPF or necrosis. The most useful immunohistochemical markers for identifying neuroendocrine neoplasms are chromogranin, CD56, and synaptophysin; Ki-67 is useful in differentiating typical carcinoid and atypical carcinoid from large cell neuroendocrine lung carcinoma and SCLC.246,294 Typical carcinoid tumors occur with equal frequency in men and women; the mean age at diagnosis is 35 to 50 years.275 Tumors usually arise in lobar, segmental, or proximal subsegmental bronchi and are generally 1 to 4 cm in size.95 However, increased detection of peripheral carcinoid tumors more recently has been attributed to widespread use of CT.189 Typical carcinoid tumors rarely metastasize to regional nodes or beyond the thorax. Atypical carcinoid tumors are usually discovered at a slightly older age (mean, 53-60 years), are often larger, and tend to occur more frequently in the peripheral aspect of the lungs.24,95,275

*

A

1007

B FIG 37-32 Pulmonary blastoma manifesting as a large pulmonary mass. A, Posteroanterior chest radiograph shows complete homogeneous opaciication of the left hemithorax and displacement of the mediastinum to the right. B, CT reveals a large lung mass and shows heterogeneous attenuation consistent with necrosis. There is subcarinal adenopathy due to metastatic disease (*). Note the complete compressive atelectasis of the left lung.

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PART II CT and MR Imaging of the Whole Body

They behave more aggressively than typical carcinoid tumors and frequently metastasize to regional nodes, lung, liver, and bone.95,242 In a published series of 661 resected carcinoid tumors (569 typical carcinoid, 92 atypical carcinoid) the 5-year survival was 97% and 78%, respectively. The 5-year survival of patients with atypical carcinoid tumors decreased to 60% if there was nodal involvement. In fact the reported difference in 5-year survival between typical carcinoid tumors and atypical carcinoid tumors may be much more related to the N status than to the histologic subtype, with N2 being the most important prognostic factor.40 Clinical manifestations depend on the histologic type and location of the carcinoid tumor. Peripheral tumors are usually asymptomatic, whereas central neoplasms can manifest as cough, hemoptysis, or recurrent infection (Fig. 37-33). Paraneoplastic manifestations such as

A

carcinoid syndrome (cutaneous lushing, bronchospasm, chronic diarrhea, and valvular heart disease) and Cushing’s syndrome are rare and more common with atypical carcinoid tumors.95,115,294 Some 40% to 50% of patients with carcinoid syndrome develop carcinoid heart disease, characterized by right-sided heart failure caused by ibrotic endocardial plaques.85,232 Carcinoid tumors most commonly manifest radiographically or on CT as central endobronchial masses with or without atelectasis or consolidation25,95 (Fig. 37-34). A peripheral well-marginated pulmonary nodule is a less common manifestation (Fig. 37-35). The tumors are usually less than 3 cm in size, although occasionally they may be as large as 10 cm in diameter.95,306 Calciication is detected by CT in approximately 25% of carcinoid tumors340 (Fig. 37-36). Hilar and mediastinal adenopathy and extrathoracic metastases are uncommon

B FIG 37-33 Typical carcinoid tumor manifesting as recurrent pulmonary infections. A and B, CT shows a mass in the segmental bronchus of the left lower lobe (arrows in A), left lower lobe volume loss, and distal bronchiectasis in the atelectatic lung (arrowheads in B).

M

A

B FIG 37-34 Typical carcinoid appearing as a central endobronchial lesion. A, Posteroanterior chest radiograph shows complete atelectasis of right lower lobe (arrowheads) with compensatory hyperinlation of the left lung. Note displacement of the anterior junction line (arrows). B, CT conirms atelectasis of the right lower lobe and reveals an endobronchial mass (M) with marked narrowing of the bronchus intermedius (arrow).

CHAPTER 37

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1009

T

FIG 37-35 Typical carcinoid manifesting as a solitary peripheral nodule. CT shows a well-circumscribed small nodule in the left lower lobe (arrow).

FIG 37-37 Adenoid cystic carcinoma manifesting as a tracheal mass. CT shows a circumferential soft tissue trachea mass (T) and narrowing of the trachea.

FIG 37-36 Atypical carcinoid tumor with rib and hepatic metastases at presentation. CT shows a large endobronchial mass with dense punctate calciication.

at presentation in patients with typical carcinoid tumors and occur more frequently in patients with atypical carcinoid tumors.24,95 Beasley et al. reported that regional and distal nodal metastases are present in 40% to 50% of patients at presentation, and 10% will have distant metastases.24 Although routine use of scintigraphy with somatostatin analogues (indium 111, octreotide, or lanreotide) can be useful for localization of occult tumors, this imaging is usually reserved for staging or to assess response to therapy.115,232 On FDG PET imaging, pulmonary carcinoid tumors usually have lower FDG uptake than expected for malignant tumors.47,74

Salivary Gland–Type Carcinomas Mucoepidermoid carcinoma. Mucoepidermoid carcinoma (formerly categorized as bronchial adenoma) is a rare tracheobronchial tumor of low malignant potential. It is of bronchial gland origin and composed of distinct areas of squamoid cells, mucus-secreting cells, and cells of intermediate type.335 Although patients vary widely in age at presentation, the tumors are more common in adults, with a peak incidence between 35 and 45 years.270,336 They typically occur in the main or lobar bronchi but in rare instances may be located in the trachea and periphery of the lung.336 They are usually slow-growing, low-grade neoplasms with a benign clinical course.326 Although

occasionally they exhibit aggressive local behavior, metastases are uncommon.122,326,336 Radiologically the tumor usually manifests as a central endobronchial mass and less commonly as a polypoid intraluminal tracheal or peripheral lung nodule or a mass. Adenoid cystic carcinoma (cylindroma). Adenoid cystic carcinoma (formerly categorized as a bronchial adenoma) is an uncommon primary tumor of the lung. It occurs most often in the trachea (Fig. 37-37) and main bronchi, although 10% to 15% are located peripherally in the lung.10,27,53 Adenoid cystic carcinomas occur with equal frequency in men and women; the mean age at diagnosis is 45 to 51 years.186,198 Although review of the literature provides limited information regarding their biological behavior in lung, they typically exhibit slow progressive growth. Metastases to regional lymph nodes, lung, bone, liver, and brain are common but tend to occur late in the disease.9,27 Radiologically the tumor usually manifests as an endotracheal or endobronchial mass that is typically lobulated or polypoid and encroaches on the airway lumen. Masses can be circumferential and may manifest as diffuse stenosis.188 A less common manifestation is a peripheral lung nodule or mass.93

Mesenchymal Tumors Primary pulmonary sarcomas. Primary lung sarcomas with a vascular origin (angiosarcomas, epithelioid hemangioendotheliomas) are rare primary tumors of lung.18,285,319 Most angiosarcomas are lung metastases, and the existence of primary pulmonary angiosarcoma has been questioned.277 The tumor usually occurs in young adults, and the most frequent radiologic inding is multiple bilateral nodules.285 Epithelioid hemangioendothelioma is typically seen in women younger than age 40 (range, 7-76 years).18,42,252,255,319 Most patients are asymptomatic at presentation; complaints include weight loss, dyspnea, chest pain, and cough. Epithelioid hemangioendotheliomas are usually indolent, with survival reported up to 24 years following resection.52 However, loss of weight, anemia, pulmonary symptoms, and hemorrhagic pleural effusions are signiicant factors of poor prognosis, with a median survival of less than 1 year.18 Pulmonary

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PART II CT and MR Imaging of the Whole Body

A

B

C FIG 37-38 Epithelioid hemangioendothelioma appearing as multiple pulmonary nodules. A, Posteroanterior chest radiograph shows numerous small bilateral pulmonary nodules. Note the absence of hilar and mediastinal adenopathy. B, CT conirms the numerous small, bilateral, well-circumscribed nodules. C, CT scan of the abdomen reveals small, bilateral, low-attenuation hepatic epithelioid hemangioendotheliomas.

epithelioid hemangioendothelioma usually manifests radiologically as multiple 1- to 2-cm bilateral pulmonary nodules, although single nodules and unilateral distribution have been reported in approximately 25% of patients18,52,255 (Fig. 37-38). Irregular thickening of the bronchovascular bundles and perilobular structures due to lymphangitic spread, and associated multiple pulmonary nodules as well as multiple small peripheral nodules bilaterally have been described on HRCT as rare manifestations of pulmonary epithelioid hemangioendothelioma.262 Calciication is rarely detected but is common histologically.52,255 Hilar adenopathy and pleural effusions occur in 9% of patients.255 Multiorgan involvement, most commonly the liver, occurs occasionally and may represent metastatic disease or multicentric origin of the tumor.37,43,71,73,257 Primary lung sarcomas with a spindle origin are rare, accounting for fewer than 0.5% of primary lung malignancies.15,285 Spindle cell sarcomas (malignant ibrous histiocytoma, hemangiopericytoma, ibrosarcoma, leiomyosarcoma, synovial sarcoma) are the most common primary pulmonary sarcomas.145,197,285,338 They are a heterogeneous group of tumors with morphologic similarities to their extrathoracic counterparts.15 The diagnosis is established only after metastatic disease and sarcomalike primary lung malignancies (sarcomatoid carcinomas) have been excluded.15,87,138,208 Pulmonary sarcomas have a peak incidence in the ifth and sixth decades.87,139,197,285,337 The tumors are usually slowly growing with late metastases, and the prognosis is generally better than that with lung cancer.285

Radiologically, pulmonary sarcomas are more commonly located peripherally, although central and endobronchial masses are reported.15,139,197,285,337 Lesions range in size from 0.6 to 25 cm; they are typically sharply marginated and occasionally calciied15,117,145,197,285 (Figs. 37-39 and 37-40). Cavitation is uncommon, although CT can show heterogeneous attenuation resulting from necrosis within the mass.117,145 Diagnostic angiographic features have been reported for hemangiopericytomas in the soft tissues and bone.117,327 The pathognomonic hypervascularity that occurs as a result of the numerous vascular spaces within the tumor, however, are seldom seen on CT scans or MRIs of primary pulmonary hemangiopericytomas (Fig. 37-41).

LYMPHOPROLIFERATIVE DISORDERS Primary Lymphomas Primary pulmonary lymphomas account for fewer than 1% of all lymphomas.79,292 The diagnosis is generally considered if the lymphoid proliferation is monoclonal and there are no sites of extrathoracic lymphoma at presentation or for at least 3 months after diagnosis.210,292 However, criteria used to deine primary pulmonary lymphomas are variable; some authors restrict the diagnosis to pulmonary parenchymal disease only, but others include hilar adenopathy with or without mediastinal adenopathy. Primary pulmonary lymphomas encompass a histologic spectrum of malignant lymphomas including non-Hodgkin’s lymphoma,

CHAPTER 37

Neoplastic Disease of the Lung

1011

A

M M

P P

L L

B

C FIG 37-39 Synovial carcinoma of left lung manifesting as a large mass. A, CT shows a large mass in the left lower lobe with a small focal calciication (arrow). A small pleural effusion can be seen. B and C, Coronal T1-weighted (B) and fast-spin echo (C) MRIs show a large heterogeneous mass abutting the diaphragm without signs of invasion. There is a small pleural effusion (P). L, liver; M; mass.

Hodgkin’s lymphoma, and lymphoproliferative disorders associated with immunodeiciency states (e.g., posttransplant lymphoproliferative disorders, acquired immunodeiciency syndrome).48,116 Primary pulmonary lymphomas are typically non-Hodgkin’s lymphomas of B-cell immunophenotype composed of monoclonal lymphocytic cells with low histologic grade, and they are classiied as extranodal marginal zone lymphomas.81,158,175,210 Most primary extranodal lymphomas arise from mucosa-associated lymphoid tissue, and the Revised European-American Lymphoma classiication recommends that those lymphomas with low-grade features be referred to as marginal zone

B-cell lymphoma of the mucosa-associated lymphoid tissue type, whereas those with high-grade features be referred to as diffuse large B-cell nonHodgkin’s lymphoma.210,211,316 Primary pulmonary lymphomas tend to remain localized to the lung, although recurrence after treatment (often at extrapulmonary sites) occurs in up to 50%.49,81,158,175 In the lung the neoplastic cells typically iniltrate the bronchiolar mucosal epithelium, forming lymphoepithelial lesions.210 High-grade non-Hodgkin’s lymphomas, which constitute approximately 13% of primary pulmonary lymphomas, are usually B-cell tumors with aggressive behavior and a poor 5-year

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PART II CT and MR Imaging of the Whole Body

A

B FIG 37-40 Malignant ibrous histiocytoma manifesting as a large lung mass. A, Posteroanterior chest radiograph shows a left upper lobe mass. B, CT shows a large lobular mass and reveals narrowing of the left main pulmonary artery (arrowheads).

A

B

C FIG 37-41 Hemangiopericytoma appearing as a large hypervascular mass. A, Contrast-enhanced CT shows a large right lower lobe mass. Large vessels can be seen within the mass. B and C, Axial T1-weighted (B) and fast-spin echo (C) MRIs show a heterogeneous mass in the right hemithorax. Flow voids can be seen within the intratumoral vessels.

CHAPTER 37

A

Neoplastic Disease of the Lung

1013

B FIG 37-42 Primary pulmonary lymphoma manifesting as bilateral pulmonary opacities. A and B, CT shows focal poorly marginated nodular opacities in both lungs. Air bronchograms within opacities are suggestive of the diagnosis.

survival rate.49,81,158,175 Most patients are 55 to 60 years old, although the age range is wide.175 Patients with low-grade lymphomas are usually asymptomatic at presentation, whereas patients with high-grade tumors usually present with cough, fever, or weight loss.49 Radiologic manifestations include a solitary nodule or mass, multiple nodules or masses, focal or multifocal consolidation, reticulonodular opacities, and atelectasis49,81,153,171,217 (Fig. 37-42). Hilar adenopathy is rare, and pleural effusions occur in 7% to 25% of patients.49,158

BENIGN NEOPLASMS OF THE LUNG HAMARTOMA Hamartomas constitute 0.25% of all primary lung tumors; although uncommon they are the most common benign tumor of the lung.265 The term hamartoma was initially used to describe lesions with an abnormal composition or disorganized arrangement of normal lung tissue. However, hamartomas are now considered true neoplasms containing a mixture of epithelial and mesenchymal tissues.273 Pulmonary hamartomas typically occur in patients older than 30 years, with a peak incidence in the sixth decade (range, 0-76 years).118,218,235,265 Most patients are asymptomatic; symptoms are typically present with central endobronchial lesions and include hemoptysis, recurrent pneumonia, and dyspnea.88,99,265 Hamartomas are typically solitary, well-marginated, slightly lobular nodules or masses that are less than 4 cm in size (range, 1-30 cm)88,99,235,265 (Fig. 37-43). Most are located peripherally within the lung. Endobronchial hamartomas are less common (up to 20% of cases).88,118 Calciication has been reported in up to 50% but is probably present in fewer than 5% of hamartomas.168,273 Fat (CT attenuation, −40 to −120 HU) occurs in up to 50% of cases and is a diagnostic feature.273 Rare radiographic manifestations include cavitation and multiple pulmonary hamartomas.152

GRANULAR CELL TUMOR Granular cell tumors (formerly granular cell myeloblastomas) are uncommon benign mesenchymal neoplasms that are thought to arise from Schwann cells and usually present as a small solitary skin or submucosal nodule.61,187 Pulmonary granular cell tumors are rare and constitute 6% to 10% of all granular cell tumors.1 Patients are usually adults (peak incidence, age 30-50 years; range, 0-59 years), and there is a higher incidence in African Americans.61,157,226,227,250 Most pulmo-

FIG 37-43 Hamartoma manifesting as a large mass. CT shows a right lower mass that has focal calciied regions as well as focal regions of low attenuation (attenuation, −60 HU) consistent with fat. The diagnosis is suggested by small areas of fat within the mass.

nary granular cell tumors manifest as small, central endobronchial masses (range, 0.3-6.5 cm).1,61,128 Multiple lesions, typically in the larger bronchi, are found in up to 25% of cases.61,128 Common radiologic indings include atelectasis and obstructive pneumonia, although slow-growing solitary pulmonary nodules or masses occur in 12% of cases.61,128,196

SCLEROSING HEMANGIOMA Primary pulmonary sclerosing hemangioma (formerly pneumocytoma, papillary pneumocytoma) is a benign tumor consisting of thin-walled vessels and connective tissue.67,214 Originally thought to represent a vascular tumor, it is now considered to arise from primitive respiratory epithelium.67,121 Most patients are asymptomatic women between 30 and 50 years of age (range, 15-77 years).146,284 However, cough and hemoptysis can occur.67 Radiologically, pulmonary hemangiomas usually manifest as peripheral, well-marginated, solitary pulmonary

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PART II CT and MR Imaging of the Whole Body

FIG 37-44 Clear cell tumor manifesting as a solitary pulmonary nodule. CT shows a well-circumscribed left upper lobe nodule with heterogeneous enhancement.

nodules or masses 0.4 to 8 cm in diameter (average, 3 cm).113,209 Multiple pulmonary nodules and calciication are rare.146,172 Marked contrast enhancement is typical on CT, and tumors typically are heterogeneous in attenuation.209 On pathologic examination this is due to the angiomatous, solid and sclerotic, and cystic composition of the tumor. The MRI appearance of the tumor is variable and has been reported to be both homogeneous and heterogeneous in signal intensity.89,113 However, MRI can be useful in suggesting the diagnosis when regions of different signal intensity are present in the tumor.89 On T1-weighted images, areas of high signal intensity correspond to regions of abundant clear cells, whereas on T2-weighted images, areas of low signal intensity correspond to ibrotic or hemorrhagic regions within the tumor. The areas of high signal intensity on T2-weighted images correspond to the hemangiomatous portions of the tumor. There is also variable contrast enhancement, with the areas demonstrating contrast enhancement corresponding to the hemangiomatous portions of the tumor.89,209

CLEAR CELL TUMOR Clear cell tumor is a rare neoplasm of the lung.91 Most patients are asymptomatic and between 50 and 60 years of age (range, 8-70 years).91,105 Almost all these tumors behave in a benign nature, although extrathoracic metastases have been reported.264 Clear cell tumors typically manifest radiologically as well-marginated solitary pulmonary nodules usually less than 3 cm in diameter (range, 0.7-12 cm)13,90,91,147,264,339 (Fig. 37-44).

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38 Mediastinal Disease Jared D. Christensen, Danielle M. Seaman, and H. Page McAdams

There are many excellent textbooks and articles on the mediastinum.86,93,105,126,128,237,353 This chapter references these articles and a review of the recent literature as the basis for a discussion of the anatomy, pathology, and radiologic manifestations of mediastinal diseases.

NORMAL ANATOMY Comprehensive knowledge of cross-sectional anatomy is required to accurately evaluate mediastinal abnormalities. Interpretation of mediastinal anatomy can be assisted by analyzing computed tomography (CT) images at speciic levels within the chest that are easily identiiable because of their characteristic anatomic landmarks and appearance.

Axial Plane Thoracic Inlet Level At the junction of the neck and the thorax, most of the mediastinal structures are vascular. The two brachiocephalic veins are formed as the internal jugular veins join the subclavian veins and are located posterior to the clavicular heads (Fig. 38-1). These veins are the most anterior and lateral of the six major vessels at this level. More medial are the two common carotid arteries, and just posterior to these are the subclavian arteries. The subclavian arteries and veins exit the mediastinum to enter the axilla after crossing over the irst rib. The esophagus is posterior or posterolateral to the trachea.

Left Brachiocephalic Vein Level The left brachiocephalic vein crosses the midline anterior to the arterial branches of the aorta and joins the more vertically orientated right brachiocephalic vein to form the superior vena cava (SVC) (Fig. 38-2). The internal mammary veins can often be identiied coursing posteriorly from a parasternal location to join the brachiocephalic veins. The innominate, left common carotid, and left subclavian arteries are located posterior to the left brachiocephalic vein and anterior to the trachea. The innominate artery is the more centrally located artery; the left common carotid artery (smallest of the three arteries) and the left subclavian artery are located to the left of the midline in a more lateral and posterior position. The esophagus maintains its position posterior or posterolateral to the trachea and anterior to the spine.

Aortic Arch Level The transverse arch crosses the mediastinum anterior to the trachea, coursing obliquely from right to left and from anterior to posterior (Fig. 38-3). The SVC is located adjacent to the anterior aspect of the transverse aorta to the right of the trachea. The fat-illed region

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posterior to the SVC, anterior to the trachea, and lateral to the aorta is the pretracheal or anterior paratracheal space. Anterior to the transverse aorta is the fat-illed prevascular space, a compartment of the anterior mediastinum that extends cephalad anterior to the great vessels of the aorta and the brachiocephalic veins. If present, the thymus gland is located in this space. Both of these spaces often contain a few small lymph nodes. The esophagus maintains its position posterior or posterolateral to the trachea and anterior to the spine.

Azygous Arch–Aortopulmonary Window Level The azygos vein, located anterior and slightly to the right of the spine, arches anteriorly and joins the SVC at this level (Figs. 38-4 and 38-5). The azygos arch may not be seen in its entirety on one slice and may be confused with lymphadenopathy. The ascending and descending aortas are visible as separate structures at this level. The ascending aorta is anterior to the trachea, and the descending aorta is posterolateral to the trachea on the left. Typically the ascending aorta (mean diameter 3.5 cm) is larger than the descending aorta (mean diameter 2.5 cm). The aortopulmonary window is a space located between the inferior aspect of the aortic arch and the superior aspect of the left main pulmonary artery. In some patients the close anatomic contiguity of these two structures prevents visualization of this space. The space is otherwise fat-illed and contains a few small lymph nodes, the left recurrent laryngeal nerve, and the ligamentum arteriosum. The esophagus maintains its position posterior to the trachea, anterior to the spine, and medial to the descending aorta.

Left Pulmonary Artery Level50,340 The main pulmonary artery is anterior and to the left of the ascending aorta (Figs. 38-6 and 38-7). The left pulmonary artery curves posteriorly from its origin from the main pulmonary artery and is located anterolateral to the left main bronchus at the level of the carina. The left superior pulmonary veins are located lateral to the posterior portion of the left pulmonary artery. On the right at the level of the carina is the origin of the right upper lobe bronchus. Anterior to the right upper lobe bronchus lies the right upper lobe pulmonary artery, or the truncus anterior. The right superior pulmonary veins are located anterior and lateral to the truncus anterior. The azygos vein is located posterior and to the right of the esophagus, while the hemiazygos vein parallels the course of the azygos but is to the left of the spine. The superior pericardial recess, a crescent-shaped extension of the pericardial space, is contiguous to the posterior aspect of the ascending aorta. The space often contains a small amount of luid and may occasionally be confused with a lymph node; however, its characteristic location, shape, and low attenuation allow conident identiication.

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RCC LCC A T S LV

RV

T AZ

RSC E

D

LSC E

FIG 38-1 Axial plane—thoracic inlet level. The trachea (T) and esophagus (E) are midline and separate the right and left vascular structures. LCC, left common carotid artery; LSC, left subclavian artery; LV, left brachiocephalic vein; RCC, right common carotid artery; RSC, right subclavian artery; RV, right brachiocephalic vein.

FIG 38-4 Axial plane—arch of the azygos vein or aortopulmonary window level. The azygos vein (AZ) arches from a posterior position along the midesophagus to join the superior vena cava (S), crossing over the right upper lobe bronchus. Between the ascending (A) and descending (D) aorta is the aortopulmonary window region. E, esophagus; T, trachea.

LV

BC LCC T A RV LSC

S

E

D

AZ E

FIG 38-2 Axial plane—left brachiocephalic vein level. The right (RV) and left (LV) brachiocephalic veins are anterior to the right brachiocephalic artery (BC), left common carotid artery (LCC), left subclavian artery (LSC), trachea (T), and esophagus (E).

FIG 38-5 Axial plane—aortopulmonary window level. The aortopulmonary window is between the ascending (A) and descending (D) aorta and the superior vena cava (S). AZ, azygos vein; E, esophagus.

ARCH

S T

Occasionally the superior pericardial recess extends more cephalad to the level of the brachiocephalic vessels and may be mistaken for a mass or mediastinal cyst. The use of thin sections can be helpful to distinguish this so-called high-riding pericardial recess from pathologic conditions by showing that the “mass” is of water attenuation and by demonstrating continuity with the superior pericardial recess at the level of the ascending aorta. The concave extension of the right lung into the mediastinum anterior to the spine is the azygoesophageal recess, which extends inferiorly from the subcarinal region to the level of the diaphragm.

E

Right Pulmonary Artery Level

FIG 38-3 Axial plane—aortic arch level. The superior vena cava (S) and aortic arch (ARCH) lie anterior to the trachea (T) and esophagus (E). The thymus, which has undergone fatty iniltration, is anterior to the arch.

The main pulmonary artery is anterior and to the left of the ascending aorta (Figs. 38-8 and 38-9). The right pulmonary artery extends posteriorly and to the right from the main pulmonary artery, passing anterior to the bronchus intermedius and posterior to the SVC. The right superior pulmonary vein is to the right of and lateral to the

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PART II CT and MR Imaging of the Whole Body

LPA

A

S

PA

A

TA LSPV RPA SPR D

AZE

D

LPA

FIG 38-6 Axial plane—left pulmonary artery level. To the left of the left

FIG 38-8 Axial plane—right pulmonary artery level. The main pulmo-

pulmonary artery (LPA) lie the left superior pulmonary veins. The ascending (A) and descending (D) aorta and superior vena cava maintain their relative positions from the level above. The truncus anterior (TA), or right upper lobe pulmonary artery, is anterior to the right upper lobe bronchus. The azygoesophageal recess (AZE) is a concavity anterior to the spine. The superior pericardial recess (SPR) is an extension of the pericardium.

nary artery (PA) divides into the left (LPA) and right (RPA) pulmonary arteries. The right pulmonary artery passes anterior to the right main bronchus, and the left pulmonary artery passes over the left main bronchus. A, ascending aorta; D, descending aorta; LSPV, left superior pulmonary vein; S, superior vena cava.

S

S A

MPA

A

LPA

LSPV RPA

D D

FIG 38-7 Axial plane—left pulmonary artery level. A, ascending aorta; D, descending aorta; LPA, left pulmonary artery; S, superior vena cava.

intrapulmonary portion of the right pulmonary artery. Anterior to the left main and upper lobe bronchi is the left superior pulmonary vein, and posterior to the left upper lobe bronchus is the left lower lobe pulmonary artery.

Left Atrial Level The anatomy of the mediastinum is complex at this level (Figs. 38-10 and 38-11). Anterior to the SVC is the right atrial appendage, curving laterally around the ascending aorta. The aorta is located centrally within the mediastinum, and anterior and to the left of the aorta is the pulmonary outlow tract. Posterolateral and to the left of the pulmonary outlow tract is the left atrial appendage. Within the fat between the left atrial appendage and the aortic root is the left main coronary artery. The left superior pulmonary vein enters the left atrium imme-

FIG 38-9 Axial plane—right pulmonary artery level. The main pulmonary artery (MPA) divides into the right pulmonary artery (RPA) and the left pulmonary artery, which is more superior and not visible. The left superior pulmonary vein (LSPV) is anterior to the left main bronchus, and the left pulmonary artery is posterior. A, ascending aorta; D, descending aorta; S, superior vena cava.

diately posterior to the left atrial appendage. The right superior pulmonary veins enter the left atrium just posterior to the SVC. The esophagus position at this level is variable and may be midline or to the right or left of midline along the posterior wall of the left atrium.

Four-Chamber Level All four chambers of the heart are identiied at this axial level (Figs. 38-12 and 38-13) and should not be confused with a four-chamber cardiac reconstructed image. The posteriorly located left atrium is the most cranial of all the chambers. The right and left inferior pulmonary

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RV RAP S

P

RA LV

A A LAP

LA

LA

RPA D

LPA

D

FIG 38-10 Axial plane—left atrial level. The left atrium (LA) is the most

FIG 38-12 Axial plane—four-chamber level. A, aortic root; D, descend-

superior and posterior chamber of the heart. Superior pulmonary veins enter the anterosuperior portion of the left atrium. The left atrial appendage (LAP) is situated anterior and to the left of the left atrium, adjacent to the main pulmonary artery (P). The right atrial appendage (RAP) is anterior to the superior vena cava (S) and adjacent to the ascending aorta (A). D, descending aorta; LPA, left pulmonary artery; RPA, right pulmonary artery.

ing aorta; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

R

LAD RV

RA

C A

LA

IPV

RPA D LPA

FIG 38-13 Axial plane—calciied coronary arteries at the four-chamber FIG 38-11 Axial plane—left atrial level. A, aortic root; D, descending aorta; IPV, left inferior pulmonary vein; LA, left atrium; LPA, left lower lobe pulmonary arteries; RA, right atrium; RPA, right lower lobe pulmonary artery; RV, right ventricle.

veins enter the posterolateral aspect of the left atrium. Anterior and to the right is the right atrium. To the left and anterior to the right atrium is the right ventricle, located behind the sternum. The left ventricle is to the left and posterior to the right ventricle. The coronary arteries can be detected if they are calciied or if there is fat surrounding the heart. The right coronary artery lies in the right atrioventricular groove. The circumlex coronary artery lies in the left atrioventricular groove, and the left anterior descending coronary artery lies in the interventricular groove between the left and right ventricles.

level. C, circumlex coronary artery; LAD, left anterior descending coronary artery; R, right coronary artery.

Three-Chamber Level The ventricles and right atrium are identiied at this level (Fig. 38-14); the left atrium, because of its more cranial position, is not visible. The right atrium is located to the right. To the left and anteriorly, the thinwalled right ventricle is located just beneath the sternum. The thickwalled left ventricle makes up the posterolateral left portion of the mediastinum. Between the left ventricle and the inferior vena cava’s (IVC’s) opening into the right atrium is the coronary sinus.

Coronal and Sagittal Planes As CT imaging and workstation technologies have advanced, the use of multiplanar imaging reconstructions for interpretation has become routine. It is important for radiologists to recognize the normal

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BC

RV LV

RA

RV

LCC A

S P

I CS D AZ

LV

FIG 38-14 Axial plane—three-chamber level. The left atrium is more cranial to this level and not visible. The three visualized chambers are the right atrium (RA), right ventricle (RV), and left ventricle (LV). The coronary sinus (CS) is between the inferior vena cava (I) and the left ventricle. AZ, azygos vein; D, descending aorta.

FIG 38-16 Coronal plane—ascending aorta level. A, aorta; BC, brachiocephalic artery; LCC, left common carotid artery; LV, left ventricle; P, pulmonary artery; RV, right brachiocephalic vein; S, superior vena cava; T, trachea.

T RV LB

LCC A

S

A

P P

RAP

LA LV RA

LV

FIG 38-15 Coronal plane—aortic outlow tract level. A, aorta; LB, left

FIG 38-17 Coronal plane—pulmonary artery level. A, aorta; LA, left

brachiocephalic vein; LV, left ventricle; P, pulmonary artery; RA, right atrium; RAP, right atrial appendage.

atrium; LCC, left common carotid artery; LV, left ventricle; P, pulmonary artery; RV, right brachiocephalic vein; S, superior vena cava; T, trachea.

mediastinal anatomy in the coronal and sagittal planes. Given the long axis of several structures in the mediastinum, axial and sagittal planes are particularly useful when assessing the aorta, great vessels, vena cava, trachea, esophagus, and heart. Coronal (Figs. 38-15 to 38-19) and sagittal (Figs. 38-20 to 38-24) reformations at different levels are provided for correlation. The same nomenclature as in the axial plane is used, along with the same abbreviations to identify the different structures.

anatomic regions or compartments is still important, it is not essential, because CT and magnetic resonance imaging (MRI) can accurately localize and in many instances characterize masses. Despite these advances, however, mediastinal masses are still discussed, classiied, and grouped by their position on chest radiographs. In this chapter we use the widely accepted division of the mediastinum into superior, anterior, middle, and posterior compartments. The superior mediastinum is the space between the thoracic inlet and the superior aspect of the aortic arch (i.e., all mediastinal structures above an imaginary line drawn between the sternal angle and the fourth intervertebral disk on the lateral chest radiograph). The anterior mediastinum is the space anterior to the heart and great vessels on the lateral chest radiograph. It is bordered anteriorly by the sternum and posteriorly by the pericardium. Using this designation, normal

Mediastinal Divisions The mediastinum extends craniocaudad from the thoracic inlet to the diaphragm, and historically it has been divided into compartments (on the chest radiograph) to facilitate lesion localization and aid in the differential diagnosis. Although this division of the mediastinum into

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LSC RV A

T

LPA

RAP S

RPA LA

RPA RA

FIG 38-18 Coronal plane—left atrial level. A, aorta; LA, left atrium; LPA, left pulmonary artery; LSC, left subclavian artery; RPA, right pulmonary artery; T, trachea.

FIG 38-20 Sagittal plane—superior vena cava level. RA, right atrium; RAP, right atrial appendage; RPA, right pulmonary artery; RV, right brachiocephalic vein; S, superior vena cava.

A

T

A

D

RPA

AZ

LA

FIG 38-19 Coronal plane—descending aorta level. A, aortic arch; D, descending aorta.

anterior mediastinal structures include the thymus, branches of the internal mammary artery and vein, lymph nodes, and fat. There is controversy concerning the division between the middle and posterior mediastinum. Some authors believe the dividing line should be the posterior aspect of the pericardium, whereas others divide the two by an imaginary line drawn 1 cm posterior to the anterior border of the vertebral bodies. The latter method places most aortic and esophageal lesions in the middle mediastinum and reserves the posterior mediastinum for neurogenic or other paraspinal lesions. Other methods divide the middle and posterior mediastinum based on the azygos arch and aorta. For purposes of this discussion, we deine the middle mediastinum as the space between the anterior border of the pericardium and an imaginary line drawn 1 cm posterior to the anterior border of the vertebral bodies on the lateral radiograph. As such, it contains the heart, aorta, SVC, IVC, brachiocephalic arteries and veins, pulmonary

RA

FIG 38-21 Sagittal plane—right atrial level. A, ascending aorta; AZ, azygos vein; LA, left atrium; RA, right atrium; RPA, right pulmonary artery; T, trachea.

arteries and veins, thoracic duct, azygos and hemiazygos veins, phrenic and vagus nerves, trachea and proximal bronchi, esophagus, mediastinal fat, and lymph nodes. The posterior mediastinum is deined as the space between the imaginary line drawn 1 cm posterior to the anterior border of the vertebral bodies and the posterior paravertebral gutters. Structures in the posterior mediastinum thus include nerves, fat, vertebral column, and lymph nodes.

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BC T

LPA

RPA A LA RV

RV

LV

D

FIG 38-22 Sagittal plane—aortic outlow tract level. A, ascending aorta; BC, brachiocephalic artery; D, descending aorta; LA, left atrium; RPA, right pulmonary artery; RV, right ventricle; T, trachea.

LCC

LSC A

P

AT

LA

RV D

FIG 38-23 Sagittal plane—pulmonary artery outlow tract level. A, ascending aorta; AT, aortic outlow tract; D, descending aorta; LA, left atrium; LCC, left common carotid artery; LSC, left subclavian artery; P, pulmonary artery (outlow tract); RV, right ventricle.

IMAGING TECHNIQUES Computed Tomography Although the chest radiograph is usually the initial study that reveals a mediastinal abnormality, CT is used to assess the location and extent of mediastinal disease; because of its superior contrast resolution, it is also used to characterize the tissue components of masses (Fig. 38-25).

FIG 38-24 Sagittal plane—left ventricular level. LPA, left pulmonary artery; LV, left ventricle; RV, right ventricle.

CT is useful for distinguishing vascular variants or benign processes of the mediastinum (e.g., lipomatosis) from true pathologic conditions. Although CT is usually used to further evaluate an abnormality detected on the chest radiograph, in certain clinical situations CT may be performed when the chest radiograph is normal, such as in patients with myasthenia gravis, owing to the strong association between that disease and thymoma (Fig. 38-26). Also, certain malignancies such as lung cancer have a marked predilection to metastasize to mediastinal lymph nodes. Because these lymph node metastases may not be visible on chest radiographs, CT is used by most thoracic surgeons and oncologists to assess the mediastinal nodes in patients with lung cancer. Recent advances in CT imaging, such as multidetector and dualsource technologies, have improved its ability to image the mediastinum. Signiicant shortening of scanning time limits respiratory and cardiac motion artifacts, and in some instances the total dose of iodinated contrast material can be reduced. Dual-energy CT applications for imaging the mediastinum are not yet well established but may be helpful in quantifying perfusion, a potentially helpful marker in differentiating benign from malignant processes.182 Volumetric CT data sets can be effectively reconstructed in a variety of nonaxial planes, often facilitating interpretation of mediastinal abnormalities. Application of nonaxial two- and three-dimensional (2D and 3D) reconstruction techniques has proved most useful for imaging abnormalities of the central airways and great vessels (Figs. 38-27 and 38-28). For example, in the evaluation of stenoses in obliquely oriented bronchi, these reconstruction techniques can improve diagnostic accuracy and conidence in the interpretation. It should be emphasized, however, that axial CT images are usually suficient for diagnosis. Nevertheless, because 2D and 3D images present anatomic information in a context more familiar to clinicians, these methods may demonstrate the location and extent of an abnormality in a way that radiologic reports and axial CT images often do not and can be helpful in treatment planning. Most routine CT scans of the mediastinum can be performed without intravenous (IV) contrast enhancement unless the primary

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* A

*

A

B FIG 38-25 Coronary artery pseudoaneurysm post ascending aortic repair. A, Posteroanterior chest radiograph shows a mediastinal mass (arrows) superimposed on the right heart border and hilum. B, Contrastenhanced CT demonstrates the mass to represent a large pseudoaneurysm (arrows) with marginal thrombus (asterisks) arising from the right coronary artery anastomosis with the ascending aortic graft (A). Descending aortic dissection (arrowhead) is also present. A, ascending aortic graft.

S A

FIG 38-26 Thymoma in a woman with myasthenia gravis. The chest radiograph (not shown) was normal. Because of the association between myasthenia gravis and thymoma, contrast-enhanced chest CT was performed, revealing a small soft tissue mass in the anterior mediastinum (arrow). Resection conirmed thymoma. A, aorta; S, superior vena cava.

indication is a suspected vascular abnormality (Fig. 38-29). Interpretation of non–contrast-enhanced (NCE) CT scans can be more dificult and time-consuming than interpretation of contrast-enhanced scans and requires a thorough knowledge of mediastinal anatomy and normal variants. There are, however, several advantages to NCE CT: (1) scan time is decreased because there is no need to establish IV access, set up the contrast injector, or delay the scan as the bolus is administered; (2) there is no risk of contrast reaction; and (3) the cost is lower. When needed, IV contrast is given through a large forearm or antecubital vein using a power injector. The contrast injection rate and total injection volume depend on the indication. For routine purposes a rate of 3 mL/sec for a total volume of 100 mL is suficient. For vascular imaging (aorta and pulmonary artery), higher injection rates (4-6 mL/sec) are often necessary. In such cases, injection through a relatively large-bore IV catheter (18 or 20 gauge) into a large antecubital vein is mandatory. Timing of the bolus in relationship to the scan also varies and depends on both the indication (routine vs. arterial imaging) and the time required to complete the scan. CT is usually performed without esophageal contrast; however, oral contrast can be helpful in identifying the relationship between the esophagus and other mediastinal structures and occasionally in depicting intrinsic esophageal abnormalities (Fig. 38-30). Commercial preparations of esophageal paste made of a dilute barium mixture are available. The patient must swallow several teaspoons of the paste and refrain from further swallowing during the examination. CT scans of the mediastinum are usually reconstructed and interpreted in an axial format. Until recently, sagittal, coronal, and off-axis reconstructions of the thorax were not routinely performed because of slice misregistration and respiratory motion artifacts. However, with

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PART II CT and MR Imaging of the Whole Body S T

R R

L

U

L M

L

D

B

A

FIG 38-27 Fibrosing mediastinitis. A, Axial CT shows marked narrowing of the bronchus intermedius (arrowhead) by a soft tissue attenuation mass (M, arrows). Note the extensive subcarinal calciication. B, Volumerendered shaded-surface display shows long-segment irregular narrowing of the bronchus intermedius (arrowheads). 3D reconstructions can facilitate assessment and treatment of airway stenoses. D, descending aorta; L, left main bronchus; R, right main bronchus; S, superior vena cava; T, trachea; U, right upper lobe bronchus.

A

B FIG 38-28 Traumatic aortic pseudoaneurysm. A, Axial contrast-enhanced CT demonstrates a focal contour abnormality of the medial aortic arch (arrow). B, Volume surface-rendered reconstruction in a posterior coronal plane better demonstrates the three-dimensional nature of the pseudoaneurysm (arrow) and its relationship to other anatomic structures. 3D reconstructions of CT angiograms display anatomy in a more familiar perspective to clinicians than do axial CT images.

the advent of multiplanar scanning, continuous volume data sets can be acquired during a single breath hold, and excellent nonaxial 2D and 3D reconstructed images of mediastinal vascular structures and airways can be generated (see Figs. 38-3 and 38-4). The different reconstruction methods, such as multiplanar reformat imaging, multiplanar volume reformat imaging, and external and internal 3D renderings, vary signiicantly in computational complexity and time required to generate the images.

Interpretation of mediastinal CT images is most commonly performed at a PACS (picture archiving and communication system) or workstation that permits dynamic adjustment of window and level settings for thorough assessment of the mediastinum; a wide range of attenuation values (−800 Hounsield units [HU] for lung, 600 HU for bone) are encountered. Appropriate image settings are essential for accurate depiction of air, fat, luid, calciication, IV contrast, and bone. If hard-copy (ilm) format is used, care should be taken to ensure

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adequate window and level settings are used. When ilming CT studies of the chest, lung settings should have a wide width to encompass airilled lung and soft tissue and are usually viewed at a level of −600 and a width of 1200. Because of the smaller density range among fat, soft tissue, bone, and contrast-enhanced vessels, mediastinal settings are usually viewed at a level of 50 and a width of 350. These levels and widths can be varied to aid in evaluation of any lesion that cannot be adequately differentiated on standard settings. Bone windows, with a wide width and a level of near 400 HU, are often needed to evaluate for possible bone metastases.

Magnetic Resonance Imaging

A

*

Although CT imaging usually provides the requisite information in most patients with mediastinal abnormalities, MRI, because of its multiplanar capability and high contrast resolution, is occasionally used to evaluate the location and extent of disease. MRI is the modality of choice for imaging neurogenic tumors, because it not only demonstrates the number and nature of the lesions but also depicts intraspinal extension. Additionally MRI is useful in conirming the cystic nature of mediastinal lesions that appear solid on CT (Fig. 38-31) and demonstrating vascular structures in patients in whom use of iodinated IV contrast is contraindicated (Fig. 38-32). The role of MRI in characterizing mediastinal pathology is evolving, with recent literature suggesting potential applications in differentiating benign from malignant nodal and thymic disease. Two potential disadvantages of MRI of mediastinal abnormalities, compared with CT, are its poor demonstration of calciication and comparatively poor spatial resolution.

Positron Emission Tomography

B

C FIG 38-29 Pseudoaneurysm of the proximal descending aorta. A, Posteroanterior chest radiograph shows a soft tissue mass (arrowheads) superimposed on the left hemithorax, with preserved arch and descending aortic interfaces. B, Noncontrast chest CT was performed, revealing a homogeneous mass (asterisk) of the middle and anterior mediastina. Percutaneous biopsy was requested by the primary care team for tissue diagnosis. C, In lieu of biopsy, a contrast-enhanced CT was performed, revealing the mass to represent a large pseudoaneurysm (arrows) arising at the isthmus of the proximal descending thoracic aorta.

Whereas CT and MRI provide morphologic information, positron emission tomography (PET) and integrated PET/CT provide important functional information in the evaluation and management of mediastinal disease. Several studies have shown the value of luorine-18 luorodeoxyglucose (18F FDG) PET in differentiating benign from malignant mediastinal masses. FDG uptake is associated with thymoma, thymic carcinoma, carcinoid, lymphoma, esophageal carcinoma, and metastatic disease among other entities. Of particular interest in oncologic imaging is the identiication of mediastinal nodal disease for staging purposes, which affects treatment decisions and potential resectability of the primary tumor. On CT, lymph node size is the primary determinant of disease, with a short-axis dimension greater than 1 cm indicative of pathology. Unfortunately, metastatic involvement can be associated with normal-sized lymph nodes and go undetected at CT imaging. FDG PET, however, is highly sensitive and speciic for detection of nodal disease relative to CT alone. Accuracy, sensitivity and speciicity improves even more when PET is performed in conjunction with CT (PET/CT). Furthermore, PET is superior to CT in detecting distant metastases, which has been shown to improve staging accuracy and reduce futile treatments. FDG PET also plays an important role in monitoring treatment response following initiation of therapy. PET has also been found to provide prognostic information in certain mediastinal pathology; for example, a negative PET obtained following treatment for lymphoma is associated with a lower risk of recurrent disease and longer progression-free survival than in patients with a positive posttreatment PET examination. Although PET is primarily used in the evaluation of suspected malignancy, FDG uptake can also be associated with infectious and inlammatory conditions of the mediastinum, such as acute mediastinitis or sarcoidosis. Examples of the utility of FDG PET in the

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PART II CT and MR Imaging of the Whole Body

L

M

* M

A

A

A

B FIG 38-30 Esophageal leiomyoma. A, CT shows a large middle mediastinal mass with focal punctate calciications (arrowheads). Note displacement of the esophagus anteriorly (arrow). The CT appearance is nonspeciic, and the origin of the mass is uncertain. A, aorta; L, liver; M, mass. B, CT following oral ingestion of barium reveals distortion of the esophageal lumen (asterisk), consistent with a mass (M) arising within the wall of the esophagus. Resection conirmed leiomyoma.

P P A

A

A

B

C FIG 38-31 Mediastinal cyst. A, CT shows a well-circumscribed homogeneous mass in the anterior mediastinum (arrowheads). Although of lower attenuation than vascular structures, the appearance is not diagnostic for mediastinal cyst. A, ascending aorta; P, main pulmonary artery. B and C, Axial T1- and T2-weighted MRIs show the mass to be of homogeneous low signal intensity on the T1-weighted image (arrowheads in B) and high signal intensity on the T2-weighted image (C), consistent with a cyst.

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Mediastinal Abnormalities by Compartment TABLE 38-1

A

D

Location

Lesion

Superior mediastinum Anterior mediastinum

Thyroid goiter, tortuous great vessels Thymic lesions, germ cell tumors, parathyroid adenoma, lymphatic malformations, hemangioma Esophageal lesions, airway lesions, foregut cysts, pericardial cysts Neurogenic tumors, paraspinal abscess, extramedullary hematopoiesis Mediastinitis, lipomatosis, lymphadenopathy (lymphoma, metastases, Castleman’s disease, infection), mesenchymal tumors, vascular abnormalities and anomalies, diaphragmatic hernias

Middle mediastinum Posterior mediastinum Multiple compartments

A

A

D

P

B FIG 38-32 Non-Hodgkin’s lymphoma in a patient with renal insuficiency. A, CT shows a homogeneous middle and posterior mediastinal mass encasing the descending aorta (D), anteriorly displacing the tracheal carina (arrows) and extending into the paravertebral region bilaterally (arrowheads). Note small bilateral pleural effusions. A, ascending aorta. B, Cine gradient-recalled echo MRI performed to evaluate possible vascular invasion conirms low within the descending aorta (D). Note the low-signal-intensity mass (arrowheads) and the high-signalintensity pleural effusion (P). A, ascending aorta.

evaluation of mediastinal processes are provided in reference to speciic disease entities throughout this chapter.

MEDIASTINAL ABNORMALITIES A useful approach for discussing mediastinal abnormalities is to classify them into processes that predominantly affect speciic compartments (superior, anterior, middle, or posterior) and those that can affect multiple compartments (Table 38-1).

Superior Mediastinal Abnormalities Common superior mediastinal abnormalities include intrathoracic extension of thyroid goiters or masses and tortuous great vessels.

Thyroid Goiter20,102,109,129,131,237,305 On CT the normal thyroid gland is typically visible at or just below the level of the cricoid cartilage (Fig. 38-33A). It appears on NCE CT

as two wedge-shaped structures of homogeneous attenuation on either side of the trachea, separated by a narrow anterior isthmus. It typically enhances homogeneously following administration of IV contrast. On MRI T1-weighted images the normal thyroid gland usually has intermediate signal intensity, slightly greater than that of adjacent muscle, and on T2-weighted images it has higher signal intensity (see Fig. 38-33B). Most thyroid masses in the mediastinum are caused by intrathoracic extension of thyroid goiters; these account for up to 10% of mediastinal masses resected at thoracotomy. True ectopic thyroid masses in the mediastinum are rare. Typically a thyroid goiter extends into the thyropericardiac space anterior to the recurrent laryngeal nerve and brachiocephalic vessels, although posterior extension adjacent to the trachea occurs in 20% of cases. Rarely a thyroid mass extends behind the esophagus and presents as a posterior mediastinal mass. A mediastinal goiter is usually detected on chest radiographs as a thoracic inlet or superior mediastinal mass that deviates and occasionally narrows the trachea. Although scintigraphy can detect mediastinal goiters, uptake of technetium or iodine is variable and may not be visible. The CT appearance of a mediastinal goiter is variable, but it can be conidently diagnosed when lesion continuity with the thyroid gland is visible. Additional useful features to establish the diagnosis are heterogeneous attenuation with areas of both high and low attenuation on NCE scans, marked enhancement following administration of IV contrast, and focal punctate or curvilinear calciications (Figs. 38-34 and 38-35). The cystic and adenomatoid composition of goiters results in a heterogeneous appearance on both T1- and T2-weighted MRIs (Fig. 38-36). On T1-weighted images goiters may have a lower signal intensity than normal thyroid, but high signal intensity may be seen in areas of subacute hemorrhage, colloid cysts, and adenomas. Goiters have high signal intensity on T2-weighted images.

Tortuous Great Vessels Tortuosity of the great vessels is a common cause of superior mediastinal abnormality on chest radiographs. The most common location of the radiographic abnormality is in the right paratracheal region; this is true because in older patients the right brachiocephalic artery often has a tortuous course before giving rise to the right subclavian and common carotid arteries. NCE CT can often determine that tortuous vessels are the cause of the apparent mass. Calciication within vessel

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FIG 38-33 Normal thyroid gland. A, Contrast CT shows the typical appearance of the thyroid gland (arrows). Note the homogeneous enhancement. T, trachea. B, T1-weighted axial MRI shows homogeneous intermediate signal intensity, typical of a normal thyroid gland (arrows). T, trachea.

walls allows conident identiication of tortuous arteries. If any doubt exists as to the vascular nature of the mass, IV contrast enhancement readily identiies the vessels (Fig. 38-37).

Anterior Mediastinal Abnormalities38,52,325,339,353 Approximately half of all mediastinal masses occur in the anterior mediastinum. Lesions that occur preferentially in the anterior mediastinum include thymic lesions (cysts, thymolipoma, thymoma, thymic carcinoma), germ cell tumors, parathyroid adenoma, lymphatic malformations, and hemangioma. Lymphoma is another common cause of an anterior mediastinal mass, but it is discussed in the section on diffuse mediastinal disease.

Thymic Lesions225,250,327 Normal thymus.17,64,87,92,100,237,246,318,355 The thymus is a bilobed triangular gland that occupies the thyropericardiac space of the anterior mediastinum and extends inferiorly to the heart. The normal morphology and size of the thymus change markedly with age. There is wide variation in the normal size of the thymus, particularly in children and young adults. In newborns the thymus gland is often larger than the heart. Thymic size decreases with age as the gland undergoes fatty iniltration. An atrophied thymus is often visualized on CT in patients in the fourth decade of life but is seen in less than 50% of patients older than 40 years (Fig. 38-38). The most useful measurement is the thickness of the lobes, measured perpendicular to the long axis of the gland. The normal maximal thickness before age 20 is 18 mm; it is 13 mm in older individuals. Although these measurements are useful indicators of thymic abnormality, thymic shape is also important; focal contour abnormality of the normal thymus gland suggests an underlying abnormality. On CT the normal thymus appears as a homogeneous bilobed structure of soft tissue attenuation in the anterior mediastinum (Fig. 38-39). It is usually seen at the level of the aortic arch and the origin of the great vessels. The left lobe is usually slightly larger than the right. Rarely a lobe is congenitally absent. The normal thymus is easily demonstrated on MRI (Fig. 38-40). Characteristically the thymus is homogeneous with intermediate signal intensity (less than that of fat) on T1-weighted images. Because the thymus begins to involute at puberty and is replaced by fat in older patients, the T1-weighted signal intensity of the thymus increases with age. On T2-weighted images the thymus has high signal intensity similar to fat in all age groups; this can make

identiication of the thymus dificult in patients with abundant mediastinal fat. The normal thymus in patients younger than 20 years typically has diffuse increased FDG uptake on PET. After that age, signiicant FDG accumulation is less common. Nevertheless, signiicant FDG uptake in the thymus, sometimes simulating that seen in malignancy, is occasionally seen in adults (see Fig. 38-39). A standardized uptake value (SUV) of less than 3.1 is typical for normal thymic tissue, whereas SUV greater than 3.4 is suspicious for malignancy. Thymic masses may sometimes be dificult to distinguish from normal thymus. As a rule, however, thymic masses usually manifest on CT or MRI as round masses and do not conform to the shape of the normal thymus. In addition, thymic masses are usually of heterogeneous attenuation on CT, with areas of decreased attenuation and possibly calciication. Thymic hyperplasia.3,22,76,103,121,137,148,195,196 Thymic hyperplasia can occur in association with hyperthyroidism, acromegaly, Addison’s disease, or stress, as well as in patients receiving chemotherapy or radiation therapy and in those with myasthenia gravis. Differentiating between hyperplasia and other causes of thymic enlargement on CT can be dificult because there are no speciic attenuation characteristics associated with hyperplasia. Because thymic rebound or hyperplasia occurs in patients after chemotherapy or radiation therapy, it can be dificult to distinguish this enlargement from recurrent tumor. Generally, however, the thymus in rebound hyperplasia has a normal shape, with homogeneous attenuation on CT (Figs. 38-41 and 38-42). Asymmetry of the lobes, focal contour abnormalities, and heterogeneity suggest tumor. MRI may be beneicial in distinguishing normal thymus and thymic hyperplasia from thymic neoplasms. Unlike thymic tumors, normal and hyperplastic thymic tissue suppresses on out-of-phase gradient echo imaging because of the presence of interspersed microscopic fat. In addition, thymic rebound or hyperplasia is typically of homogeneous normal intensity on MRI, whereas tumors demonstrate more heterogeneous signal properties and enhancement. Preliminary data suggest that FDG PET imaging may be helpful for differentiating thymic hyperplasia from thymoma in patients with myasthenia gravis. Patients with thymic hyperplasia show homogeneous FDG accumulation in the thymus (see Fig. 38-42), whereas patients with thymoma tend to have more focal FDG uptake. The degree of uptake tends to be greater in thymoma than in thymic hyperplasia.

CHAPTER 38

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B FIG 38-34 Thyroid goiter. A, CT shows a heterogeneous superior mediastinal mass (arrowheads) with punctate calciication. Images at the thoracic inlet (not shown) conirmed the mass’s contiguity with the left thyroid lobe, consistent with an intrathoracic extension of goiter. T, trachea. B, Contrast CT shows heterogeneous enhancement of the mass. T, trachea.

B FIG 38-35 Mediastinal goiter. A, Contrast CT in the axial plane shows a large goiter (G) displacing the trachea (T) to the right and displacing the left common carotid (LCC) and left subclavian arteries (LSC) to the left. Note the heterogeneous enhancement and calciication. B, In a different patient, contrast CT in the coronal plane shows intrathoracic extension of a goiter (G) and rightward displacement of the trachea (T). Note heterogeneous enhancement and calciication. A, aorta.

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FIG 38-36 Mediastinal goiter. Coronal MRI shows mediastinal thyroid tissue (T) on both sides of the trachea. The trachea is deviated to the right at the thoracic inlet.

Thymic cyst.3,18,51,62,115,139,146,195,219,298,325,331 Thymic cysts account for approximately 3% of all anterior mediastinal masses and are either congenital or secondary to inlammation or malignancy. Congenital thymic cysts most likely arise from remnants of the thymopharyngeal duct and are usually thin-walled unilocular lesions less than 6 cm in diameter. On CT they are homogeneous, of water attenuation, with very thin or imperceptible walls. On MRI they manifest as well-circumscribed anterior mediastinal masses of high signal intensity on T2-weighted images. Signal intensity usually increases with increasing repetition time (TR). Occasionally, thymic cysts appear as solid masses on CT because they are illed with proteinaceous luid. In these cases, MRI can be useful to conirm the cystic nature of the lesion (Fig. 38-43). Acquired thymic cysts occur in the setting of inlammation (e.g., Sjögren’s syndrome, aplastic anemia, myasthenia gravis) or malignancy. Associated malignancies include Hodgkin’s lymphoma, seminoma, thymoma, and thymic carcinoma (Fig. 38-44). These cysts usually have walls of variable thickness, are multilocular, and range in size from 3 to 17 cm in diameter. These cysts can contain hemorrhage or calciication. As such, the CT and MRI features of acquired thymic cysts are more variable than those of congenital thymic cysts. Because of their association with thymic neoplasia, care must be taken when interpreting cystic lesions of the anterior mediastinum. If a thymic cyst is multilocular, heterogeneous, thick walled, or associated with a soft tissue component, it must be evaluated further (biopsy or resection) to exclude malignancy (see Fig. 38-44). Furthermore, multiloculated thymic cysts can exhibit FDG uptake on PET/CT, although typically less than that of thymoma or thymic carcinoma (Fig. 38-45). Thymolipoma.195,223,287,311,358 Thymolipomas are rare, benign, slowly growing neoplasms of the anterior mediastinum that can simulate cardiomegaly on the chest radiograph. They occur with equal incidence in men and women, and although there is a wide age range at presentation, most are diagnosed in young adults. On CT these masses are typically large and heterogeneous with a mixture of fat elements and soft tissue attenuation, conforming to adjacent structures. They are not locally invasive, although compression of adjacent structures occurs in approximately 50% of patients. Because they consist of fat

and residual thymic tissue, thymolipomas usually have high signal intensity (similar to fat) with interspersed areas of intermediate signal intensity on both T1- and T2-weighted MRIs. Thymic epithelial neoplasms.* The classiication of thymic epithelial neoplasms is continuing to evolve. According to the traditional classiication, neoplasms of the thymus were termed thymoma, invasive thymoma, and thymic carcinoma. However, in the most recent 2004 World Health Organization (WHO) classiication, they are designated thymoma (subtypes A and B) and thymic carcinoma. There are inherent problems with the WHO classiication, including poor inter- and intraobserver reproducibility and inconsistencies between histologic grade and clinical outcomes. Despite these limitations, the WHO histologic subtype classiication reportedly closely correlates with the clinicopathologic staging classiication of thymomas devised by Masaoka and coworkers.205,168 The Masaoka-Koga staging system is most widely used today and is based on the presence of capsular invasion: Stage I: macroscopically encapsulated Stage IIa: microscopic capsular invasion Stage IIb: macroscopic invasion into surrounding fatty tissue of mediastinal pleura Stage III: macroscopic invasion into a neighboring organ Stage IVa: pleural or pericardial dissemination Stage IVb: lymphatic or hematogenous metastasis More recently, Suster and Moran proposed that thymic neoplasms be classiied as well-differentiated (WHO thymoma types A, AB, B1, and B2), moderately-differentiated (WHO thymoma type B3), and poorlydifferentiated thymic carcinoma (WHO thymic carcinoma).329,330 Owing to the complexities of histopathologic classiication and the lack of correlation with prognosis, the treatment of thymic epithelial tumors is primarily based upon clinical staging and completeness of surgical resection. These two variables have been found to best correlate with progression-free and overall survival. Thymoma. Thymomas (well- and moderately-differentiated thymic carcinoma or thymoma types A, AB, B1, B2, and B3 in the WHO classiication) account for approximately 20% of all mediastinal tumors and are the most common primary tumor of the anterior mediastinum. Seventy-ive percent of thymomas occur in the anterior mediastinum, 15% occur in both the anterior and superior mediastina, and 6% occur in the superior mediastinum. Another 4% occur ectopically, with the posterior mediastinum being the least common location. Although thymomas can occur in children, most patients are older than 40 years at presentation; 70% of affected patients present in the ifth and sixth decades of life. There is an equal incidence in men and women. Most affected patients are asymptomatic at presentation, with the lesion detected on routine chest radiographs. Chest pain, cough, and symptoms related to compression of adjacent structures occur in approximately 33% of patients. Paraneoplastic syndromes are common and include myasthenia gravis (50%), hypogammaglobulinemia (10%), and pure red cell aplasia (5%). Although up to 50% of patients with thymoma have myasthenia gravis, only 10% to 20% of patients with myasthenia gravis have a thymoma; 65% of these patients do, however, have lymphoid hyperplasia of the thymus. Because of the strong association between myasthenia gravis and thymoma, CT is often performed in patients with symptoms of myasthenia gravis even if the chest radiograph is normal. Text continued on p. 1042

*References 1, 3, 25, 77, 78, 80, 120, 147, 150, 168, 172, 193, 195, 202, 203, 205, 226, 231-233, 268, 286, 292, 294, 298, 325, 328-330, 336, 343, 354.

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Mediastinal Disease

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B FIG 38-37 Tortuous great vessels. A, Cone view from a posteroanterior chest radiograph shows a masslike opacity along the right superior mediastinum (arrow). B, Noncontrast CT shows tortuous right brachiocephalic and subclavian arteries (arrows) causing a right paratracheal mass. A, aorta.

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B FIG 38-38 Thymus gland in a 42-year-old woman with breast carcinoma. A, Contrast CT shows fatty replacement of the thymus gland. Residual thymic tissue manifests as linear areas of soft tissue in anterior mediastinal fat (arrow). A, aorta; S, superior vena cava. B, Noncontrast CT 6 months after bone marrow transplantation shows increased soft tissue in the anterior mediastinum, consistent with thymic hyperplasia (arrow). A, aorta; S, superior vena cava.

A

B FIG 38-39 Normal thymus in a 20-year-old man. A and B, Contrast-enhanced PET/CT shows soft tissue (arrows) in the anterior mediastinum that conforms to the normal shape of the thymus gland. Note homogeneous FDG uptake in normal thymic tissue.

CHAPTER 38

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FIG 38-40 Normal thymus in a 9-month-old child with coarctation of the aorta. Axial T1-weighted MRI shows the thymus gland (arrowheads) in the mediastinum, anterior to the aorta (A), with homogeneous intermediate signal intensity less than that of fat. Note the aortic coarctation (arrow). S, superior vena cava. (Case courtesy Donald Frush, MD, Duke University Medical Center, Durham, NC.)

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B FIG 38-41 Thymic rebound. A, CT at the time of chemotherapy shows thymus (T) is small. B, CT after cessation of chemotherapy shows thymus (T) has increased in size.

A SVC

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B FIG 38-42 Thymic hyperplasia in a young patient with chest pain. A, Contrast-enhanced CT demonstrates a prominent thymus without a discrete mass. A, aorta; P, pulmonary artery; SVC, superior vena cava. B, PET/ CT shows homogeneous FDG uptake within the thymus.

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C FIG 38-43 Congenital thymic cyst. A, Contrast CT shows a homogeneous water-attenuation cyst (asterisk) in the anterior mediastinum. Note absence of perceptible walls and a residual right thymic lobe (arrow). S, superior vena cava; T, trachea; TA, transverse aorta. B and C, MRIs obtained more caudally show that the mass (arrowheads) is homogeneous and of low signal intensity on the T1-weighted image (B) and of high signal intensity on the T2-weighted image (C). This appearance is typical of a cyst. A, ascending aorta; P, main pulmonary artery.

CHAPTER 38

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FIG 38-44 Seminoma associated with a thymic cyst. A, Contrast CT shows a well-circumscribed waterattenuation mass in the anterior mediastinum. Note the thin but perceptible wall (arrowheads). B, A more cephalic image reveals the soft tissue component of the mass (arrow). Resection revealed seminoma. T, trachea.

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D FIG 38-45 Acquired multilocular thymic cyst in an asymptomatic 64-year-old man who presented with an anterior mediastinal mass noted on a preoperative chest radiograph. A and B, Axial CT images demonstrate a complex multicystic mass in the anterior mediastinum. C and D, Axial PET/CT shows increased FDG uptake within the cyst walls.

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B FIG 38-46 Thymoma in a patient with myasthenia gravis. A, Posteroanterior chest radiograph shows a mass in the right cardiophrenic angle (arrowheads). B, Contrast-enhanced CT conirms a well-circumscribed heterogeneous cardiophrenic angle mass (arrowheads). Resection revealed thymoma.

Thymomas are typically well-marginated smooth or lobulated mediastinal masses, 5 to 10 cm in diameter, that characteristically arise from one lobe of the thymus. They are usually located anterior to the aortic arch but can occur in the cardiophrenic angle (Fig. 38-46). Most lesions are homogeneous, but necrosis and hemorrhage occur in up to one third. On CT or MRI, thymomas most commonly manifest as smooth or lobulated masses that distort the normal contour of the thymus (Fig. 38-47). They are typically unilateral masses, although bilateral mediastinal involvement can occur. On CT they can manifest as homogeneous or heterogeneous soft tissue–attenuation masses. Intratumoral cysts or areas of necrosis may be seen. Enhancement following IV administration of contrast is variable. Calciication, seen in up to 7% of cases, is usually thin and linear and located in the capsule. On MRI, thymomas manifest with low to intermediate signal intensity (similar to skeletal muscle) on T1-weighted images and with high signal intensity on T2-weighted images. Because up to 33% of thymomas have focal areas of necrosis, hemorrhage, and cystic change, the masses may have heterogeneous signal intensity. MRI occasionally reveals ibrous septa within the masses. The role of MRI in evaluation of thymoma is evolving. Recent studies suggest that diffusion-weighted imaging (DWI) and apparent diffusion coeficient (ADC) values may be beneicial in differentiating low-grade thymomas from high-grade thymomas and thymic carcinomas. In addition to diagnosis, imaging plays an important role in thymoma staging. Patients with invasive thymoma (Masaoka-Koga stage III or greater) beneit from neoadjuvant chemotherapy. Imaging indings that suggest invasive thymoma on CT or MRI include (1) tumor size 7 cm or greater, (2) lobulated contours, (3) poorly deined or iniltrative margins, (3) deinite vascular or chest wall invasion, (4) irregular interface with adjacent lung, and (5) evidence of spread to pleura (Figs. 38-48 to 38-50). Pleural spread manifests either as isolated pleural nodules (“drop metastases”) or as a contiguous pleural mass, often mimicking mesothelioma. Transdiaphragmatic spread may occur; hence, staging MRI or CT studies should include the upper abdomen. Pleural effusion is uncommon despite the often extensive

T

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B FIG 38-47 Thymoma in a patient with myasthenia gravis. A, Axial chest CT shows a well-circumscribed homogeneous anterior mediastinal mass (T). B, PET/CT depicts heterogeneous FDG uptake. Resection revealed thymoma.

CHAPTER 38 pleural metastases. Several CT and MRI indings are associated with a high rate of recurrence and metastasis as well as a poorer prognosis: tumor larger than 10 cm in diameter, with a lobulated or irregular contour; mediastinal fat or great vessel invasion; and pleural seeding. Typically, thymomas are FDG avid on PET/CT (see Fig. 38-47). Several recent studies have highlighted the potential use of FDG PET to differentiate noninvasive from invasive thymoma by the presence of conined uptake in the former and multiple discrete foci in the latter. Thymic carcinoma. Thymic carcinomas account for 20% of thymic tumors. They are aggressive malignancies that often exhibit marked local invasion and early dissemination to regional lymph nodes and distant sites. Distant metastases (lung, liver, brain, bone) are detected in 50% to 65% of patients at presentation. Typical histologies

A

FIG 38-48 Invasive thymoma in a patient with symptoms of superior vena cava obstruction. Axial T1-weighted MRI shows an iniltrative soft tissue mass (arrowheads) of intermediate signal intensity encasing the aorta (A) and extending into the superior vena cava (arrow). (From Erasmus JJ, et al: MR imaging of mediastinal masses. Magn Reson Imaging Clin N Am 8:59–89, 2000.)

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include squamous cell carcinoma and lymphoepithelioma-like carcinoma. Symptoms (chest pain, dyspnea, cough, SVC syndrome) are usually due to compression or invasion of adjacent structures; unlike with thymomas, paraneoplastic syndromes are rare. Radiologically, thymic carcinomas commonly manifest as large, poorly marginated, anterior mediastinal masses frequently associated with intrathoracic lymphadenopathy and pleural and pericardial effusions. Focal pleural implants are uncommon. On CT they are usually of heterogeneous attenuation and have poorly deined iniltrative margins (Fig. 38-51). On MRI they typically have intermediate signal intensity (slightly higher than that of skeletal muscle) on T1-weighted images and high signal intensity on T2-weighted images. Signal intensity may be heterogeneous because of hemorrhage and necrosis within the masses. MRI can be helpful for revealing local soft tissue and vascular invasion. The presence of an irregular contour, necrotic or cystic component, heterogeneous enhancement, lymphadenopathy, or great vessel invasion on CT or MRI is strongly suggestive of thymic carcinoma and frequently associated with a poor prognosis. Typically, thymic carcinoma exhibits signiicant FDG uptake on PET/CT that is usually higher than that in thymoma and thymic hyperplasia (Fig. 38-52). Neuroendocrine tumors of the thymus.25,38,39,117,165,166,261,285 Neuroendocrine tumors are uncommon lesions of the anterior mediastinum. These tumors have a varying malignant potential that ranges from relatively benign (thymic carcinoid) to highly malignant (small cell carcinoma of the thymus). Thymic carcinoid tumor is the most common of this group of tumors. Affected patients are typically in the fourth or ifth decade of life; there is a male predominance. Up to 50% of affected patients have hormonal abnormalities, and up to 35% have Cushing’s syndrome due to tumoral production of adrenocorticotropic hormone. Nonfunctioning thymic carcinoids may be seen in association with multiple endocrine neoplasia (MEN) syndrome type 1. Radiologically these tumors typically manifest as large masses with a propensity for local invasion. Focal areas of necrosis and punctate calciication may be present. On CT or MRI the masses are usually of heterogeneous attenuation or signal intensity, respectively (Fig. 38-53).

L Ao

B FIG 38-49 Invasive thymoma. A and B, Contrast CT shows a heterogeneous anterior mediastinal mass with focal areas of calciication. Note that the mass extends between the superior vena cava (asterisk) and the ascending aorta (Ao); there is contiguous extension to the hemidiaphragm (arrowheads). L, liver.

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B FIG 38-50 Invasive thymoma with pleural metastases. A, Contrast CT shows a lobular heterogeneous mass (arrowheads) in the anterior mediastinum. B, Noncontiguous pleural metastases (“drop metastases”; arrowheads) are present in the left hemithorax.

S

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A FIG 38-51 Thymic carcinoma. Contrast CT shows a heterogeneous mass in the anterior mediastinum. Low-attenuation regions are consistent with necrosis. A, aorta; S, superior vena cava.

FDG uptake by carcinoid tumors is variable, with a tendency to be low. However, increased uptake has been reported to correlate with aggressive behavior such as local invasion and distal metastases.81,115

Germ Cell Tumors66,183,191,192,248,249,288,325,339,347 Germ cell tumors (teratomas, seminomas, embryonal carcinomas, endodermal sinus tumors, and choriocarcinomas) are thought to arise from mediastinal remnants of embryonal cell migration. They constitute 10% to 15% of anterior mediastinal tumors. The mediastinum is the most common extragonadal primary site, and mediastinal lesions account for 60% of all germ cell tumors in adults. Germ cell tumors usually occur in young adults (mean age, 27 years). Most malignant germ cell tumors (>90%) occur in men, whereas benign lesions (mature teratomas) occur with equal incidence in men and women.

B FIG 38-52 Thymic squamous cell carcinoma. A, Contrast CT in the axial plane shows an anterior mediastinal mass (arrow) with focal calciication. There is stranding of the mediastinal fat anterior to the mass, suggesting invasion of the mediastinal fat. B, PET/CT in the axial plane depicts marked FDG uptake within the mass (arrow).

CHAPTER 38

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FIG 38-54 Mature teratoma. Contrast CT shows a large anterior mediFIG 38-53 Thymic carcinoid. Contrast CT shows a large anterior mediastinal mass. Note the heterogeneous appearance of the mass and iniltration of the mediastinum, with extension of the mass between vascular structures. A, aorta; S, superior vena cava.

astinal mass (arrowheads). The mass is heterogeneous in attenuation and is composed of fat, calcium, and luid. This CT appearance is typical of a mature teratoma. A, ascending aorta; D, descending aorta.

Mediastinal teratoma.48,49,61,95,133,192,200,222,223,248,257,291,297,321,325 Teratomas, the most common mediastinal germ cell tumors, are composed of elements that arise from more than one of the three primitive germ cell layers. Teratomas may broadly be classiied as benign or malignant. A histologic classiication system for extragonadal germ cell tumors by Gonzalez-Crussi categorizes teratomas as mature, immature-benign, immature-malignant, and malignant. Moran and Suster proposed a modiied classiication as mature, immature, and teratoma with additional malignant components. Regardless of the system, classiication is based upon tumor cellular composition. Mature or benign teratomas are composed of different tissue types (ectoderm, endoderm, mesoderm), with ectodermal derivatives predominating. The term dermoid cyst is commonly applied to tumors in which ectodermal components predominate. Mature teratomas are common, accounting for 70% of germ cell tumors in childhood and 60% of mediastinal germ cell tumors in adults. Mature teratomas occur most frequently in children and young adults. Patients may be asymptomatic, but chest pain, dyspnea, and cough due to compression of adjacent structures are common. By deinition, patients with mature teratoma have normal serum levels of β-human chorionic gonadotropin hormone (β-hCG) and α-fetoprotein (AFP); elevation of these markers implies a malignant component. Complete resection is the treatment for teratomas and results in complete cure. Despite a benign histology, these tumors may be dificult to remove because they are adherent to local structures. Whereas mature teratomas are benign, immature teratomas are potentially malignant and are composed of more than 10% embryonic immature elements at histopathologic evaluation, with varying degrees of differentiation. Immature-malignant teratomas are those that would otherwise be classiied histologically as benign but subsequently become metastatic after diagnosis. Malignant teratomas have immature histologic features but contain areas of malignancy (e.g., differentiated germ cell tumor, sarcoma, carcinoma), hence the nomenclature—immature teratoma with malignant components. These tumors are frequently metastatic at the time of diagnosis. Teratomas typically occur in the anterior mediastinum, although occurrence at other sites, including the middle mediastinum and posterior mediastinum, accounts for up to 20% of cases. Mature teratomas manifest on CT or MRI as smooth or lobulated mediastinal masses

A S

FIG 38-55 Mature teratoma. CT shows a large, predominantly waterattenuation anterior mediastinal mass with a small focal area of fat (arrow). Note the mass effect on the superior vena cava (S) and superior pulmonary vein (arrowheads). A, ascending aorta.

that typically have cystic and solid components; in contrast, malignant teratomas are usually poorly marginated masses containing areas of necrosis. The combination of luid, soft tissue, calcium, and fat is diagnostic of teratoma (Fig. 38- 54). The inding of a fat-luid level within a mass on CT or MRI is also diagnostic of teratoma. Fat occurs in up to 75% of mature teratomas and in up to 40% of malignant teratomas. However, only 17% to 39% of mature teratomas have all tissue components, and approximately 15% of mature teratomas manifest only a unilocular or multilocular cystic component (Fig. 38-55). Because of the varying composition of soft tissue, fat, calcium, and hemorrhage, MRI typically demonstrates heterogeneous signal intensity; this inding can be useful in differentiating teratomas from thymomas and lymphomas. Mature teratomas have been reported to rupture into the lung, pleural space, and pericardium in up to 33% of patients, and CT or MRI can be useful in detecting fat within these regions. The presence of nonhomogeneous internal components and other ancillary changes (e.g., adjacent parenchymal consolidation or atelectasis, pleural effusion, pericardial effusion) are signs of rupture

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PART II CT and MR Imaging of the Whole Body Nonseminomatous germ cell malignancies.167,191,200,228,237 Non-

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A

seminomatous germ cell tumors of the mediastinum include embryonal cell carcinoma, endodermal sinus tumor, choriocarcinoma, and mixed germ cell tumors, with the latter being the most common within this group. Most patients with malignant nonseminomatous germ cell tumors are symptomatic at presentation, with chest pain, cough, dyspnea, weight loss, and fever. Up to 80% of affected patients have elevated levels of AFP, and 54% have elevated levels of β-hCG. There is an association between malignant nonseminomatous germ cell tumors of the mediastinum and hematologic malignancies. Up to 20% of affected patients have Klinefelter’s syndrome. On CT or MRI these tumors manifest as large poorly marginated masses of heterogeneous attenuation or signal intensity (Fig. 38-59). Invasion of the adjacent mediastinal structures, chest wall, and lung, as well as metastases to the regional lymph nodes and distant sites, is common. FDG PET is useful in staging and for detection of recurrent or progressive disease, which usually appears as areas of increased uptake.

Parathyroid Adenoma8,41,82,141-143,151,160,171,187,188, 251,299,319,322

B FIG 38-56 Ruptured teratoma. A, Contrast-enhanced CT shows a heterogeneous anterior mediastinal mass (arrow). Note areas of enhancement and fat attenuation. There is stranding of the mediastinal fat (asterisk) and a small left-sided pleural effusion (arrowhead). B, Chest CT, lung window, demonstrates ground-glass opacities (arrow) surrounding the mass, suggesting rupture. (Case courtesy S.H. Paik, MD, Seoul, Republic of Korea.)

(Fig. 38-56). Malignant teratomas can be dificult to differentiate from benign mature teratoma at imaging unless invasion or metastatic disease is present (Fig. 38-57). FDG PET is of limited utility in evaluating mature teratoma (owing to the tumor’s lack of FDG avidity) but may be beneicial in identifying malignant immature components. Seminoma.10,183,200,228,230,310,325 Seminoma is the most common pure histologic type of malignant mediastinal germ cell tumor in men and accounts for 40% of such tumors. Affected patients are usually in the third or fourth decade of life and are symptomatic at presentation. Levels of β-hCG and AFP are normal; elevation of AFP indicates a nonseminomatous component of the tumor. On CT or MRI, seminomas manifest as large lobulated masses of homogeneous attenuation or signal intensity in the anterior mediastinum (Fig. 38-58). Cysts or areas of necrosis may also be seen in association with mediastinal seminoma. Invasion of adjacent structures is uncommon and calciication is rare. Metastases to regional nodes may occur. FDG PET is useful in staging and for detection of recurrent or progressive disease, usually seen as areas of increased uptake (see Fig. 38-58).

Because neck exploration for parathyroid gland removal is curative in more than 90% of patients with primary hyperparathyroidism, surgeons often do not obtain preoperative imaging studies to localize the parathyroid glands. However, 10% of parathyroid adenomas are ectopic in location, and the majority of ectopic adenomas are located either in the region of the tracheoesophageal groove or in the anterior mediastinum. Such ectopic adenomas can be missed at surgical exploration. Preoperative localization of ectopic parathyroid adenomas can reduce operative time, postoperative morbidity, and the need for repeat surgery. Imaging techniques for localizing abnormal parathyroid glands include sonography, radionuclide imaging (technetium 99m methoxyisobutylisonitrile [99mTc MIBI], 99mTc tetrofosmin), CT, and MRI. On CT, ectopic mediastinal parathyroid glands manifest as 1- to 2-cm rounded masses that may resemble lymph nodes (Fig. 38-60). CT or MRI can detect these glands, but careful evaluation is required so that small abnormalities are not overlooked. Whereas FDG does not accumulate in parathyroid adenomas, they are frequently avid for 11C methionine. MRI is accurate in identifying abnormal parathyroid glands in ectopic locations. Functioning parathyroid adenomas are intermediate in signal intensity on T1-weighted images and usually have markedly increased signal intensity on T2-weighted images (Fig. 38-61). Similar indings are seen in cases of parathyroid hyperplasia and carcinoma. However, up to 13% of abnormal glands do not have high signal intensity on T2-weighted images, owing to ibrosis or hemorrhage. Although MRI is comparable or superior to other imaging modalities for detecting parathyroid pathology (sensitivity, 78%; speciicity, 90%; accuracy, 90%), it is most appropriate as an adjunct to 99mTc MIBI radionuclide imaging. In this setting, MRI provides accurate anatomic localization of the adenoma and can be useful in predicting the need for mediastinotomy or a lateral cervical incision. Although the precise role of imaging in the evaluation of a virgin neck for hyperparathyroidism may be debated, imaging is useful in second-look procedures and in those patients considered to be at high risk for surgery. In this population, the success rate for surgery is lower, ranging from 64% to 90%, and the combined use of 99mTc MIBI and MRI has been shown to be 89% sensitive and 95% speciic for preoperative localization.

Lymphatic Malformations59,116,156,243,264,303,309,312,359 Lymphatic malformations are rare benign congenital lesions that account for 0.7% to 4.5% of all mediastinal masses. Approximately 75% occur in the neck, 20% in the axillary region, and 5% in the

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B FIG 38-57 Malignant teratoma. A, Contrast-enhanced CT shows a large heterogeneous mediastinal mass (M) with areas of luid (asterisk) and fat attenuation (arrow). The superior vena cava (S) is compressed and displaced. B, More inferiorly the mass contains marginal enhancing soft tissue (arrows) that invades and disseminates within the pericardium (arrowheads). Histopathology conirmed a high-grade immature teratoma with additional malignant components of embryonal carcinoma. S, superior vena cava.

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mediastinum. Primary mediastinal lymphatic malformations are rare, and most mediastinal lesions are due to extension from the neck. Lymphatic malformations are usually located in the superior mediastinum and anterior mediastinum, although they can occur in any mediastinal compartment. They usually occur in patients younger than 2 years, and there is a male predominance. In adults, lymphatic malformations are usually located in the mediastinum and are often due to recurrence of an incompletely resected childhood lesion that increases in size as lymphatic channels dilate with reaccumulated lymph. Lymphatic malformations are currently classiied as macrocystic or microcystic, replacing the corresponding outdated terms cystic hygroma and lymphangioma, respectively. On CT these lesions manifest as lobular multicystic tumors that surround and iniltrate adjacent mediastinal structures (Fig. 38-62). They can appear solid on CT because of protein or hemorrhage within the cysts. The cysts are typically 1 to 2 cm in diameter, and the septa may enhance following administration of IV contrast. MRI can be useful to conirm the cystic nature of these lesions; lymphatic malformations usually have markedly increased signal intensity on T2-weighted images. Their appearance on T1-weighted sequences is more variable, although most are generally of low to intermediate signal intensity (similar to skeletal muscle) and can contain focal areas of signal intensity greater than that of muscle. Occasionally, lymphatic malformations have high signal intensity similar to that of fat on T1-weighted images. Because surgical resection is the treatment of choice, multiplanar MRI can be useful in preoperative evaluation of local invasion and determination of the anatomic extent of tumor.

Hemangioma144,152,213,295,301,302

B FIG 38-58 Seminoma. A, CT shows an anterior mediastinal mass (M) with several small central areas of low attenuation, consistent with necrosis. B, PET/CT in the coronal plane demonstrates marked FDG activity. Note relationships to adjacent mediastinal structures.

Hemangiomas are rare mediastinal tumors that account for less than 0.5% of all mediastinal masses. Mediastinal hemangiomas usually occur in the anterior (68%) or posterior (22%) mediastinum, although multicompartment involvement is present in up to 14% of cases. Most mediastinal lesions are cavernous hemangiomas and are composed of large interconnecting vascular spaces with varying amounts of interposed stromal elements such as fat and ibrous tissue. Focal areas of organized thrombus can calcify as phleboliths. On radiographs, hemangiomas appear as sharp, smoothly marginated mediastinal masses. Phleboliths are seen in less than 10% of cases.

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FIG 38-59 Nonseminomatous germ cell malignancy (yolk sac tumor) that presented with superior vena cava syndrome. A, CT shows a large mixed-attenuation anterior mediastinal mass. There is tumoral invasion of the superior vena cava (arrow). B, PET/CT shows marked FDG activity, with several photopenic areas consistent with necrosis. Note FDG activity within the superior vena cava thrombus (asterisk).

A

B FIG 38-60 Ectopic parathyroid adenoma. A, Axial noncontrast CT shows a small soft tissue nodule (arrow) within the anterior mediastinum in a patient with persistently elevated serum calcium levels after undergoing neck dissection for hyperparathyroidism. This was thought to represent a small lymph node; however, the clinical history prompted further evaluation. B, 99mTc MIBI scan was positive (arrow), with pathology conirming an ectopic parathyroid adenoma.

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B FIG 38-61 Ectopic parathyroid adenoma in a woman with persistent hyperparathyroidism after surgical neck exploration. T1- (A) and T2-weighted (B) MRIs show a 1-cm mass (arrowheads) in the superior mediastinum, with intermediate signal intensity (similar to muscle) on the T1-weighted image and high signal intensity on the T2-weighted image. This appearance is typical of parathyroid adenoma. T, trachea; V, vertebral body. (From Erasmus JJ, et al: MR imaging of mediastinal masses. Magn Reson Imaging Clin N Am 8:59–89, 2000.)

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B FIG 38-62 Lymphatic malformation. A and B, Contrast CT shows a homogeneous water-attenuation mass (arrows) in the superior mediastinum that arises in the neck. The mass diffusely iniltrates the mediastinum and extends into the right hilum (B). S, superior vena cava; T, trachea.

CT typically reveals a heterogeneous mass with intense central and peripheral rimlike enhancement after administration of IV contrast (Fig. 38-63). Hemangiomas typically have heterogeneous signal intensity on T1-weighted images. In lesions with signiicant stromal fat, linear areas of increased signal intensity on T1-weighted images can occasionally be identiied. The central vascular lakes typically become markedly hyperintense on T2-weighted images, a potentially diagnostic feature (Fig. 38-64).

Middle Mediastinal Abnormalities Lesions that occur primarily in the middle mediastinum include esophageal lesions, airway lesions, foregut duplication cysts, and pericardial cysts.

Esophageal Lesions Esophageal cancer.60,96,119,134,162,184,185,190,195,234,263,269,279,282,334,341,349 CT is used to help stage esophageal carcinoma by demonstrating the length

of the lesion, thickness of the esophageal wall, involvement of adjacent structures (e.g., airway, aorta, pericardium, spine), and nodal spread to regional mediastinal, celiac, and gastrohepatic ligament nodes (Fig. 38-65). Endoscopy, endoscopic ultrasonography, and esophagography are also helpful in staging esophageal carcinoma. Invasion of local structures is common because the esophagus lacks a serosa. CT and MRI can over- or underestimate the degree of local invasion, because the lack of normal fat planes between the esophagus and adjacent structures makes invasion dificult to determine. Anterior displacement of the carina or left main bronchus suggests airway invasion; contact with the aorta that exceeds one quarter of the aortic circumference suggests aortic invasion. All imaging indings must be interpreted in conjunction with the patient’s clinical status when planning treatment. CT is also useful in planning radiation treatment ports and for imaging complications resulting from esophagectomy. Although esophageal malignancies can occasionally be detected by conventional chest CT after IV contrast (venous phase), acquisition of

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FIG 38-63 Hemangioma. A, Noncontrast CT shows a small homogeneous anterior mediastinal mass (arrowheads). A, ascending aorta. B, Contrast CT shows marked enhancement, typical of hemangioma (arrowheads). A, ascending aorta.

images during an earlier arterial phase can increase the sensitivity of detection.341 Esophageal cancer is usually FDG avid, with the exception of small and early T-stage tumors. Importantly, the detection of nodal and distant metastases by FDG PET increases the accuracy of staging and, by identifying unsuspected metastases, improves patient management (see Fig. 38-65). The role of FDG PET in evaluating the primary tumor’s response to neoadjuvant therapy in patients with esophageal cancer is currently being evaluated. Although initially promising results have been reported, the presence of therapy-induced inlammation and ulceration can lead to false-positive results in patients with a complete response to therapy. Additionally, because of the inability to detect residual microscopic disease, a negative PET scan does not preclude surgical resection. The normal esophagus is not optimally demonstrated on MRI because of peristaltic motion and relatively poor spatial resolution. Distinguishing small mucosal tumors from normal esophagus is dificult because both have intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The role of MRI for intrathoracic staging of esophageal neoplasms is limited, although some early reports on new techniques (e.g., surface coil and endoscopic MRI) have shown potential beneits. Some authors have reported high intrathoracic staging accuracy for MRI, but most reports suggest that MRI is no better than CT in this regard. More recently, combined PET/MR has been found to improve staging accuracy over MRI alone, with reported rates similar to endoscopic ultrasound, though the role of this modality remains to be validated. At present the primary utility of MRI in the evaluation of esophageal cancer is as a problem-solving modality, such as when invasion of the pericardium or heart is suspected on CT or when the patient is allergic to iodinated contrast material.

Esophageal dilatation.68,270 Esophageal dilatation can be easily demonstrated on CT. Focal dilatation occurs in Zenker’s diverticulum (upper esophagus), traction diverticula due to granulomatous disease (middle esophagus), and epiphrenic diverticula (lower right esophagus) (Fig. 38-66). These focal dilatations or diverticula are clearly demonstrated on CT and can be a source of confusion unless oral contrast material is administered. Diffuse dilatation of the esophagus can occur as a result of motility disorders (achalasia, postvagotomy syndrome, Chagas disease, scleroderma, systemic lupus erythematosus, presbyesophagus, diabetic neuropathy, esophagitis) or as a result of distal obstruction (carcinoma, stricture, extrinsic compression) (Fig. 38-67).

Airway Lesions11,28,47,163,176,206,207,214,216,256,260,285 Tumors of the trachea or proximal bronchi can manifest as middle mediastinal masses on chest radiographs or CT. Malignant neoplasms account for 90% of primary tracheal tumors. The most common primary malignancies of the trachea are squamous cell and adenoid cystic carcinoma. Benign neoplasms such as papilloma, adenoma, hamartoma, chondroma, leiomyoma, and granular cell myoblastoma account for less than 10% of primary tracheal tumors. The most common primary malignancy of the major bronchi is non–small cell lung cancer. Carcinoid tumors and mucoepidermoid carcinoma are less common bronchial malignancies that occur in younger patients. These lesions are discussed more fully in Chapter 37.

Foregut Cysts313,314 Foregut cysts, which account for approximately 20% of all mediastinal masses, most likely arise as a result of maldevelopment of the primitive foregut. Bronchogenic cysts are the most common mediastinal foregut cysts; esophageal duplication and neurenteric cysts are less common. It is important not to confuse these cystic masses with luid-illed

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C FIG 38-64 Hemangioma. A, Contrast CT shows a heterogeneous mass (arrowheads) in the anterior mediastinum. Note punctate calciication, consistent with a phlebolith within the mass (arrow). Asterisk, carotid artery; b, brachiocephalic artery; T, trachea. B, Coronal T1-weighted MRI shows a mass of intermediate signal intensity (arrowheads) in the anterior and superior mediastinum. Note septa within the mass and invasion of the mediastinum. H, heart; T, trachea. C, Axial T2-weighted MRI shows high signal intensity within the mass (arrowheads). This appearance is typical for hemangioma. Asterisk, carotid artery; b, brachiocephalic artery; T, trachea.

FIG 38-65 Esophageal malignancy. A, Noncontrast CT shows concentric thickening of the distal esophagus (arrow). B and C, Enlarged lymph nodes are depicted in the superior mediastinum (arrows). D and E, PET/ CT, coronal fusion, demonstrates avid uptake within the tumor and the mediastinal lymph nodes, consistent with metastases.

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structures within the mediastinum such as luid-illed pericardial recesses, loculated pleural luid, extension of ascites through the esophageal hiatus, mediastinal extension of pancreatic pseudocyst, or a luidilled and dilated esophagus (Figs. 38-68 and 38-69). Bronchogenic cyst.14,30,59,62,114,154,180,181,189,195,197,201,211,236,239,241,326 Bronchogenic cysts are thought to arise from abnormal budding of the

FIG 38-66 Epiphrenic diverticulum. CT after oral administration of barium demonstrates a lateral pouch (arrow) partially illed with contrast medium. The diverticulum was surgically removed.

ventral foregut. Histopathologically they are lined by ciliated respiratory epithelium, cartilage, smooth muscle, ibrous tissue, and mucous glands. Most bronchogenic cysts arise in the middle mediastinum, typically in the subcarinal or right paratracheal region, but may also occur in the anterior or posterior mediastinum. Bronchogenic cysts are found in unusual locations in up to 15% of cases, including the pleural space, diaphragm, pericardium, lung, or abdomen. Bronchogenic cysts may also rarely be pedunculated and can be mobile within the pleural space. On CT, bronchogenic cysts typically manifest as round or spherical, sharply marginated, homogeneous masses. Approximately half of bronchogenic cysts are of water attenuation on CT (Fig. 38-70). The remainder have increased attenuation, likely secondary to proteinaceous debris or hemorrhage within the lesions (Fig. 38-71). A small percentage have calciied walls or contain calcium suspended within the luid. MRI shows lesions that are typically of low to intermediate signal intensity on T1-weighted images and of markedly increased signal intensity on T2-weighted images. The lesions can be heterogeneous on T1-weighted images but are typically homogeneous on T2-weighted images. These MRI characteristics can be useful for differentiating cysts that appear solid on CT from solid neoplasms or lymphadenopathy. Gadolinium administration can also help distinguish mediastinal cysts from solid neoplasms by demonstrating lack of central enhancement and occasionally rim enhancement. Because many cardiac-gated T1-weighted pulse sequences have a relatively long TR, luid-illed lesions can be of intermediate signal intensity. Cysts with proteinaceous, mucinous, or hemorrhagic

B

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FIG 38-67 Achalasia. A, Barium swallow demonstrates marked dilatation of the esophagus. B and C, CT shows a dilated esophagus and abundant intraluminal debris. Note anterior displacement of the trachea.

CHAPTER 38 contents can have a further increase in signal intensity on these sequences (Fig. 38-72). However, these lesions usually have markedly increased signal intensity on T2-weighted images, suggesting their true cystic nature. Bronchogenic cysts do not exhibit FDG uptake on PET (see Fig. 38-71).

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attenuation due to intracystic hemorrhage or proteinaceous debris. On MRI they have signal intensity characteristics similar to those of bronchogenic cysts: variable signal intensity on T1-weighted images (depending on the intracystic contents) and markedly increased signal intensity on T2-weighted images (Fig. 38-74). Neurenteric cysts result from incomplete separation of the endoderm and notochord, resulting in a diverticulum of the endoderm. Neurenteric cysts, which are pathologically identical to esophageal duplication cysts, may have either a ibrous connection to the spine or an intraspinal component. These cysts are typically associated with vertebral body anomalies, most commonly a sagittal cleft, occurring at or above the level of the cyst. Most neurenteric cysts occur in the posterior rather than middle mediastinum, usually above the level of the carina. The CT and MRI appearance of these lesions is similar to that of other foregut cysts. MRI is optimal for demonstrating the extent of spinal abnormality and the degree of intraspinal involvement.

Esophageal duplication and neurenteric cysts.88,164,180,236,313,326 Duplication of the esophagus is thought to represent a diverticulum of the primitive foregut or an aberrant recanalization of the gut in embryogenesis. These cysts are located in the middle or posterior mediastinum and may be indistinguishable from bronchogenic cysts. They are composed of a muscular coat and mucosa that may resemble the esophagus, stomach, or small intestine, although it is usually ciliated. Esophageal duplication cysts usually occur within the wall of the esophagus or are adherent to it. They are either spherical or tubular and are usually located distally along the lateral aspect of the esophagus. On CT they typically manifest as spherical or tubular masses near the esophageal wall. They are usually homogeneous and of water attenuation (Fig. 38-73). Like bronchogenic cysts, they may be of soft tissue

Pericardial Cyst15,85,235,236,273,275,280,296,326 Pericardial cysts are unilocular mesothelium-lined cysts that arise from congenital defects related to the ventral and parietal pericardial recesses. True pericardial cysts contain all layers of the pericardium and do not communicate with the pericardial space. They are usually found in asymptomatic adults, often discovered incidentally on chest radiographs. They are typically unilocular cystic lesions with clear luid contents and thin walls. Pericardial cysts are variable in size and shape and most commonly occur in the right (70%) or left (22%) cardiophrenic angle. CT shows a homogeneous, nonenhancing, waterattenuation, rounded mass adjacent to the pericardium (Fig. 38-75). The cyst wall may calcify. Pericardial cysts are usually homogeneous on MRI, with low signal intensity on T1-weighted images and markedly increased signal intensity on T2-weighted sequences (Fig. 38-76).

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Posterior Mediastinal Lesions157 Neurogenic Tumors12,62,195,242,326,356 Neurogenic tumors account for 20% of all adult and 35% of all pediatric mediastinal neoplasms. Most neurogenic tumors occur within the posterior mediastinum, and neurogenic tumors account for the majority of posterior mediastinal neoplasms. These lesions can be classiied as tumors of the peripheral nerves (neuroibromas, schwannomas, malignant tumors of nerve sheath origin), sympathetic

FIG 38-68 Thoracic lymphocele after esophageal resection with posterior mediastinal gastric conduit. Contrast CT shows a large homogeneous luid collection (arrowhead) in the middle-posterior mediastinum, displacing the tracheal carina (asterisk) anteriorly and the gastric conduit anterolaterally. A, ascending aorta; D, descending aorta.

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B FIG 38-69 Mediastinal pseudocyst in a patient with chronic pancreatitis. A, Contrast CT shows a homogeneous water-attenuation mass (C) in the middle mediastinum, with a thin enhancing rim (arrowheads). Note small left pleural effusion. A, aorta; H, heart. B, More caudal CT image conirms the origination of the mass (arrowheads) from the tail of the pancreas. (Case courtesy May Lesar, Bethesda, MD.)

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B FIG 38-70 Bronchogenic cyst. A, Contrast-enhanced CT shows a well-circumscribed water-attenuation middle mediastinal mass (arrow) with an imperceptible wall. The mass is adjacent to the trachea (T) and aorta (A). B, CT coronal reformation depicts the relationship of the mass (arrow) with adjacent structures, such as the superior vena cava (arrowhead in A and B), aorta (A), and pulmonary arteries (P).

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B FIG 38-71 Bronchogenic cyst. A, Contrast-enhanced CT shows a large homogeneous mass (M) of soft tissue attenuation in the subcarinal region. B, PET/CT was performed, which shows no FDG uptake within the lesion (BC), a characteristic feature of bronchogenic cysts. BC, bronchogenic cyst.

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FIG 38-72 Bronchogenic cyst. Coronal T1-weighted MRI shows a subcarinal mass with high signal intensity due to viscous cyst luid. Note displacement of both main bronchi. A subcarinal location is typical for bronchogenic cysts. T, trachea.

FIG 38-74 Esophageal duplication cyst. Axial T1-weighted MRI shows a well-circumscribed mass (arrow) with high signal intensity adjacent to the descending aorta (A). This appearance, atypical for a simple cyst, is due to proteinaceous luid within the cyst.

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FIG 38-73 Esophageal duplication cyst. Noncontrast CT shows a wellmarginated low-attenuation middle mediastinal mass (arrow) adjacent to or possibly contiguous with the right lateral wall of the esophagus (asterisk). A, descending aorta.

ganglia (ganglioneuromas, ganglioneuroblastomas, neuroblastomas), or parasympathetic ganglia (paraganglioma, pheochromocytoma). Peripheral nerve tumors are more common in adults, and sympathetic ganglia tumors are more common in children. CT is usually performed in the initial evaluation of a suspected neurogenic tumor and is helpful in identifying intratumoral calciication and assessing associated bone erosion or destruction. Because neurogenic tumors usually arise in a paravertebral location, intraspinal extension is common. MRI is the preferred imaging modality for evaluating neurogenic tumors; it allows simultaneous assessment of intraspinal extension, spinal cord abnormalities, longitudinal extent of tumor, and extradural extension. Although the various types of neurogenic tumors can have similar radiologic appearances, there are certain features that aid in the differential diagnosis. Peripheral nerve tumors typically manifest in

FIG 38-75 Pericardial cyst. Contrast CT shows a large, homogeneous, water-attenuation mass (C) in the right cardiophrenic angle. Note the imperceptible wall; enhancement at the periphery (arrows) is due to an atelectatic lung. The location and appearance are typical of pericardial cysts.

adults as round masses oriented along the axis of a peripheral nerve, and there may be an intraspinal component (“dumbbell” lesion). Tumors of the sympathetic ganglia typically manifest in children as oval masses that are elongated along the spine and may contain calciications on CT. Benign peripheral nerve tumors.* Benign peripheral nerve tumors (schwannomas, neuroibromas) are slow-growing neoplasms and the most common neurogenic tumors of the mediastinum. Schwannomas are encapsulated neoplasms that arise from the nerve *References 9, 27, 40, 89, 97, 122, 174, 195, 199, 242, 278, 289, 326, 332, 356.

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PART II CT and MR Imaging of the Whole Body

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C FIG 38-76 Pericardial cyst. A, CT shows a small, low-attenuation, well-circumscribed mass in the right cardiophrenic angle (arrow). B and C, MRIs show that the mass is homogeneous, with low signal intensity on the T1-weighted image (B) and high signal intensity on the T2-weighted image (C). This MR appearance is typical of pericardial cysts.

sheath and typically have areas of cystic degeneration, hemorrhage, and small focal areas of calciication. Schwannomas grow lateral to the parent nerve and cause symptoms by compressing the nerve. Neuroibromas differ from schwannomas in that they are unencapsulated and result from proliferation of all nerve elements, including Schwann cells, nerve ibers, and ibroblasts. They grow by diffusely expanding the parent nerve. This type of neural tumor is found in neuroibromatosis (NF)1 (von Recklinghausen’s disease). Plexiform neuroibromas are variants that iniltrate along nerve trunks or plexuses. Schwannomas and neuroibromas typically occur with equal frequency in men and women, most commonly in the third and fourth decades of life. Between 30% and 45% of neuroibromas occur in patients with NF. Multiple neurogenic tumors or a single plexiform neuroibroma is pathognomonic of the disease. On CT, schwannomas and neuroibromas appear as sharply marginated, unilateral, spherical or lobular posterior mediastinal masses (Fig. 38-77). Pressure erosion of adjacent ribs or vertebral bodies or enlargement of the neural foramen occurs in up to 50% of cases. Punctate intralesional calciication occurs occasionally. On NCE CT, schwannomas are often of lower attenuation than skeletal muscle owing to their high lipid content, interstitial luid, and areas of cystic

degeneration. Neuroibromas are often more homogeneous and of higher attenuation than schwannomas because they have fewer of these histologic features. These lesions may heterogeneously enhance following administration of IV contrast. In several small series, schwannomas have been reported to be FDG avid on PET imaging. Neuroibromas can also be FDG avid. Recent studies have reported that malignant degeneration is usually associated with increased FDG uptake. On MRI, schwannomas and neuroibromas are of variable signal intensity on T1-weighted images but typically have similar signal intensity to the spinal cord. On T2-weighted images these neoplasms characteristically have high signal intensity peripherally and low signal intensity centrally (target sign) owing to collagen deposition. This feature, when present, helps distinguish neuroibromas from other mediastinal tumors. Also, areas of cystic degeneration within the lesions may result in foci of increased signal intensity on T2-weighted images. Although the high signal intensity of schwannomas and neuroibromas on T2-weighted images can facilitate differentiation of tumors from spinal cord, the tumors may be obscured by the high signal intensity of cerebrospinal luid. Schwannomas and neuroibromas, however, enhance with gadolinium, and this feature can be useful in detecting and determining the degree of intradural

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FIG 38-77 Schwannoma. A, Contrast-enhanced axial CT shows a large heterogeneous paraspinal mass (arrow). The rounded shape is typical of a peripheral nerve tumor. B, Coronal T1-weighted MRI shows that the mass (arrow) is homogeneous and isointense to skeletal muscle. C, Coronal T2-weighted MRI shows that the mass (arrow) is heterogeneously hyperintense, with internal septations. D, Coronal contrastenhanced T1-weighted MRI shows heterogeneous enhancement within the mass (arrow). Areas remaining hypointense represent focal degeneration.

extension of these tumors (Fig. 38-78). Ten percent of paravertebral neuroibromas and schwannomas extend into the spinal canal and appear as dumbbell-shaped masses, with widening of the affected neural foramen. CT of plexiform neuroibromas demonstrates low-attenuation iniltrative masses along the mediastinal nerves and sympathetic chains, which may occur in any mediastinal compartment (Fig. 38-79). MRI of plexiform neuroibromas also demonstrates the iniltrative nature of the tumors, and the masses have low signal intensity on both T1- and T2-weighted images owing to their ibrous nature.

Malignant tumor of nerve sheath origin.* Malignant tumors of nerve sheath origin (also termed malignant neuroibromas, malignant schwannomas, or neuroibrosarcomas) are rare neoplasms that typically develop from solitary or plexiform neuroibromas in the third to ifth decades of life. Up to 50% occur in patients with NF1; in such patients, these tumors occur at an earlier age (typically during adolescence) and with a higher incidence than among the general population. Because

*References 9, 27, 36, 72, 104, 135, 174, 199, 204, 242, 258, 326, 332.

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B FIG 38-78 Neuroibroma. A, Axial T1-weighted MRI shows a lobular mass (arrowheads) extending into the intervertebral foramina. V, vertebral body. B, Axial gadolinium-enhanced MRI shows homogeneous enhancement within the mass (arrowheads). V, vertebral body.

FIG 38-79 Plexiform neuroibromas in a woman with type I neuroibromatosis. Coronal noncontrast CT shows plexiform neuroibromas along the course of nerves within the posterior mediastinum (arrowheads).

most benign neurogenic tumors are asymptomatic, the development of pain often indicates malignant transformation. On CT or MRI, malignant tumors of nerve sheath origin typically manifest as posterior mediastinal masses larger than 5 cm in diameter. Although benign and malignant neurogenic tumors cannot be differentiated with certainty, indings that suggest malignancy include a sudden change in size of a preexisting mass or the development of heterogeneous signal intensity on MRI (caused by necrosis and

hemorrhage). The presence of multiple target signs throughout the lesion on MRI favors the diagnosis of a plexiform neuroibroma rather than a malignant tumor of nerve sheath origin. Neuroibrosarcomas are often FDG avid, and when the SUV is greater than 3, shorter mean survival time has been reported. Sympathetic ganglia tumors.4,19,46,63,97,242,293,308,320,326,332,344 Sympathetic ganglia tumors (ganglioneuromas, ganglioneuroblastomas, neuroblastomas) are rare neoplasms that originate from nerve cells. Ganglioneuromas and ganglioneuroblastomas usually arise from the sympathetic ganglia in the posterior mediastinum. Ganglioneuromas are benign neoplasms that usually occur in children and young adults. Ganglioneuroblastomas, which exhibit varying degrees of malignancy, usually occur in patients younger than 10 years. The posterior mediastinum is also the most common extraabdominal location of neuroblastomas, with up to 30% of these tumors occurring in this region. Neuroblastomas are highly malignant tumors that typically occur in children younger than 5 years. A posterior mediastinal mass in this age group should be considered a neuroblastoma until proved otherwise. Radiologically, ganglioneuromas and ganglioneuroblastomas usually manifest as well-marginated, elliptical, posterior mediastinal masses that extend vertically over three to ive vertebral bodies. They are usually located lateral to the spine and may cause pressure erosion on adjacent vertebral bodies. On CT they are typically heterogeneous and may contain stippled or punctate calciication (Fig. 38-80). On T1- and T2-weighted MRIs they are usually homogeneous and of intermediate signal intensity (Fig. 38-81). Occasionally these lesions are heterogeneous and of high signal intensity on T2-weighted images. Ganglioneuroblastomas are typically larger and more aggressive than ganglioneuromas, with evidence of local and intraspinal invasion. On CT, neuroblastomas manifest as paraspinal masses of heterogeneous predominantly soft tissue attenuation. The lesions usually contain areas of hemorrhage, necrosis, cystic generation, and calcium (30%). On MRI the lesions typically demonstrate heterogeneous signal intensity on all pulse sequences and show heterogeneous enhancement following gadolinium administration. Neuroblastomas often exhibit widespread local invasion and have irregular margins, although many of these lesions are well marginated on CT or MRI. Neuroblastomas also have a tendency to cross the midline.

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FIG 38-80 Ganglioneuroma. Contrast CT shows a well-circumscribed low-attenuation paraspinal mass containing punctate calciication (arrows). LA, left atrium.

FIG 38-82 Paraganglioma. Contrast CT shows a well-deined round mass occupying the aortopulmonary window (arrow). Note the marked enhancement.

(Fig. 38-83). Flow voids in the lesion are sometimes seen, indicating their hypervascular nature. The lesions may be well circumscribed or show invasion of surrounding mediastinal structures. The role of PET in paraganglioma imaging is not well established, owing to lack of speciicity and variable FDG uptake.

Lateral Thoracic Meningocele9,140,240,242,272,315

L S

FIG 38-81 Ganglioneuroma. Coronal T1-weighted MRI shows an elliptical paraspinal mass (arrowheads) of intermediate signal intensity. The vertical orientation and signal characteristics are typical of sympathetic ganglia tumors. L, liver; S, spleen.

Parasympathetic

ganglion

tumors.93,227,242,333 Paragangliomas

(chemodectomas) are rare neural tumors of the extraadrenal parasympathetic system. These tumors can be histologically identical to pheochromocytomas and can be functional or nonfunctional. Mediastinal paragangliomas occur in one of two locations: (1) in the middle mediastinum in close association with the origins of the aorta and pulmonary artery (aorticopulmonary paraganglioma) or (2) in the posterior mediastinum (paravertebral paraganglioma). On NCE CT the lesions are typically heterogeneous and enhance intensely after administration of IV contrast (Fig. 38- 82). On MRI the lesions are usually hypointense on T1-weighted images and hyperintense on T2-weighted images

Because of the pressure difference between the thorax and subarachnoid space, pulsion diverticula called lateral meningoceles can develop and protrude through the adjacent neural foramina. They occur most commonly in patients with NF1. Lateral meningoceles manifest radiographically as well-circumscribed paravertebral masses that usually occur on the convex side of a scoliosis. On CT, meningoceles appear as well-circumscribed paraspinal masses of water attenuation. The adjacent neural foramen is typically enlarged. These lesions can be confused with low-attenuation neuroibromas. The diagnosis is established by demonstrating communication with the subarachnoid space by CT myelography. MRI can also be helpful in differentiating meningoceles from neuroibromas, because meningoceles typically have low signal intensity on T1-weighted images and high signal intensity on T2-weighted images and do not enhance after gadolinium administration. Cardiac-gated MR cine images of meningoceles can reveal pulsatile motion owing to communication with the subarachnoid space.

Extramedullary Hematopoiesis33,107,118,156,223,242,300 Extramedullary hematopoiesis is a compensatory phenomenon that occurs when erythrocyte production is diminished or destruction is accelerated. Extramedullary hematopoiesis is usually seen in patients with chronic hemolytic disorders such as thalassemia, hereditary

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A

A

D

B

A

FIG 38-83 Paraganglioma. A, CT shows a homogeneous soft tissue mass in the aortopulmonary window (arrowheads). Note that the mass is dificult to distinguish from the aorta. A, ascending aorta; D, descending aorta. B, Coronal T1-weighted MRI shows an aortopulmonary window mass (arrowheads) of intermediate signal intensity. Biopsy revealed paraganglioma. A, aorta; T, trachea.

spherocytosis, sickle cell disease, or extensive bone marrow replacement secondary to myeloibrosis. Extramedullary hematopoiesis is usually microscopic and commonly involves the liver, spleen, and lymph nodes. Thoracic manifestations are less common and consist of paravertebral soft tissue masses. The masses represent extrusion of the marrow through the thinned cortex of the posterior ribs. Histologically the masses resemble splenic tissue, with hematopoietic elements mixed with fat. The masses are usually bilateral, contain no calciication, and cause no rib destruction. Additional masses can be found along the lateral margins of the ribs. On CT, extramedullary hematopoiesis manifests as a heterogeneous mass or masses, often with focal areas of fat within the lesion (Fig. 38-84). The typical MRI appearance consists of well-marginated, smooth or lobulated, unilateral or bilateral paravertebral masses. T1- and T2-weighted MRIs typically show bilateral heterogeneous masses with increased signal intensity on T1-weighted images because of fat within the masses.

Paraspinal Inlammation5,6,58,220,255 Vertebral osteomyelitis can result in a paraspinal abscess. Causative organisms include Mycobacterium tuberculosis, Staphylococcus aureus, and anaerobic organisms. On CT a paraspinal abscess appears as a mass of heterogeneous attenuation. Rim enhancement following administration of IV contrast is characteristic. Imaging features that suggest paraspinal abscess include narrowing of the adjacent intervertebral disk and destruction of two or more contiguous vertebral bodies. Spondylitis and vertebral osteomyelitis are often accompanied by epidural or paraspinal inlammatory masses or abscesses (Fig. 38-85). MRI is especially well suited for identifying and demonstrating the extent of paraspinal infections because of its ability to depict the disk space, the spinal canal and its contents, and the paraspinal regions. T1-weighted images show inlammation as low signal intensity, and T2-weighted images show it as high signal intensity. The addition of gadolinium is helpful in demonstrating the extent of disease.

Diffuse Mediastinal Abnormalities Numerous lesions can manifest as diffuse or multicompartmental mediastinal disease, including lymphadenopathy, mediastinitis, lymphoproliferative disorders, and metastatic disease.

Lymphadenopathy21,31,69,98,101,111,132,195,259,265,342,346 Lymph nodes are common in all regions of the mediastinum but are most numerous around the tracheobronchial tree in the middle mediastinum (Fig. 38-86). Though still a subject of some controversy, the generally accepted upper limit of normal for short-axis lymph node diameter is 1 cm. Although enlargement is the primary CT or MR criterion for establishing the presence of lymph node disease, attenuation is also important. For instance, diffuse calciication is typical of prior granulomatous infection (e.g., tuberculosis, histoplasmosis), sarcoidosis, silicosis, calcifying or ossifying metastases, and treated lymphoma (Fig. 38-87). Nodes with low-attenuation centers and rim enhancement are often seen in patients with active infection (e.g., tuberculosis, nontuberculous mycobacterial disease) and in patients with metastatic disease to the lymph nodes (e.g., lung cancer, testicular germ cell malignancy). Diffuse intense nodal enhancement after administration of IV contrast material is typical of Castleman’s disease and some metastatic processes (e.g., renal cell carcinoma). Causes of mediastinal lymph node enlargement may be classiied as follows: • Primary neoplasms of lymph nodes (e.g., lymphoma, leukemia) • Metastases from intrathoracic or extrathoracic primary malignancies • Nonlymphomatous lymphoid disorders such as Castleman’s disease • Infection (e.g., tuberculosis, fungal infection) CT and MRI are generally considered to be equivalent in their ability to detect mediastinal lymph node enlargement (Fig. 38-88). MRI is limited in its ability to detect calciication within nodes, a inding useful for distinguishing benign from malignant lymphadenopathy. Furthermore there is considerable overlap in signal intensity characteristics of benign and malignant lymphadenopathy on both T1- and T2-weighted images; thus CT remains the primary modality for diagnosis and characterization of the morphologic features of mediastinal lymphadenopathy. Whereas CT is limited to morphologic information, FDG PET provides quantitative physiologic information as a surrogate marker for malignancy. The role of FDG PET and coregistered PET/CT are well

CHAPTER 38

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A A

A B

A

C FIG 38-84 Extramedullary hematopoiesis. A, Axial noncontrast CT shows well-circumscribed bilateral paravertebral soft tissue masses (arrowheads). B, A more superior level demonstrates a soft tissue mass (arrowhead) with medullary expansion of the bilateral posterior ribs (arrows), a common associated inding. C, Contrast-enhanced CT in a different patient also demonstrates bilateral paravertebral soft tissue masses (arrowheads) containing macroscopic areas of fat, typical for extramedullary hematopoiesis. A, descending aorta.

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*

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*

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FIG 38-85 Paraspinal abscess with spondylodiskitis due to Mycobacterium tuberculosis. A, Axial contrastenhanced CT shows bilateral enhancing paraspinal masses (arrows) with associated vertebral body destruction. M. tuberculosis was cultured from needle aspirate. B, CT coronal reconstruction better depicts vertebral body collapse and destruction with adjacent paraspinal collections (asterisk). C, Axial T1-weighted postcontrast MRI deines the extent of paravertebral inlammatory changes. D, Sagittal T2-weighted MRI shows associated cord compression (arrow) resulting from spondylodiskitis. A, descending aorta.

CHAPTER 38

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D FIG 38-86 Diffuse mediastinal adenopathy in a patient with chronic lymphocytic leukemia. Contrast CT shows marked intrathoracic adenopathy in the paratracheal and prevascular mediastinum (A), precarinal region and aortopulmonary window (B), left and right hilum (C), and subcarinal region (D). Note the axillary adenopathy (arrowheads in A). A, ascending aorta; B, brachiocephalic vein; D, descending aorta; P, main pulmonary artery; S, superior vena cava; T, trachea; TA, transverse aorta.

A

P

P

FIG 38-87 Osteosarcoma metastasis to the anterior mediastinum. Contrast CT shows a soft tissue–attenuation mass with extensive osteoid (arrowheads) in the anterior mediastinum. A, aorta; P, pulmonary artery.

established in mediastinal lymph node staging; however, false positives can be seen in the setting of inlammatory and infectious diseases, and false negatives can occur in relation to technique and with certain malignancies. Like PET/CT, recent advances in MRI technology have greatly improved the imaging properties of mediastinal lymph nodes

beyond size assessment. Several studies indicate that MR sequences (e.g., short tau inversion recovery [STIR] turbo-spin echo, DWI) can differentiate benign from malignant nodes with similar or improved accuracy as compared to FDG PET. Although these small series are promising, the utility of DWI for lymph node characterization has yet to be validated in large randomized controlled trials. Lymphoma.80,90,123,158,179,194,200,237,304,324 Lymphomas are common mediastinal neoplasms that can be either focal or diffuse. Lymphomas are classiied as either Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL). HD is the most common mediastinal lymphoma. Of the four types of HD, nodular sclerosing is the most common type and has a unique predilection for the anterior mediastinum. Other types of HD typically manifest with diffuse mediastinal lymphadenopathy. NHL that involves the mediastinum usually manifests with diffuse lymphadenopathy involving anterior, middle, and occasionally posterior mediastinal nodal groups. However, large B-cell or lymphoblastic lymphoma can manifest as an isolated anterior mediastinal mass. These large tumors can obstruct the SVC, compress the airway, or invade the chest wall or adjacent structures. Hodgkin’s disease. HD accounts for 0.75% of all cancers diagnosed in the United States each year. The median age at diagnosis is 26 years, and there is a slight male predominance. The incidence of HD has a bimodal distribution with peaks between 25 and 30 years and 75 and 80 years. The characteristic Reed-Sternberg cell is the diagnostic hallmark of HD. There are four histologic subtypes of HD:

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S A T T

B

A

A S

C FIG 38-88 Metastatic mediastinal adenopathy in a patient with melanoma. A to C, Axial T1-weighted images of the chest show lymph nodes of intermediate signal intensity in the high paratracheal (A), low paratracheal (B), and precarinal and aortopulmonary window (C) regions (white arrows). Note the small prevascular lymph node (black arrow in B). A, aorta; S, superior vena cava; T, trachea.

• •

Lymphocyte predominance (5% of cases): the best prognosis Nodular sclerosing, the most common type (78%): the second most favorable prognosis • Mixed cellularity (17%): the third most favorable prognosis • Lymphocyte depletion (1%): the worst prognosis HD is staged using the Ann Arbor staging system (Table 38-2). The absence or presence of fever or night sweats or the unexplained loss of 10% or more body weight 6 months before diagnosis is denoted by the sufix A (designating absence of these symptoms) or B (designating presence of these symptoms). Stages I and II are treated with radiation alone, and stages III and IV are treated with a combination of radiation and chemotherapy or with chemotherapy alone. Survival is greater than 90% in stages I, II, and IIIA; 80% in stage IIIB; and 75% in stage IV. Non-Hodgkin’s lymphoma. The NHLs are a heterogeneous group of diseases with different histologies, treatments, and prognoses but with enough similarities that they are considered collectively. Although there is no known cause of NHL, patients with impaired immune systems have a higher risk of developing this malignancy. NHL accounts for up to 3% of all newly diagnosed cancers in the United States and is four times more common than HD. NHL is the third most common childhood cancer, although the median age at

Ann Arbor Classiication Staging System for Hodgkin’s Disease TABLE 38-2 Stage

Description

I II

Involvement of a single lymph node region Involvement of two or more lymph node regions on same side of diaphragm Localized involvement of an extralymphatic organ or site and one or more lymph node regions on same side of diaphragm Involvement of lymph node regions on both sides of diaphragm Involvement of lymph node regions on both sides of diaphragm accompanied by involvement of spleen Involvement of lymph node regions on both sides of diaphragm accompanied by localized involvement of an extralymphatic organ or site Involvement of lymph node regions on both sides of diaphragm accompanied by both involvement of spleen and localized involvement of an extralymphatic organ or site Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement

IIE III IIIS IIIE

IIIES

IV

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Histologic Classiication of Non-Hodgkin’s Lymphoma TABLE 38-3 Grade

Description

Low

Small lymphocytic Follicular with predominantly small cleaved cell Follicular with mixed small and large cell Follicular with predominantly large cell Diffuse with small cleaved cell Diffuse with mixed small and large cell Diffuse with large cleaved cell Noncleaved Diffuse large cell and immunoblastic Small noncleaved cell and lymphoblastic

Intermediate

High

the time of diagnosis is 55 years. There is a male predominance (1.4 : 1). The histologic classiication of NHL is complex, with 10 different cell descriptions divided into three different grades of tumor (Table 38-3). The two most common types of mediastinal NHL are diffuse large B-cell lymphoma and T-cell lymphoblastic lymphoma. Treatment is complex and involves radiation for the lower-grade tumors and chemotherapy for the higher-grade tumors. Survival is 50% to 70% for low-grade NHL, 35% to 45% for intermediate-grade NHL, and 20% to 30% for high-grade NHL. Several unique observations are seen in NHL: low-grade tumors may spontaneously regress, recur, or transform into higher grade tumors. The incidence of NHL is higher in patients with severe immune compromise, including congenital immune disorders, transplant immunosuppression, and HIV. NHL in these patients is often more aggressive and involves extranodal sites such as the central nervous system, lung parenchyma, and gastrointestinal tract. Imaging of lymphoma.* CT is the most readily available and historically used modality for identifying and staging HD and NHL. CT provides accurate measurement of initial tumor size and extent, as well as a means of following the response to therapy (Figs. 38-89 to 38-96). Chest CT alters the initial treatment plan in approximately 10% of patients with HD by detecting more extensive disease. The anterior mediastinal, pretracheal, and hilar nodes are most commonly involved with HD. Paracardiac, subcarinal, superior diaphragmatic, internal mammary, and axillary nodes are less frequently involved. Calciication within nodes is usually a consequence of radiation therapy but is occasionally detected before treatment. Central areas of low density represent areas of necrosis, which does not appear to alter the treatment response or survival. Lymphadenopathy varies in size and extent and can manifest as a solitary large mass or discrete nodes within masses of matted nodes. Bulky mediastinal lymphadenopathy, deined as the diameter of the nodal mass exceeding one third of the thoracic diameter, is an important distinction because it may alter prognosis and therapy. When presenting as a dominant anterior mediastinal mass, features of HD include irregular contours, surface lobulation, and absence of vascular involvement. In comparison, NHL typically has regular contours.

*References 2, 7, 13, 24, 37, 42, 45, 57, 99, 100, 149, 195, 209, 238, 247, 252, 271, 317, 338, 339, 360.

A

A

A

* *

B FIG 38-89 Hodgkin’s lymphoma in a young woman. A, CT shows a homogeneous anterior mediastinal mass (arrows). The arrowhead points to the superior vena cava. A, ascending aorta. B, PET/CT in the coronal plane. The mass shows marked FDG activity (arrows). Note the associated left neck mass (arrowhead). The left ventricle activity (asterisk) is normal. A, ascending aorta.

Intrathoracic disease is noted in only 40% to 50% of patients with NHL at presentation, compared with 85% of those with HD. Whereas the most common nodal sites of involvement in HD are the anterior and superior mediastinal nodes, NHL typically involves other nodal sites, lung parenchyma, pleura, and pericardium. HD has a propensity to spread via contiguous nodal groups compared to NHL, which has multifocal nodal involvement. FDG PET has become the primary imaging modality in the staging and management of patients with lymphoma, replacing gallium-67 scintigraphy. PET/CT has been shown to have better accuracy in demonstrating nodal involvement as well as extranodal sites, thereby improving accuracy of initial staging compared to CT alone. Metabolic activity on initial PET has been shown to be predictive of tumor grade and prognosis, with higher uptake being a sign of more aggressive lymphoma. In addition, FDG PET has high diagnostic accuracy in the early prediction of response to chemotherapy, is useful for restaging lymphoma after initial treatment, and aids in the detection of early

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S A

* A FIG 38-90 Hodgkin’s lymphoma. Contrast CT shows a large anterior mediastinal mass with a large cystic component. Note posterior displacement of the right main bronchus (asterisk). A, ascending aorta. A

S

relapse after completion of therapy. Of particular interest is the ability of FDG PET to detect persistent posttherapy lymphoma within residual masses discovered on conventional imaging studies that may warrant further treatment (Fig. 38-97). PET has also been used to help distinguish normal thymus and thymic rebound from primary or recurrent mediastinal lymphoma. Despite its utility, one primary limitation of PET/CT is that certain subtypes of lymphoma, such as extranodal marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue (MALT), are frequently not FDG avid. Although MRI can reveal additional information in as many as 15% of cases, it is more often used to assess suspected SVC obstruction, vascular invasion, and chest wall or mediastinal invasion. MRI has also been used to monitor and evaluate response to therapy, differentiate ibrosis from residual tumor, and detect recurrent lymphoma. Residual masses are seen in the immediate follow-up period in up to 88% of patients with HD and 40% of patients with NHL. These residual masses typically resolve over 12 to 18 months. The presence of residual mediastinal abnormalities is of concern because lymphoma eventually recurs in half of these patients, usually at the site of the original mass. Distinction of a residual ibrotic mass from persistent or recurrent tumor can be dificult by conventional imaging. MRI and PET/CT can be useful for this assessment. Because of its high water content, untreated lymphoma is typically homogeneous with low to intermediate signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. Patients with nodular sclerosing HD occasionally have focal regions of low signal intensity within the mass on pretreatment T2-weighted images because of intralesional ibrosis. During and immediately after completion of therapy, the lesions typically become heterogeneous on MRI, and signal intensity on T2-weighted images becomes more variable. Over the subsequent 4 to 6 months, there is a tendency for the residual mass to decrease in size and signal intensity on T2-weighted images. Six months after therapy, residual masses due to ibrosis should be homogeneous, with low signal intensity on both T1- and T2-weighted images. This homogeneous low signal intensity is typical of treated inactive lymphoma. If the mass remains heterogeneous with focal regions of high signal intensity on T2-weighted images, recurrent or residual lymphoma is suggested. Based on these indings, MRI can detect persistent or recurrent tumor in treated patients as early as 8 to 12 weeks before the onset of clinical symptoms. The presence of fat

B

A S

C FIG 38-91 Nodular sclerosing Hodgkin’s lymphoma. A, T1-weighted MRI shows a lobular heterogeneous anterior mediastinal mass with intermediate signal intensity. A, aorta; S, superior vena cava. B and C, T2-weighted MRIs show that the mass has heterogeneous signal intensity. On the cephalic image (B) there are areas of decreased signal intensity, consistent with intratumoral ibrosis. On the caudal image (C) the mass is of predominantly high signal intensity, similar to subcutaneous fat. A, aorta; S, superior vena cava. (From Erasmus JJ, et al: MR imaging of mediastinal masses. Magn Reson Imaging Clin N Am 8:59–89, 2000.)

mixed with residual ibrotic tissue, however, represents a pitfall of MRI. This potential misinterpretation can be avoided by realizing that regions of high signal intensity on T2-weighted images correlate with high-signal-intensity fat on T1-weighted images (rather than the low signal intensity of recurrent tumor). Fat-suppression pulse sequences may also be helpful for distinguishing interspersed fat from areas of residual tumor.

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Castleman’s disease.32,44,67,79,127,155,159,170,186,212,215,224,253,262,277,316 Cas-

A

P

tleman’s disease is a benign lymphoproliferative disorder also known as angiofollicular hyperplasia or giant lymph node hyperplasia. Based on pathologic characteristics, the disease is currently classiied into three major subgroups: hyaline vascular variant (HVV), plasma cell variant (PCV), and plasmablastic multicentric Castleman’s disease. PCV is further subclassiied as unicentric or multicentric. Approximately 70% of cases occur in the chest, 15% in the abdomen and pelvis, and 15% in the neck.

Unicentric hyaline vascular variant and unicentric plasma cell variant. Unicentric HVV is the most common form of CastleA

T

B

L

H

C FIG 38-92 Non-Hodgkin’s lymphoma manifesting as a mediastinal mass with chest wall involvement. A to C, Contrast CT shows a diffuse anterior mediastinal mass with chest wall invasion. Note enlarged axillary nodes (arrowheads in A). The mass extends into the neck and surrounds vessels (arrow in B). More caudally the mass manifests as a mantle of soft tissue encasing the heart (C). A, ascending aorta; H, heart; L, liver; P, main pulmonary artery; T, trachea.

man’s disease and accounts for approximately 70% of all cases. Although all age groups are affected, there is a peak incidence in the fourth decade of life. There is no gender predilection, and patients are usually asymptomatic. Unicentric HVV typically manifests as enlargement of either a single lymph node or a single chain of lymph nodes in the neck, mediastinum, abdomen, and axilla. Diagnosis usually requires excisional lymph node biopsy rather than ine-needle aspiration. Unicentric PCV accounts for about 20% of all cases and usually affects a single chain of lymph nodes rather than a solitary node. The peak incidence is in the third decade of life; like HVV, there is no gender predilection. The most common location is the abdomen. Clinically, unicentric PCV presents with constitutional symptoms, anemia, and elevated sedimentation rates. Excisional lymph node biopsy is usually required to conirm the diagnosis. A mixed form of Castleman’s has also been described when HVV and PCV disease occur in the same patient. Imaging studies show one of three major morphologic patterns: solitary mass (50%), dominant iniltrative mass with associated lymphadenopathy (40%), or diffuse lymphadenopathy conined to a single mediastinal compartment (10%). Identiication of the irst pattern suggests that complete surgical resection is likely. Identiication of the second or third pattern suggests that complete excision may be dificult or impossible. On NCE CT, localized HVV Castleman’s disease manifests as a homogeneous or heterogeneous mass of soft tissue attenuation. Calciication is uncommon (5%-10%) and is typically coarse and central in location. HVV typically enhances intensely following the IV administration of iodinated contrast (Fig. 38-98). Prominent feeding vessels may also be shown on contrast-enhanced CT. Rarely Castleman’s disease can present as a well-deined pleural or pericardial mass or pleural effusion. On MRI, Castleman’s lesions are typically heterogeneous and of increased signal intensity (compared with skeletal muscle) on T1-weighted sequences; they become markedly hyperintense on T2-weighted sequences. Low-signal-intensity septa are occasionally visible. In larger lesions, low voids in and around the mass may be identiied and are important clues to the hypervascular nature of the lesions. Because of this hypervascularity, diffuse enhancement following administration of IV gadolinium is common (Fig. 38-99).

Multicentric plasma cell variant and plasmablastic multicentric Castleman’s disease. The multicentric PCV of Castleman’s DWI is emerging as a potential alternative to PET/CT for the initial staging of lymphoma. Lymphomatous nodes show restricted diffusion on DWI, with corresponding low ADC values. This applies to both the more common lymphoma subtypes and the less common subtypes that are typically not FDG avid and therefore dificult to stage with PET/CT. Early studies show good agreement between MR DWI and PET/CT, suggesting that MRI may prove to be a particularly good alternative in children and patients requiring long-term follow-up for lymphoma in order to minimize radiation dose.

disease exists in two forms, depending on whether the patient has been infected with human herpesvirus type 8 (HHV-8). Multicentric Castleman’s disease with prior HHV-8 infection is classically referred to as multicentric PCV. Multicentric PCV accounts for 10% of all cases, and the disease typically affects multiple nodes or chains of nodes. There is no gender predilection, the median age at presentation is in the fourth to sixth decades, and patients usually have systemic symptoms such as fever, weight loss, and night sweats. HHV-8-positive multicentric Castleman’s disease occurs in both HIV-positive and HIV-negative patients. HIV-positive patients are almost always HHV-8 positive;

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C FIG 38-93 Non-Hodgkin’s lymphoma manifesting as multifocal disease. A, Noncontrast CT shows a large iniltrative anterior mediastinal mass (arrows). A, aorta; P, left pulmonary artery. B, PET/CT in the axial plane. The mass shows intense FDG activity. A more photopenic area in the center represents necrosis. C, PET/ CT in the coronal plane. Arrows identify the anterior mediastinal mass. Additional foci of disease are identiied in the neck and abdomen (arrowheads).

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Castleman’s disease is usually moderately FDG avid on PET but less than that typically seen with mediastinal malignancy (e.g., lymphoma, thymoma, metastatic nodes). SUV values tend to be higher in multicentric disease compared to unicentric disease. Detection of additional foci of disease is helpful for staging, evaluation of treatment, and recognition of recurrence.

Mediastinitis26,52,91,136,281,290 Acute mediastinitis.29,35,113,153,161,175,221,283,337,352 Acute bacterial medi-

A

A

B FIG 38-94 Non-Hodgkin’s lymphoma manifesting as multifocal disease. A, CT shows a right paravertebral soft tissue mass (arrowhead). Axillary adenopathy can be seen (arrows). B, CT at a more caudal level shows bilateral paravertebral masses (arrowheads). Small pleural effusions can be visualized bilaterally. A, aorta.

clinically the disease has a higher prevalence of pulmonary symptoms and a stronger association with Kaposi’s sarcoma. Among multicentric PCV patients who are HIV negative, the prevalence of HHV-8 infection is approximately 40%. Multicentric PCV is also associated with POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. A new variant of multicentric Castleman’s disease has been described in Japan and is referred to as Castleman-Kojima disease or TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin ibrosis, organomegaly). This variant is also characterized by ascites, microcytic anemia, myeloibrosis, and renal dysfunction. Lymph nodes in these patients are typically smaller ( 0.5 Pleural luid LDH–to–serum LDH ratio > 0.6 Pleural luid LDH > 2/3 times the upper limit of normal for serum

Radiography

various modalities in the diagnosis and treatment of pleural effusion are summarized in Table 39-2. Radiography and ultrasound. Typical radiographic indings include unilateral or bilateral blunting of the costophrenic or cardiophrenic sulci with a meniscus sign, diaphragmatic silhouetting, luid in the issures, and mediastinal shift in cases of large effusion. Detection of pleural luid on radiographs requires at least 175 mL on upright frontal radiographs, 75 mL on lateral views (in the posterior costophrenic sulcus), and as little as 10 mL on lateral decubitus views, which are most sensitive.123 Identiication of hydropneumothorax or empyema (loculated effusion) is often possible with radiography (Fig. 39-8). Whether the effusion is unilateral (more likely exudative) or bilateral (more likely transudative) may be helpful in determining the character of an effusion in a given clinical context, though there is considerable overlap; biochemical analysis of pleural luid is usually necessary for deinitive assessment. After thoracentesis, radiography is routinely used to evaluate for complications such as pneumothorax. After evacuation of large pleural effusions, postthoracentesis pneumothorax ex vacuo, or “trapped lung,” may occur and should not be confused with iatrogenic pneumothorax caused by pulmonary puncture.11 The appearance of pneumothorax ex vacuo is caused by air in the pleural space, with lack of reexpansion of the chronically atelectatic or ibrotic lung (Fig. 39-9). Ultrasound is more accurate than radiography for estimating pleural luid volume (as little as 5 mL may be detected) and more sensitive than CT in identifying septations.51,61 Importantly, ultrasound is useful in guiding interventions such as diagnostic and therapeutic thoracentesis, particularly in cases of small or loculated effusion, and pleural mass biopsy.34,77 Sonography has also been used to guide chest tube drainage and thoracoscopy in patients with parapneumonic effusion and empyema.15 CT. CT is more sensitive than radiography for detection of small pleural effusions.34 The capability of CT to evaluate the entire pleural surface, lung parenchyma, mediastinum, and chest wall makes it the ideal modality for gauging the extent and nature of pleural luid collections.51 Small simple effusions are seen as meniscoid low-attenuation collections that layer dependently, whereas loculated effusion is most often seen as lenticular luid-attenuation masses along the dependent

Role of Imaging Modalities in Cases of Pleural Effusion

Ultrasound

CT

MRI

• First-line modality for detecting effusion • Often useful in detecting loculated effusion or hydropneumothorax • Whether effusion is unilateral or bilateral may suggest transudate or exudate and guide differential diagnosis, though biochemical analysis is usually necessary for deinitive assessment. • Used to assess for complications after thoracentesis • Can detect smaller amounts of luid than radiography • Whether effusion is anechoic or complex may suggest transudate or exudate and guide differential diagnosis, though biochemical analysis is usually necessary for deinitive assessment. • More sensitive than CT for identifying septations • Often used to guide procedures • Portability an asset in assessment of critically ill patients • Comprehensive assessment of the entire pleura and adjacent structures in three dimensions • Higher contrast resolution than both radiography and ultrasound helpful for characterizing pleural luid content by attenuation and enhancement characteristics • Useful for guiding intervention in selected cases not amenable to ultrasound • Limited role in evaluation of nonmalignant pleural effusions • May be useful in cases of suspected tumoral rib or chest wall invasion because of superior contrast resolution • DWI may help discriminate exudate (higher intensity on DWI, lower ADC) from transudate, but this may not be practical in routine clinical contexts.

posterior pleural surface.51 CT readily diagnoses loculated effusion in the major or minor issure, which produces a pseudotumor appearance on plain radiographs. At times it may be dificult to differentiate pleural effusion from ascites using CT in a supine patient. Table 39-3 lists some signs that may be helpful in making this distinction. Attenuation values (Hounsield units [HU]) are sometimes helpful in determining the content of a pleural effusion. Acute hemothorax is seen as a high-attenuation effusion. Whether attenuation value is

CHAPTER 39

Disease of the Pleura, Chest Wall, and Diaphragm

A

B

C

D FIG 39-8 A, Axial CT image showing a right-sided transudative effusion in a patient with chronic renal failure. B, Loculated small right pleural effusion with the “split pleura sign” in a patient with empyema. C, Fissural pleural thickening in a patient with right pleural mesothelioma. D, Large left hemothorax after resection of a left-sided bronchogenic cyst.

A

B FIG 39-9 Chest PA views before (A) and after (B) right-sided thoracentesis, showing lucency in the right lower hemithorax (pneumothorax ex vacuo, or “trapped lung”).

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Signs Useful for Distinguishing Pleural Effusion from Ascites on Supine CT TABLE 39-3

“Displaced crus” sign32

“Interface” sign116

“Diaphragm” sign2 Sparing of the “bare area” of the liver90

Anterior displacement of the diaphragmatic crus by pleural luid adjacent to the vertebral bodies, not seen in ascites Hazy rather than sharp interface between pleural luid and the abdominal viscera created by diaphragmatic interposition; ascites has a sharp interface with the liver or spleen owing to lack of diaphragmatic interposition. Pleural luid lies peripheral to the diaphragm rather than ascites, which lies medially. Ascites cannot interpose between the posterior right lobe of the liver and the abdominal wall because this portion is attached directly to the abdominal wall; luid posterior to the right lobe of the liver must be in the pleural space.

reliable in differentiating exudate from transudate remains controversial. In their study of 100 patients, Abramowitz et al.1 concluded that attenuation values of pleural luid do not reliably differentiate exudate from transudate. Additional features such as luid loculation, pleural thickening, and pleural nodules were more commonly present with exudative effusion, but these indings were not statistically signiicant. Yildiz et al.125 asserted that this study’s conclusions may have been confounded by relatively low numbers of organizing consolidated effusions and inadequate statistical power. A study of 106 patients by Cullu et al.24 reached a differing conclusion, that exudates had a signiicantly higher median attenuation value (12.5 HU) than transudates (5 HU). Though there was signiicant overlap between exudates and transudates, it was concluded that a discriminatory value of 15 HU or greater is useful for identifying exudates. Aquino et al.3 determined that parietal pleural thickening is 96% speciic for exudate in the setting of pleural effusion and that exudate without parietal pleural thickening is most common in malignancy and uncomplicated parapneumonic effusion. Outside the realm of exudative versus transudative effusion, CT is capable of identifying blood (hemothorax), enhancing septations or nodules (infection, malignancy), and gas (instrumentation, esophageal rupture, bronchopleural istula [BPF], infection). The presence of small locules of gas in the pleural space is expected after pleural intervention but is speciic for infection in other contexts.51 MRI. MRI plays a limited role in the evaluation of pleural effusions, especially in benign disease, but may add value in cases where rib or chest wall invasion by the underlying process is suspected.51 Subacute or chronic hemothorax has high signal intensity on T1- and T2-weighted images. In chronic hemorrhagic effusion, there may be a concentric ring sign caused by peripheral hemosiderin (dark on T1- and T2-weighted images) and central methemoglobin (bright on T1- and T2-weighted images).79 Though chylothorax usually appears as a simple pleural effusion on all modalities, there have been reports of high signal intensity on T1-weighted MRI.79 MRI is sensitive for pleural septations and may be useful when cross-sectional imaging is needed but iodinated contrast is contraindicated. Simple luid demonstrates low signal intensity on T1-weighted imaging and high intensity on T2-weighted imaging. Triple-echo pulse sequences have been used to differentiate complex exudate (containing

malignant cells or infection, highest signal) from simple exudate (no malignant cells or infection, high signal) and transudate (low signal).26 In their evaluation of 57 patients with pleural effusion using DWI, Baysal et al.8 found that the mean apparent diffusion coeficient (ADC) value of exudative effusions was lower than that of transudative effusions, with an optimum cutoff value of 3.38 × 10−3 mm2/sec, yielding 91% sensitivity and 89% speciicity. In their study of 58 pleural effusions, Inan et al.56 reached similar conclusions. With current technology, however, routine use of MRI for this application is not feasible owing to factors including expense and technical limitations in scanning tachycardic, dyspneic, and critically ill patients.51 Pleurodesis. Pleurodesis is therapeutic sealing of the pleural space by inciting an organizing inlammatory reaction that causes the visceral and parietal pleura to adhere to one another. The usual indications are recurrent pneumothorax and recurrent malignant effusion. Talc has been found to have higher success rates and a lower rate of systemic complications than the chemical agents bleomycin and tetracycline (doxycycline is the most commonly used agent in the tetracycline class).29,48 The agent is applied as an aerosolized powder at thoracoscopy or thoracotomy (poudrage) or at the bedside as slurry instilled via a chest tube.27,48,76 The major complications of talc pleurodesis are acute pneumonitis, acute respiratory distress syndrome (ARDS), and pulmonary edema.13,27,50 Following pleurodesis, the organizing phase is characterized on radiographs as pleural thickening and loculation.123 Over half of patients have visible pleural thickening on long-term follow-up imaging.80 Following talc pleurodesis, CT usually shows pleural thickening and nodularity, with some residual loculated effusion and dependently located high-attenuation foci along both the visceral and parietal pleura that may mimic pleural calciication.93 The highattenuation foci may also be located in the issures.89 Areas correlating with these high-attenuation foci may have markedly increased FDG uptake on PET imaging that can simulate malignancy and persist for many years66 (Fig. 39-10). Aggressive antibiotic therapy is necessary in empyema. Surgical decortication may be helpful in patients who do not respond to antibiotics or in cases of moderate or large empyema and may include a Clagett window procedure, in which a small thoracotomy is left open for ongoing irrigation with antibiotic solution and drainage. When infection has resolved and granulation tissue has formed, antibiotic solution is instilled into the pleural space and the window may be closed using muscular laps from the latissimus dorsi (Fig. 39-11).

Pleural Infection: Parapneumonic Effusions and Empyema. Although approximately 40% of patients with pneumonia develop an associated parapneumonic effusion, only about 10% develop an empyema, which is deined as a purulent pleural collection. Pneumonia is the most common cause of empyema. Other causes include lung abscess, BPF, esophageal perforation, complications of surgery, and trauma.78,127 The evolution of empyema in three stages is summarized in Table 39-4.64,72,127 If each stage is not treated adequately, there is progression to the next stage. Imaging of empyema. As previously discussed, radiography and ultrasound are the modalities of choice for initial evaluation of pleural effusion. On plain radiographs, lenticular biconvex shadows rather than meniscoid shape suggests loculation and empyema rather than layering effusion. Loculated effusions do not layer on supine or decubitus views. Contrast-enhanced CT is a vital adjunct to pleural luid analysis in managing patients with infected effusions or empyema and is highly accurate in differentiating empyema from lung parenchymal abscess abutting the pleura.64

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B FIG 39-10 A, Axial CT image in a patient with left-sided talc pleurodesis shows subtle high density within the left-sided pleural thickening. B, Axial fused PET-CT image showing diffuse increased FDG uptake, which is more likely to be related to post-pleurodesis inlammation than tumor. It is important to note that radiotracer uptake due to inlammation cannot be deinitively differentiated from uptake by tumor.

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B FIG 39-11 A, Axial CT image showing a bronchopleural istula in the left upper thorax and a nonresolving left upper lobe pneumonia. B, Postsurgical débridement and a Clagett window and (C) post closure of Clagett window with a latissimus dorsi lap after the infection healed.

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B FIG 39-12 A, Axial CT image in a patient with right upper lobe necrotizing pneumonia with evidence of irregular cavitation within a right upper lobe consolidation. B, Another patient with an evolving right lower lobe pneumonia and a right hydropneumothorax with subtle pleural thickening, suggestive of an empyema.

Three Stages of Evolution of a Parapneumonic Effusion into Empyema

TABLE 39-5

1. First or “exudative” stage

Empyema

Parenchymal Abscess

Thin, uniform-thickness walls Smooth luminal and exterior margin Split pleura sign present Obtuse angle with chest wall Lenticular shape Compression rather than obliteration of lung structures Increased attenuation of extrapleural fat

Thick walls of nonuniform width Irregular luminal and exterior margin

TABLE 39-4

2. Second or “ibropurulent stage”

3. Third or “pleural peel”

• Exudative sterile effusion due to lymphovascular leakage from the pulmonary interstitium into the pleural space • Appropriate treatment includes antibiotics and drainage. • Effusion becomes infected (complicated effusion) and loculations develop. Effusion containing neutrophils is known as empyema. • Appropriate treatment includes antibiotics and drainage. • Fibroblasts migrate from the pleura into the empyema and create a ibrous pleural peel that may restrict lung movement. • Appropriate treatment includes antibiotics and open thoracotomy or video-assisted thorascopic surgery (VATS) decortication.

Differentiation of abscess from empyema is important because attempted drainage of parenchymal abscess may seed the sterile pleural space with bacteria, whereas drainage is a mainstay of therapy for empyema. CT features differentiating empyema from parenchymal abscess are summarized in Table 39-56,79,111,122 (Fig. 39-12). A classic contrast-enhanced CT sign of empyema is the split pleura sign, which describes thickened, enhancing visceral and parietal pleural layers separated by low-attenuation effusion.64 Pleural thickening and enhancement characterizes 86% to 100% of cases of empyema as opposed to only 60% of parapneumonic effusion.3,6 Increased attenuation of the extrapleural fat (>50 HU greater than subcutaneous fat) is an associated inding that may persist for a period of time following resolution of infection.6,59,122

CT Features Differentiating Empyema from Parenchymal Abscess

Split pleura sign absent Acute angle with chest wall Round shape Abrupt vessel cutoff and presence of bronchi at interface with normal lung Normal attenuation of extrapleural fat

Ultrasound is more sensitive than CT in detecting septations and is often used to guide intervention; CT is capable of detecting separate loculations of pleural luid (inferred by trapped gas pockets within the collection rather than by visualization of the septa themselves) in approximately 20% of cases.25 CT is useful to guide thoracentesis or drainage catheter placement when ultrasound is not feasible because of large patient body habitus or poor visualization of critical structures owing to air in the lung parenchyma or adjacent bony structures.127 Radiography and CT play complementary roles in assessing appropriate catheter positioning after placement and in cases where catheter drainage has ceased or the patient is not responding to therapy. MRI is rarely needed for routine evaluation of empyema. Relative weaknesses as compared with CT are inferior spatial resolution and susceptibility to artifacts; however, MRI is sensitive for demonstrating septations within pleural collections and may be a useful alternative in patients with contrast allergies or in contexts where avoidance of ionizing radiation exposure is desired. Rarely malignancies such as non-Hodgkin’s lymphoma, squamous cell carcinoma, sarcoma, and mesothelioma arise in chronic empyema cavities. MRI, because of to

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B FIG 39-13 A, Axial CT image showing bilateral pleural plaques—both calciied and noncalciied—in a patient with asbestos exposure. B, Diffuse pleural thickening with dystrophic calciication in a patient with left-sided pleural metastasis from osteosarcoma.

its excellent contrast resolution, is the modality of choice for differentiating neoplasm from ibrotic tissue.86

hemothorax, and pyogenic or mycobacterial infection. Prior talc pleurodesis should also be considered in the differential diagnosis for high-density material in the pleural space (Fig. 39-13).

Bronchopleural Fistula. BPF is deined as a direct communication between the bronchial tree and the pleural space that may occur spontaneously, as in cases of necrotizing pleural infection or malignancy, or as a result of trauma or iatrogenic injury. BPF is associated with high morbidity and mortality. Central BPF is a connection between a central large bronchus and the pleural space, whereas peripheral BPF is a connection between a peripheral airway and the pleural space. The most common causes of central BPF are dehiscence of a bronchial stump after lung transplantation or pneumonectomy, and trauma. Peripheral BPF is caused by necrotizing pneumonia, empyema, trauma, ruptured bullae, and iatrogenic injury from radiation therapy or thoracentesis. On radiography, increasing volume of pleural air (without a history of instrumentation), mediastinal shift, and loss of luid in a previously illed or illing postpneumonectomy space are indirect signs of BPF. New gas within an empyema may also suggest the diagnosis. CT with IV contrast is the modality of choice in suspected BPF, given its ability to depict the vasculature and evaluate for the underlying cause. Indirect indings on CT are analogous to the previously described radiographic indings. Direct indings of BPF include the istulous connection itself or extraluminal air bubbles adjacent to the bronchial stump. Multiplanar reformation and advanced postprocessing techniques (e.g., volume rendering, virtual bronchoscopy, MIP, MiniP imaging) are valuable in the evaluation of BPF.40 Demonstration of inhaled radiotracer (e.g., xenon) in the pleural space on ventilation scintigraphy may be useful in cases of occult BPF.40 Treatment of central BPF includes broad-spectrum antibiotics, protection of the contralateral lung from spilled pleural luid by appropriate patient positioning, drainage or surgical washout of the pleural space, and primary repair of the bronchial stump in postpneumonectomy patients (sometimes with reinforcement using omentum or other vascularized soft tissue). The goal of interventional therapy for peripheral BPF is pleural apposition, which is accomplished by thoracostomy, decortication, pleurodesis, and open drainage, or transbronchial occlusion using muscle laps, ibrin sealants, coils, stents, and one-way valves.40

Pleural Calciications. Pleural calciications may be seen in numerous conditions, including asbestos-related pleural disease, resolved

Diffuse Pleural Thickening. Diffuse ibrous pleural thickening, likely a reaction to chronic inlammation of the visceral pleura that results in fusion of the parietal and visceral pleura, is seen in a number of disease states. It is especially common in diseases that cause exudative pleural effusion.104 Tuberculous or bacterial empyema, hemothorax (especially posttraumatic), talc pleurodesis, asbestos exposure, radiation therapy, and some medications are the most common causes. Pleural thickening related to asbestos exposure and malignancy is discussed subsequently. On radiographs, pleural thickening may be indistinguishable from effusion. Typical indings include blunting of the costophrenic sulci, a several millimeter-thick soft tissue density stripe separating the lungs from the adjacent chest wall, thickened soft tissue internal to the ribs in patients with pneumothorax, pleural calciication, and asymmetric increase in low-attenuation extrapleural fat.123 When radiographs raise suspicion for diffuse pleural thickening, CT is useful for distinguishing thickened pleural from prominent extrapleural fat and malignant disease. On CT, pleural thickening may be seen as a soft tissue density stripe at least 1 mm in thickness internal to the ribs, innermost intercostal muscles, and paravertebral regions.123 The appearance of the thickened pleura itself is nonspeciic, and evaluation of patient exposure history (e.g., tuberculosis, asbestos) and assessment of the chest wall and lungs by CT is often necessary to narrow the differential diagnosis. Pleural thickening should be evaluated at several levels and outside the paraspinal region, where intercostal vessels and normal thickened fat may be dificult to distinguish from the pleura.91 Mimics of pleural thickening include the normal subcostalis and transverse thoracis muscles, and intercostal veins.123 In patients without a history of asbestos exposure, ancillary indings in the chest wall and lungs may permit accurate diagnosis. For example, presence of rib fractures and normal lung parenchyma may suggest pleural thickening due to prior hemothorax, whereas postinfectious (including posttuberculous) pleural thickening may have volume loss, extrapleural fat thickening, or parenchymal scarring. After talc pleurodesis, high-attenuation talc between the thickened visceral and parietal pleura (usually in the posterior thorax) creates the talc sandwich sign.89

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Erdheim-Chester disease (ECD) is a rare idiopathic form of non– Langerhans cell histiocytosis that may cause diffuse pleural thickening. The most typical presentation is bone pain with symmetric osteosclerosis of the metadiaphyses of the long bones.14 Thoracic involvement is seen in about 15% to 30% of cases.30,121 In their study of 40 patients with thoracic manifestations of ECD, Brun et al.14 reported perivascular and mediastinal iniltration, pericardial effusion and thickening, ground-glass opacities and poorly deined pulmonary nodules, pulmonary cysts, pleural effusions, and pleural thickening.

Benign Asbestos-Related Pleural Disease. Asbestos is a naturally occurring substance with ire-resistant properties that has been used in many industrial applications including building insulation, manufacturing, and shipbuilding. Inhalation of asbestos ibers has been associated with benign and malignant pleuropulmonary diseases such as formation of ibrous pleural effusions, pleural plaques, diffuse pleural thickening, round atelectasis, lung cancer, and malignant mesothelioma.104 Many pathologic entities related to asbestos exposure tend to manifest in a delayed fashion, with latency of up to 60 years.

Asbestos-Related Pleural Effusion. Benign hemorrhagic exudative pleural effusions are the earliest manifestation of asbestos-related pleural disease, appearing within 10 years of exposure. Risk of pleural effusion appears to be dose dependent. Asbestos-related effusions may be asymptomatic. They tend to resolve over months but may persist or recur. Development of diffuse pleural thickening often follows.104 Pleural Plaques. Pleural plaques are discrete areas of ibrosis that arise more commonly from the parietal than visceral pleura, appearing 20 to 30 years after exposure. They are the most common manifestation of asbestos-related pleural disease and are usually asymptomatic.104 Asbestos ibers are long and thin; therefore they are not cleared by macrophages or lymphatics. They tend to remain in the lower lung zones where ventilation is higher than in the upper lung zones. Thus, distribution of asbestos-related lung disease is predominantly basal. The anterior and lateral chest wall have greater excursion with respiration than the posterior chest wall, which is relatively ixed to the spine.38 Together, these attributes have led some to speculate that the reason asbestos-related pleural plaques form preferentially in the basal anterior and posterolateral chest is because of greater chest wall motion and hence more friction, leading to more irritation of the pleura by asbestos ibers. On radiographs, pleural plaques appear as opacities that demonstrate the incomplete border sign. They are most commonly identiied at the posterolateral chest wall and against the mediastinum and diaphragm, where thick lat opacities are virtually pathognomonic for asbestos-related pleural plaques. The apices and costophrenic sulci tend to be spared, unlike in diffuse pleural thickening. Calciication, present in 10% to 15% of cases, increases conspicuity. The holly leaf sign describes the appearance of pleural plaques as irregular in shape with angular outer contours.23,104 CT is more sensitive than radiography and reveals additional anterior and paravertebral plaques that may not be detected on radiographs. CT is also helpful in distinguishing pleural disease from extrapleural fat. Plaques involving the visceral pleura are sometimes called hairy plaques because of their association with short interstitial linear opacities in the adjacent lung parenchyma that appear to radiate from the plaque104 (Fig. 39-14).

Diffuse Pleural Thickening from Asbestos. In patients with a history of asbestos exposure, diffuse pleural thickening is less common

than focal pleural plaques, occurring in less than 10%. Incidence is, on average, 20 to 40 years after initial exposure. A dose-dependent relationship has been described.57,84 Presenting symptoms include progressive dyspnea and decreased exercise tolerance. Extensive pleural thickening is associated with restrictive physiology, which is relected by pulmonary function testing in affected patients. Pulmonary function testing abnormality has been shown to correlate with the degree of pleural thickening.21 For the diagnosis of diffuse pleural thickening, CT is more sensitive and speciic than radiography.104 The CT appearance of diffuse pleural thickening in patients with a history of asbestos exposure has been described by McLoud et al.82 as smooth, uninterrupted pleural opacity extending over at least one quarter of the chest wall, with or without obliteration of the costophrenic angle. Calciication is more rare in diffuse pleural thickening than in focal pleural plaques, and diffuse pleural thickening more often involves the apices and costophrenic angles. Unlike diffuse pleural thickening, nonconluent plaques do not extend over more than four interspaces, and diffuse pleural thickening may involve the interlobar issures, whereas plaques typically do not.104 Reactive proliferation of extrapleural fat is a common associated inding. Ninety percent of patients with diffuse pleural thickening due to asbestos exposure have associated parenchymal abnormalities. Diffuse pleural thickening due to asbestos exposure is more often bilateral than pleural malignancy and lacks iniltration and nodularity.

Round Atelectasis. Round atelectasis associated with asbestosrelated disease, also known as asbestos pseudotumor, is thought to occur as a result of pleural inlammation and ibrosis that results in infolding into the lung parenchyma, which becomes trapped and atelectatic.104 The classic radiographic appearance on chest radiographs is a masslike opacity with a broad-based interface with thickened pleura, associated with bronchovascular comet tails. The presence of volume loss rather than mass effect may favor this diagnosis over true masses such as lung cancer, the primary and most feared differential diagnosis. Contrast-enhanced CT is helpful for further characterization and shows uniform enhancement of the atelectatic lung (though this is not a reliable feature for distinguishing atelectasis from lung cancer). Given the sometimes nonspeciic appearance of round atelectasis and the primary differential consideration of lung cancer, biopsy or demonstration of stability or shrinkage on serial interval follow-up may be necessary to conirm the diagnosis.104 On T1-weighted MRI, atelectasis may appear as a mass with signal characteristics similar to those of liver tissue. MRI may also demonstrate the relationship of the pseudomass with bronchovascular structures. Curvilinear hypointense lines are thought to represent thickened indentations of visceral pleura.104,120

Pleural Masses and Malignant Pleural Disease Distinguishing malignant from benign disease

CT. Contrast-enhanced CT has been shown to be a moderately sensitive and highly speciic modality for differentiating benign from malignant pleural disease. It is useful for searching for primary malignancy in cases of metastasis of unknown primary and assessing for locoregional or extrapleural metastatic spread. CT features that favor malignant over benign pleural disease with their respective test characteristics are summarized in Table 39-6.69,83 In their study of 215 patients, Metintas et al.83 noted that invasion of the pericardium, chest wall, diaphragm, or mediastinum with pleural disease and nodular involvement of issures was not seen in any cases

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FIG 39-14 PA (A) and lateral (B) radiographs showing bilateral pleural plaques. C and D, Axial CT images showing consolidative opacities in the right lower lobe and left upper lobe that are characterized by round, masslike shape, associated bronchovascular “comet tails”, and broad-based interfaces with thickened adjacent pleura.

CT Morphologic Characteristics of Malignant Pleural Disease TABLE 39-6 CT Feature Pleural thickening >1 cm Involvement of mediastinal pleura Pleural nodularity “Rindlike” or circumferential pleural thickening

Sensitivity

Speciicity

36%-47% 56%-70% 38%-51% 41%-54%

64%-94% 83%-88% 94%-96% 95%-100%

of benign disease. The presence of calciication, for which CT is more sensitive than MRI, has been shown to be highly speciic for benign disease.54,69 PET-CT. FDG PET-CT has been shown to be highly accurate in differentiating between malignant and benign pleural disease;

however, false-positive results may be seen in cases of infection, uremic pleuritis, and pleurodesis, and false-negative results may occur in cases of solitary ibrous tumor of the pleura and low-grade lymphoma.31,44,63 MRI. Given the excellent discriminating ability of CT, MRI is considered a problem-solving modality for distinguishing malignant from benign pleural disease. In their study of 42 patients, Hierholzer et al.54 showed MRI combining signal and morphologic characteristics to be highly sensitive (100%) and speciic (93%) for malignant pleural disease. MRI is useful in surgical planning, given its excellent ability to detect diaphragmatic and chest wall invasion, which are reliable indicators of malignancy even in the absence of the classic morphologic characteristics described above.44,54 Morphologic characteristics that predict malignancy are similar between CT and MRI.54 Hypointensity of pleural disease relative to the intercostal muscles on T2-weighted sequences has been shown to reliably predict benignity, whereas malignant disease generally

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demonstrates T2 prolongation.35,36 Contrast-enhanced T1-weighted images are best for detecting chest wall, abdominal, and diaphragmatic invasion.44,54 In their study comparing PET-CT and DWI-MRI for differentiating malignant from benign pleural disease, in 31 patients, Coolen et al.20 reported an optimal ADC threshold of 1.52 × 10−3 mm2/ sec. DCE MRI raised both sensitivity and speciicity.

Benign pleural masses

Solitary ibrous tumor of the pleura. Solitary (or localized) ibrous tumor of the pleura (SFTP) is a rare neoplasm of mesenchymal origin that may be benign (≈80%) or malignant (≈20%).105,107 Histologically identical tumors are also found in extrathoracic sites. Small SFTPs are usually discovered incidentally in asymptomatic patients, but larger lesions may present with chest pain, cough, dyspnea, or a pressure sensation. Hypertrophic pulmonary osteoarthropathy is the most common paraneoplastic syndrome, seen in up to 22% of affected patients.105 Rarely these tumors express insulinlike growth factor (IGF)-2 and thus are associated with hypoglycemia.44 The imaging appearance of SFTP depends on size. Radiographically, these lesions are usually smooth or lobulated. When they abut the diaphragm, their appearance may simulate diaphragmatic eventration. In 40% of cases, lesions are pedunculated and hence mobile. Small effusions may be present.106 The typical CT appearance is of a homogeneous, well-circumscribed, noninvasive mass of soft tissue attenuation. Large lesions may have areas of myxoid change, hemorrhage, necrosis, or cystic degeneration, and many of these contain calciications.105 CT may show the lesion to be within a issure. Small lesions typically form obtuse angles with the pleural surface; large lesions may form acute angles and mimic a subpleural pulmonary mass. Regardless of whether the angle is acute or obtuse, the lesion usually has a smooth, tapering margin with the pleura. If an SFTP originates from the mediastinal pleura, it may mimic a mediastinal mass.75 Malignant lesions are more often sessile and atypically located, with necrosis and hemorrhage.105 On MRI, SFTP generally follows a pattern consistent with ibrous tissue—lesions tend to be low to intermediate signal on T1-weighted, T2-weighted, and proton density images. Areas of necrosis or myxoid change may be denoted by high signal on T2-weighted images. Intense homogeneous enhancement is typical, and the lesion may have a rim of low signal on T2-weighted images.18,44 On PET imaging, FDG uptake tends to be minimal.105 Core needle biopsy often does not yield suficient tissue for deinitive diagnosis107; thus excision is the treatment of choice for both malignant and benign SFTP105 (Figs. 39-15 and 39-16). Lipoma. Lipomas are rare in the pleura and show characteristics of fat on all imaging modalities. Pleural lipomas are minimally complex, homogeneous, circumscribed, fat-attenuation lesions on CT. On MRI they are hyperintense on T1- and moderately intense on T2-weighted images, with suppression on fat-saturated sequences and chemical shift artifact at their interfaces with luid-rich tissues (Fig. 39-17).44 Pleural metastases and malignant effusions. Metastatic disease is more common than primary pleural malignancy. Approximately 25% of all pleural effusions in elderly patients are malignant, and effusion is the most common inding in patients with pleural metastasis.12 The most common primary tumors that produce pleural metastases are lung, breast, ovarian, and gastric carcinomas, and lymphoma. Renal cell carcinoma and melanoma also have a propensity to metastasize to the pleura.12 Spread to the pleura may be direct (e.g., in cases of peripheral lung cancer), lymphatic, or hematogenous. Rarely thymic carcinoma and lymphoma may spread directly to the pleural space from the anterior mediastinum.44 Metastatic disease may present as solitary implants on the costal, diaphragmatic, or mediastinal pleural surface or in the interlobar is-

sures. Contrarily it may be a circumferential rind that may be indistinguishable from mesothelioma12 (Figs. 39-18 and 39-19). Malignant pleural mesothelioma. Malignant pleural mesothelioma (MPM) is an aggressive tumor arising from the parietal pleural surface. Though MPM was once a rare malignancy, worldwide incidence is increasing, most likely due to exposure to carcinogenic asbestos ibers, a known risk factor. Incidence is expected to peak from 2015 to 2020. The most common clinical presentation is an elderly male with pleural effusion and pleuritic chest pain who has a history of exposure to asbestos.106 Focal mass and advanced disease indistinguishable from advanced lung cancer are more rare presentations. Disease is dificult to manage and prognosis is poor, with median survival of 9 to 17 months after diagnosis.117 There are three histologic subtypes of MPM with different biological behaviors and natural histories. Epithelioid mesothelioma is the least aggressive and has the best prognosis; sarcomatoid and mixed (“biphasic”) tumors are often metastatic at the time of presentation.45 Histologically, sarcomatoid MPM possesses higher cellular and microvascular density and larger nucleus-to-cytoplasmic ratios than epithelioid subtypes.47 The risk of tumor seeding with nonexcisional biopsy has prompted development of imaging tests that can predict tumor characteristics noninvasively20 (Fig. 39-20).

Imaging in the diagnosis and staging of malignant pleural mesothelioma Radiography. The radiographic appearance of MPM is nonspeciic. Findings include pleural effusion, lobulated pleural thickening, or frank pleural masses. Coexistent pleural plaques may limit radiographic evaluation.45 Ultrasound. Ultrasound may be useful in the diagnosis of MPM by guiding and thus increasing the diagnostic yield of biopsy, but it is not useful for the more global evaluation afforded by cross-sectional imaging.45 CT. For diagnosis, staging, and monitoring of response to therapy in MPM, CT is the modality of choice. CT indings include unilateral pleural effusion (74%), circumferential nodular pleural thickening (92%), and thickening of the interlobular septa (86%).34 Tumor tends to develop at the diaphragmatic surface and grow upward.45 In some cases MPM presents with localized pleural masses rather than circumferential pleural thickening.106 There is often volume loss in the affected hemithorax, which has been termed the shrinking lung sign.4 In advanced disease, tumor may invade adjacent structures or metastasize to the lymph nodes, bones, lungs, or distant sites. Volume-rendered 3D CT images may show the relationship of tumor to critical structures and are often used for patient education and surgical planning. Other advanced CT techniques are also coming into widespread use, including volumetric analysis with serial segmentation and perfusion CT.45,100 DCE “perfusion” CT can be used to measure blood low dynamics and capillary permeability, thereby evaluating microvascularity of tumors before and after treatment.45 CT does not assess nodal disease accurately, because nodal size does not correlate with tumor involvement.5 The most commonly used tumor, node, metastasis (TNM) staging system for CT and MRI was proposed by the International Mesothelioma Interest Group (IMIG) in 1995. Determination of resectability varies among institutions and is often considered on a case-by-case basis. Features that suggest unresectability include extensive chest wall invasion, mediastinal invasion, mediastinal lymph nodal involvement, and intraabdominal or distant metastatic disease.45 Other staging paradigms, including the Brigham and Women’s Hospital staging system, are also in use.113 Deinitive staging of T1- and T2-stage disease by the IMIG TNM system using current imaging technology is not possible given that the visceral and parietal pleurae cannot be distinguished, and all

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E FIG 39-15 A, PA view of the chest in a patient with ibrous tumors of the pleura showing large, lobulated left chest masses. B, Axial CT image showing a mass abutting the left posterior pleura and a partially imaged issural mass. C and D, Axial T1- and T2-weighted images showing that the masses are isointense to muscle and (E) showing heterogeneous enhancement of the issural mass and peripheral enhancement and central necrosis of the posterior pleural mass.

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D FIG 39-16 MRI images in a patient with malignant ibrous tumor of the right pleura. A, Axial T1-weighted image shows right issural tumor isointense to muscle. B and D, The mass enhances. C, Coronal T2-weighted image shows the mass to be hyperintense to muscle.

modalities are relatively insensitive for nodal disease.12,101 Cervical mediastinoscopy with biopsy has been shown to be more sensitive and speciic for nodal disease than CT and has been recommended when radical surgery is being considered.108,119 Currently, the International Association for the Study of Lung Cancer (IASLC) is developing a new staging system that accounts for factors such as the differing biological behavior of epithelioid and nonepithelioid cancers118 (Figs. 39-21 and 39-22). MRI. As previously discussed, MRI has advantages over CT in differentiating malignant from benign pleural disease. In addition, MRI is useful for conirmation and further evaluation of CT indings.44 Given its higher signal-to-noise ratio, MRI is superior in detecting chest wall and diaphragmatic involvement, particularly with contrastenhanced T1-weighted sequences with fat suppression.4,45 MRI may reclassify about 30% of surgical candidates into an inoperable stage.112 MPM is iso- to slightly hyperintense relative to adjacent chest wall musculature on T1-weighted images and moderately hyperintense on T2-weighted images. IV gadolinium increases conspicuity of tumor.44

Sagittal and coronal images are most useful for delineating tumor breach of the diaphragm and mediastinal and chest wall involvement— factors that decrease resectability.45 DCE (perfusion) MRI may allow noninvasive distinction among histopathologic subtypes and evaluate microvascularity in a manner analogous to CT perfusion.4,45 Perfusion MRI has been shown to be capable of predicting therapeutic eficacy of chemotherapy in unresectable disease.45 Cine imaging techniques with high temporal resolution evaluate tumor mobility and lung motion (e.g., parallel MRI using fast imaging with SSFP), permitting identiication of subtle mediastinal and chest wall invasion.44 DWI with ADC correlation has been shown to relect the histologic differences between epithelioid and nonepithelioid subtypes, with higher intensity on DWI and lower ADC values found in sarcomatoid tissue, denoting edema, higher cellularity, and higher nuclear-to-cytoplasmic ratios.47 The pointillism sign, named for the postimpressionist painting style, describes the appearance of discrete high-intensity foci on high b-value DWI that likely represent multifocal tumor deposition. This sign has been shown to be highly sensitive (92%) and speciic (86%)

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B FIG 39-17 A, PA view of the chest showing a pleural lesion in the right upper chest incidentally seen in a patient with right lower lobe pneumonia. B, Axial CT image showing a fat-containing right upper pleural lesion, consistent with lipoma.

A

B FIG 39-18 A, Coronal postcontrast VIBE image showing a solitary right pleural metastasis from melanoma. B, Coronal T2-weighted MRI showing diffuse right pleural metastases from lung adenocarcinoma, with nodular pleural thickening and a large loculated right pleural effusion.

1111

A

B FIG 39-19 A, Diffuse metastases from osteosarcoma, with dystrophic calciication. B, Diffuse enhancing left-sided pleural tumor (metastatic thymoma).

A

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C FIG 39-20 A, Coronal postcontrast VIBE image showing left circumferential biphasic mesothelioma with apical involvement (arrow). Enhancement in the left lateral chest wall is due to recent surgical biopsy. B, Sagittal image showing the relationship of tumor to the diaphragm and issures; the patient underwent successful resection of mesothelioma. C, Volume-rendered image showing the resected gross pathological specimen.

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F FIG 39-21 A-F, Axial and coronal CT images in a patient with right-sided epithelioid mesothelioma with extensive nodal involvement. Note enlarged right and left paratracheal lymph nodes, subcarinal node, right internal mammary node, and pericardial and diaphragmatic nodes. Malignant and benign adenopathy from mesothelioma cannot be reliably differentiated by imaging, and sampling by cervical mediastinoscopy may be needed for accurate preoperative nodal staging.

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B FIG 39-22 A, Axial CT image showing focal invasion of the endothoracic fascia. B, Coronal image showing invasion of mediastinal fat medially and endothoracic fascia laterally.

for MPM and may be useful for guiding thorascopic evaluation4 (Figs. 39-23 through 39-27). PET-CT. Hybrid PET-CT has been used in the management of MPM to determine metabolic behavior and extent of tumor. The chief strength of PET-CT is its ability to detect occult metastatic disease that would not be apparent by other modalities but changes staging.4 FDG uptake may be moderate to high, depending on histologic subtype, with epithelioid tumors being less FDG avid than their sarcomatoid or biphasic counterparts.42,45 Primary tumors tend to be more FDG avid in higher-stage disease.41 Higher metabolic activity has been shown to portend poorer prognosis with shorter survival.4 PET may allow identiication of nodal disease not evident by CT and allow distinction of tumor from ibrosis, necrosis, and atelectasis45,106 (Fig. 39-28).

Treatment, assessment of treatment response, and postsurgical evaluation in MPM Treatment. Treatment decisions are tailored to each patient on the basis of tumor staging and operative risk. Surgical considerations in the management of MPM remain controversial, with a major distinction between palliative surgery and surgery with curative intent (maximal debulking surgery).118 Maximal debulking surgery can be subdivided into: (1) extrapleural pneumonectomy (EPP), in which the entire pleura, ipsilateral lung, and (if necessary) the pericardium and diaphragm are removed, with subsequent soft tissue patch reconstruction; and (2) pleurectomy/decortication (P/D), in which the ipsilateral lung is left in place.118 A recent study of 101 patients demonstrated that neoadjuvant chemotherapy, P/D, and adjuvant chemotherapy were superior to neoadjuvant chemotherapy, EPP, and adjuvant radiotherapy in terms of overall survival.67 Modern multimodality therapy may include combinations of surgery, systemic or heated intraoperative pleural chemotherapy, photodynamic therapy (in which the tumor is sensitized to visible light by a systemically distributed agent and subsequently exposed to light), intrapleural immunotherapy, and radiotherapy.39,114,118 Many clinical trials are ongoing. Assessment of treatment response. Volumetric analysis may be more useful in MPM than the Response Evaluation Criteria in Solid

Tumors (RECIST) and modiied RECIST criteria in evaluating treatment response in unresectable disease, given that MPM is nonspherical and grows along pleural relections, making it dificult to measure in orthogonal planes.45 Assessment for recurrence or progressive metastasis is generally with CT or PET-CT. CT indings of recurrence include enlarging soft tissue mass along the resection margin, ascites or peritoneal thickening indicative of abdominal disease, pulmonary nodules, and mediastinal lymphadenopathy.45 Postoperative granulation tissue along the resection margin is usually more irregular and nodular than recurrent tumor but is sometimes concerning. PET-CT is useful for distinguishing granulation tissue from recurrent tumor. Whereas FDG uptake in granulation tissue tends to decrease over time, tumor tends to have unchanging or increasing FDG uptake over serial studies.9 PET-CT is also used for semiquantitative comparison of pre- and posttreatment FDG uptake in tumor masses.45 Decrease in tumor microcirculation as measured by perfusion MRI has been shown to be linked to early clinical response and survival in MPM patients on chemotherapy43 (Fig. 39-29). Postsurgical evaluation. Following surgery, radiography is used routinely; CT is used when complications are suspected.45 After pneumonectomy, the pneumonectomy space ills with luid at a predictable rate, with opaciication of approximately one additional intercostal space every 7 days by chest radiography. If the rate of illing is excessive, hemorrhage or chyle leak due to damage to the thoracic duct should be suspected. MRI can be used to evaluate the thoracic duct prior to attempted corrective embolization in cases of chyle leak. Contrarily, a decrease in accumulated luid suggests development of a BPF or leakage into the abdomen via a defect in the reconstructed diaphragm.45 BPF tends to present within 1 week to 3 months after surgery.40 Management of BPF in the contexts of pneumonectomy and empyema is similar (Fig. 39-30). Herniation of the stomach into the thorax is a rare complication of left-sided pneumonectomy that may be complicated by strangulation.45 In the rare postpneumonectomy syndrome, extreme rotation Text continued on p. 1119

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E FIG 39-23 A-C, The diaphragm is clearly demonstrated as a black line on HASTE and an enhanced line on FS-T1-weighted images (arrows). A preserved fat plane is also clearly shown as a suppressed line. D, Epithelioid MPM with extension across the diaphragm. The line of the diaphragm is interrupted (white arrows). The subdiaphragmatic fat plane is also obscured by the mass (black arrows), indicating intraabdominal extension. E, Sagittal contrast-enhanced FS-T1-weighted image demonstrates hepatic involvement (small black arrow).

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FIG 39-24 Coronal subtraction image showing an irregular lateral contour of a right-sided mesothelioma, consistent with multifocal endothoracic fascial involvement.

A

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FIG 39-25 Comparison of CT and MRI images in a patient with left-sided sarcomatoid mesothelioma with left chest wall extension, left rib metastases, and intramural thrombus in the descending aorta. MRI is superior for detecting chest wall invasion, involvement of vascular structures, and bone involvement.

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E FIG 39-26 Patient with left sided Mesothelioma. A, T1-weighted axial image showing anterior chest wall invasion by the tumor, B, axial B1000 image, and C, an ADC map, with an ADC value of 0.883 × 10−3 mm2/ sec suggestive of sarcomatoid subtype. D, T2-weighted axial image and E, axial B500 image depicting the “pointillism sign”.

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AUC

A

B KTRANS

C

Ve

D FIG 39-27 Perfusion-weighted imaging in mesothelioma showing multiparametric maps. A, AUC (area under the curve); B, enhancement curve; C, Ktrans (transport coeficient); and D, Ve (elimination coeficient).

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A

B FIG 39-28 A and B, Fused 18F FDG PET-CT images in a patient with advanced epithelioid MPM, with avid left supraclavicular nodes, mediastinal nodes, and intraabdominal extension (arrows).

and shift of the mediastinum results in symptomatic central airway obstruction109 (Fig. 39-31). Primary pleural sarcoma. Primary sarcomas that involve the pleura are rare and include liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma, previously known as malignant ibrous histiocytoma. For all types, treatment includes resection, often with chemotherapy and/or radiation. Liposarcoma. Pleural liposarcomas are often asymptomatic and appear on CT as large iniltrative masses that usually contain fat, with prominent soft tissue components such as enhancing nodules or thick septa. On MRI, liposarcomas appear hyperintense on T2-weighted sequences owing to myxoid degeneration, which is common. On T1-weighted images, they tend to be hypointense, with variable enhancement after administration of contrast12,44 (Fig. 39-32). Synovial sarcoma. Thoracic synovial sarcoma is more rare than its extrathoracic counterpart and may arise in the chest wall, pleura, mediastinum, heart, or lung. Ipsilateral pleural effusions are common.

1119

On CT, pleural synovial sarcomas are noncalciied well-circumscribed masses that do not involve bone. The enhancement pattern is typically heterogeneous, and the tumor often contains areas of hemorrhage and necrosis. On MRI, nodular soft tissue with multiloculated luid-illed components is typical. Rim enhancement is seen following administration of IV contrast. Tissue heterogeneity is more evident by MRI than CT. In reference to synovial sarcoma the triple sign describes the presence of hyper-, iso-, and hypointense areas on T2-weighted MRI87 (Fig. 39-33). Undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is a malignancy of ibrohistiocytic origin that rarely involves the pleura. On CT, UPS is a somewhat nonspeciicappearing heterogeneously-enhancing mass. Calciication is unusual prior to treatment. The MRI appearance of UPS is a mass with intermediate to low signal on T1-weighted sequences and intermediate to high signal on T2-weighted sequences. Variably present ibrous tissue components include collagen (hypointense on all pulse sequences), myxoid stroma (hypointense on T1-weighted images and hyperintense on T2-weighted images), and hemorrhage92 (Fig. 39-34). Epithelioid hemangioendothelioma. Epithelioid hemangioendothelioma (EH) is a rare low- to intermediate-grade aggressive neoplasm that rarely arises in the pleura. It is more common in the bone, liver, soft tissue, and lung. The pleural form more commonly affects males than females. Presenting symptoms are somewhat nonspeciic and include chest pain, dyspnea, fever, and cough. Patients tend to present with advanced disease. Radiographic indings include pleural effusion and volume loss in the affected hemithorax. CT shows smooth and nodular pleural thickening, with or without invasion of the diaphragm or mediastinum. Pulmonary nodules or interstitial thickening indicate metastasis. As in other entities, MRI is superior for demonstrating invasion of the diaphragm and mediastinum, and PET-CT is useful for evaluating for occult metastasis. Overall the imaging indings are similar to those of MPM and pleural carcinomatosis. Given the rarity of the condition, no treatment regimen has been rigorously tested; to date, patients with EH have been treated with surgery and chemoradiation. The prognosis of pleural EH is poor (much worse than that of pulmonary EH), with a median survival time of 10 months after diagnosis.7,22,62 Pancoast tumors. Apical lung cancers are also known as Pancoast or superior sulcus tumors. The term Pancoast syndrome refers to shoulder and arm pain with or without ipsilateral Horner’s syndrome due to involvement of the lower cords of the brachial plexus and sympathetic chain by tumor.16 Chest wall invasion with rib destruction is common. Other critical structures that may be involved are the spine, subclavian vessels, and inferior neck.37,50 Pancoast tumors may be dificult to identify on radiographs because of obscuration by the overlying ribs and clavicles and resemblance to the virtually ubiquitous benign apical pleural cap. Bone destruction, present in approximately one third of cases, may be dificult to identify on plain ilms.96 The inding of an asymmetric or enlarging pleural cap should be regarded with suspicion, especially in a symptomatic patient.50 CT is helpful in differentiating the intrapulmonary mass from an apical pleural cap and identifying bone destruction and chest wall invasion.17,50 CT is also essential for staging; mediastinal adenopathy portends a poor prognosis.37 CT-guided ine needle biopsy is successful in establishing the diagnosis in more than 90% of cases.37 MRI is superior for evaluating the extent of tumor and involvement of the brachial plexus, subclavian vessels, neural foramina, spinal canal, and bone marrow. Coronal and sagittal T1-weighted and STIR sequences obtained with thin sections and surface coils are optimal. MR angiography is particularly useful for vascular assessment.37 Interruption of the normal extrapleural fat line over the lung apex indicates tumoral invasion.50

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B

A

Fused coronals

18

FIG 39-29 Coronal fused F FDG PET-CT images in a patient (A) before and (B) after neoadjuvant chemotherapy. Though the anatomic distribution of tumor is unchanged, signiicant decrease in radiotracer uptake indicates treatment response.

A

B FIG 39-30 Axial CT images in patient who has undergone extrapleural pneumonectomy. A, Near-complete illing of the pneumonectomy space with luid soon after surgery. B, Emptying of the space 7 days later secondary to a central bronchopleural istula.

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B

D FIG 39-31 Radiograph (A) and coronal CT image (B) showing gastric herniation into the left chest after left extrapleural pneumonectomy. C and D, In a different patient who has undergone right-sided pneumonectomy, C, demonstrates rightward shift of the mediastinum into the pneumonectomy space. D, demonstrates a radiodense implant subsequently placed in the right hemithorax to displace the mediastinum toward the left.

A

B FIG 39-32 A, In a patient with biopsy-proven dedifferentiated liposarcoma, an axial CT image shows a heterogeneous mass illing the right hemithorax. B, Coronal T2-weighted MRI shows the mass to be predominantly isointense relative to fat.

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D FIG 39-33 Axial T1-weighted (A), T2-weighted (B), and postcontrast T1-weighted (C) MRI images and (D) coronal postcontrast T1-weighted image in a patient with pleural synovial sarcoma showing nodular soft tissue with multiloculated luid-illed components. There is rim enhancement following administration of IV contrast, and tissue heterogeneity exemplifying the “triple sign” of hyper-, iso-, and hypointense areas on T2-weighted MRI.

Neoadjuvant chemoradiotherapy and en bloc resection have improved survival16,17,50 (Fig. 39-35).

CHEST WALL Approach to Imaging the Chest Wall Radiography. Though many chest wall masses are evaluable on physical exam, radiography may be useful to delineate the size, location, and growth rate of the mass. Furthermore, radiographs may characterize soft tissue calciication, tumor matrix, ossiication, and bone involvement. Low-kVp imaging (as used in bone radiography) is superior to high-kVp imaging (as used in chest radiography) for deining calciications and soft tissue planes in fat-containing tumors such as lipomas.115 Dedicated breast imaging is indicated for lesions involving the breasts.

Ultrasound. Ultrasound using a high-frequency transducer (e.g., 7.5-10 MHz) is useful for evaluating supericial chest wall and breast masses and is commonly used to guide biopsy.88,115

CT. CT provides detailed information about tumor morphology, tissue characteristics, location, and extent. Enhancement characteris-

tics may reine differential diagnosis. Performing the CT scan in a modiied scan plane and using multiplanar reformations may be useful when the lesion is supraclavicular or oriented parallel to the ribs.115 Particular strengths of CT with respect to chest wall masses are its ability to evaluate lesional calciication and bony involvement.88 CT may be useful to guide biopsy in cases of osteomyelitis involving the chest wall.19 In cases of destructive rib lesions, CT is superior to MRI in assessing cortical bone destruction. Several benign processes may simulate malignancy; for example, a subacute or old rib fracture may mimic a chondroid lesion or expansile neoplasm. Also, nonmalignant rib erosion may occur with benign processes such as granulomatous disease, radiation osteitis, and ibrous dysplasia.

MRI. MRI reines tissue characterization, allowing identiication of fat, vascularity, and other speciic features that narrow differential diagnosis, and is superior for evaluating transspatial lesions and neurovascular involvement.88 It is considered the imaging modality of choice for evaluation of chest wall lesions by some authors.115 Compared to CT, MRI is more accurate in assessing the extent of chest wall masses and bone marrow iniltration. Supericial coils are recommended for evaluation of chest wall lesions; torso coils are recommended for evaluation of lesions that involve deeper portions of the

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B FIG 39-34 Coronal CT (A), MRI (B), and PET-CT (C) images in a patient with undifferentiated pleomorphic sarcoma, showing a heterogeneous pleural and parenchymal mass within the right chest, with enhancement and diffuse and heterogeneous FDG uptake.

thorax.115 Fat suppression highlights focal enhancement on postcontrast T1-weighted images.

PET. FDG-PET provides information about the metabolic activity of a lesion, which is useful in assessment of metastatic or locally invasive lesions and guides biopsy to higher-yield cellular areas.88

Congenital Chest Wall Anomalies Congenital chest wall anomalies are briely summarized in Table 39-7.58 Radiographs and CT are commonly indicated for evaluation of these disorders (Figs. 39-36 through 39-38).

Infectious Conditions of the Chest Wall Primary chest wall infection is rare. Physical examination may underestimate extent, especially in immunocompromised patients. Risk

factors include diabetes mellitus, immunocompromise, trauma, and surgical instrumentation.19 Klebsiella pneumoniae and Staphylococcus aureus are the most common bacterial agents. In chest wall infection, ultrasound, CT, and MRI are complementary modalities. MRI is the modality of choice for speciic assessment of the soft tissues and can discern infected tissue from adjacent inlammation even without IV contrast, whereas CT is preferred for evaluating bony destruction. Multiplanar reformatted images in both modalities add valuable information about extent of infection and interspace communication within loculated collections and aid in surgical planning. Chest wall abscesses demonstrate low signal intensity on T1-weighted images and high signal intensity on STIR and T2-weighted images, with rim enhancement on postcontrast fat-saturated T1-weighted images. T1-weighted sequences are key for anatomic

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B

C

A

FIG 39-35 A, PA chest radiograph in a patient presenting with Horner’s syndrome, miosis, and right arm weakness, showing subtle right apical pleural thickening. B and C, Axial CT and MRI showing a superior sulcus mass with encasement of the right brachial plexus and blood vessels, consistent with an unresectable Pancoast tumor.

Congenital Chest Wall Anomalies TABLE 39-7 Pectus excavatum (funnel chest)

Pectus carinatum (pigeon breast) Cervical rib

Cleidocranial dysostosis Poland syndrome

• Depression of the sternum thought to be due to misdirected growth of the lower costal cartilages • Quantiied using the Haller or pectus index on CT imaging—calculated by dividing the transverse by the AP diameter of the chest. Normal value is ≈ 2.56, and a value > 3.25 necessitates surgical correction. • Outward bowing of the sternum • Sometimes isolated, commonly seen in patients with congenital heart disease • Supernumerary rib articulating with the lowest cervical vertebra • The true second rib articulates with the sternomanubrial joint. • Asymptomatic in 90% of cases but may be associated with thoracic outlet or PagetSchroetter syndrome. Dedicated vascular imaging with multiplanar reformatted images may be useful. • Defective development of many bones (pubic bones, long bones, vertebrae) including the clavicles, which are variably hypoplastic • Complete or partial absence of the pectoralis major • Associated with ipsilateral syndactyly, rib hypoplasia, and aplasia of the ipsilateral breast or nipple

assessment because of their superior spatial resolution; STIR and T2-weighted images add contrast resolution that is helpful for assessing abscess extent and location. CT is more sensitive for detecting gas and calciication and superior to MRI in differentiating among substances that cause susceptibility artifact (e.g., calcium, gas, blood products, and metallic surgical materials). Osteomyelitis is most commonly due to contiguous spread of pulmonary infection (tuberculosis, fungal infection) or empyema (termed empyema necessitatis). S. aureus and Pseudomonas aeruginosa are the most common causal organisms. Bone destruction is generally not evident by radiography for 1 to 2 weeks; CT and MRI are capable of identifying commonly associated soft tissue masses, effacement of deep soft tissue planes, and periosteal elevation.58 MRI is highly sensitive and speciic and thus considered the modality of choice for osteomyelitis involving the thoracic bones. Typical MRI indings include hypointensity against the high background signal of fat on T1-weighted images without fat suppression, corresponding high signal edema on luid-sensitive sequences, and focal enhancement. IV drug use, immunosuppression, and chronic renal failure predispose to sternoclavicular osteomyelitis.58 Subclavian venous catheter-associated infection by S. aureus is a common scenario in this type of infection, with standard treatment being removal of the infected catheter and IV antibiotics. Surgical resection is reserved for cases in which infection is shown to extend beyond the joint on imaging. Nonpyogenic infection of the chest wall is more unusual. Mycobacterium tuberculosis rarely involves the chest wall. Hematogenous seeding is more common than contiguous spread. Chest wall abscess and sinus tracts are seen in about 25% of cases. Destructive chest wall masses with calciication and rim enhancement on CT are typical.58 Nocardia asteroides and Actinomyces israelii are bacterial species that infect the chest wall by tracking through the tissue planes separating

Disease of the Pleura, Chest Wall, and Diaphragm

CHAPTER 39

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E

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F

G

H FIG 39-36 Axial (A), coronal (B), and volume-rendered images (C and D) of a patient with pectus excavatum. Axial (E), coronal (F), and volume-rendered images (G and H) after repair of pectus excavatum. Note the improvement in the chest deformity and displacement of the heart.

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FIG 39-37 PA radiograph of the chest showing cervical ribs (arrow).

the chest wall from the pleural space (empyema necessitatis). On crosssectional imaging, indings include soft tissue thickening and nonspeciic inlammatory changes, luid collections, draining sinus tracts, wavy periostitis, and rib destruction.58,60 Aspergillus fumigatus is a fungal species that produces multiple pulmonary manifestations. Chest wall invasion may occur, with osteolysis and istula formation58 (Fig. 39-39).

Chest Wall Masses Benign chest wall lesions typically present as slow-growing, minimally symptomatic palpable masses. Bone erosion without destruction, resulting from relatively long-standing pressure effects, suggests benignity.

Benign Chest Wall Masses. A convenient paradigm for evaluating benign chest wall masses classiies lesions by tissue origin. Lesions of bone and cartilaginous origin. Benign lesions of bone and cartilage that occur in the chest wall include ibrous dysplasia, enchondroma, osteochondroma, chondroblastoma, aneurysmal bone cyst, and giant cell tumor.58 These lesions are discussed in depth elsewhere. Tumors of adipocyte origin. Lipomas are the overall most common chest wall soft tissue tumors and also the most common benign chest wall mass.58 They are most frequently found in patients over age 50 years and are more common in obese patients. Chest wall lipomas tend to be deep seated, involving deep muscular and intermuscular layers, and less well circumscribed than lipomas elsewhere. In two thirds of cases, lipomas are composed solely of adipose tissue, but nonadipose tissue such as connective tissue septa and calciication is present in the remainder.

On CT, lipomas are circumscribed fat-attenuation lesions that lack enhancement. On MRI, lipomas follow fat signal intensity on all sequences, with suppression on fat-saturated sequences including STIR. There may be sparse ibrous septa that demonstrate low signal intensity on T1- and T2-weighted images and faint enhancement (n.b., thick, irregular, avidly enhancing septa or avidly enhancing nodules are concerning for malignancy).58,60 Chemical shift artifact at interfaces with more luid-rich tissues is characteristic. A rare variant is spindle cell lipoma, which arises in the subcutaneous tissues of the neck or shoulder in middle aged to elderly men, appearing as a 3- to 5-cm mass that is heterogeneous on both T1- and T2-weighted sequences.58 Evaluation of extent, local iniltration, and relationship with neurovascular structures by MRI is essential for surgical planning (Fig. 39-40). Vascular and lymphatic lesions. The term hemangioma encompasses many entities that can be classiied according to the predominant vessel type (arteriovenous, capillary, mixed vascular, cavernous [composed of dilated, tortuous, thin walled vessels], and venous). Many lesions include nonvascular tissues including fat, smooth muscle, thrombus, ibrous tissue, and hemosiderin. Phleboliths are most commonly seen in cavernous hemangiomas but may be seen in other lesions.92 Hemangiomas are rare in the chest wall and may be found in the synovium or musculature. These lesions usually present in the pediatric population. On CT, most cavernous hemangiomas appear as heterogeneously attenuating soft tissue masses. The heterogeneity is due to the presence of fat (which may represent a substantial portion of the lesion) and vascular or ibrous components. Background attenuation is similar to skeletal muscle.92 Slow-lowing blood in dilated vessels leads to the characteristic MRI appearance of poorly deined curvilinear structures that are low in signal on T1-weighted sequences, with high intensity on T2-weighted images. Enhancement is marked.92 Muscle atrophy may be observed with intramuscular hemangiomas. As they are elsewhere, arteriovenous malformations (AVMs) of the chest wall are characterized by tubular low voids. Glomus tumors most often present as painful solitary masses in adult patients. Less commonly, tumors are multiple and asymptomatic; rarely, glomus tumors are malignant. The neoplastic cells that comprise glomus tumors resemble smooth muscle cells of the normal glomus body. Lesions are often intramuscular. The typical appearance on CT is a soft tissue mass with adjacent osseous erosion. On MRI, the mass displaces major vessels and is surrounded by tortuous vessels arising from a vascular pedicle. Heterogeneous signal intensity and sharp interfaces with adjacent tissues after IV contrast administration are typical features.115 Lymphangiomas are uncommon hamartomatous lesions composed of dilated lymphatic vessels that most often present in early childhood as a neck mass that extends into the chest wall or axilla.92 Lesions are commonly present at the cervicothoracic junction in children and in the mediastinum in adults (probably because they are occult on physical exam).58,92 The constituent lymphatic channels are sequestered from the lymphatic system. MRI is the preferred imaging modality because CT appearance is nonspeciic. Lymphangiomas follow simple luid signal on all sequences, with thin peripheral and septal enhancement115 (Fig. 39-41). Peripheral nerve and nerve sheath tumors. Spinal nerve roots, intercostal nerves, and distal brachial plexus branches may give rise to neurogenic chest wall tumors. The appearance of these tumors in the chest wall is similar to their appearance in other locations. There is overlap in the imaging appearances of neuroibroma and schwannoma, but the imaging features discussed below are often helpful in distinguishing them from one another.

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A

B

C FIG 39-38 Axial CT images (A and B) and volume-rendered image (C) showing absence of left pectoralis major muscle in a patient with Poland syndrome.

A

B FIG 39-39 A and B, Axial CT images showing a right chest wall mycobacterial abscess and a sinus tract in the left anterior chest wall in an immune-suppressed patient.

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B

A

FIG 39-40 Prone axial CT image (A), coronal T2-weighted image (B), and coronal T2-weighted image with fat suppression (C) showing a right-sided elastoibroma dorsi.

B A

C FIG 39-41 Axial T1-weighted MRI pre- (A) and post contrast (B) and T2-weighted MRI (C) showing nonenhancing, tubular, dilated lymphatics with minimal peripheral enhancement in a patient with a slow-low right chest wall lymphatic malformation. Incidentally, a lesion is noted in the right lobe of the liver.

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F FIG 39-42 A, PA radiograph of a patient with a neurogenic tumor in the left posterior mediastinum. Axial CT (B) and PET image (C) showing avid posterior mediastinal mass; D-E, axial T1-weighted pre- and postcontrast images showing heterogeneous enhancement and F, Coronal T2-weighted image showing high signal representing myxoid degeneration.

Schwannomas are benign nerve sheath tumors that arise from spinal nerve roots or intercostal nerves. They tend to be slow growing and are most commonly seen in young to middle-aged adult patients. Small lesions are well circumscribed, but larger lesions may be more lobulated. Scalloping rather than erosion of adjacent bones is typical. The usual CT appearance of schwannoma is a homogeneous mass that is iso- or slightly hypoattenuating to muscle. A less common appearance is a cyst with ibrous walls, containing smaller nodules. Schwannomas tend to be isointense on T1- and markedly hyperintense on T2-weighted images, with avid enhancement. Tumors may

demonstrate the fascicular sign, with heterogeneous low signal intensity in a ringlike pattern. The nerve of origin may be identiiable. Degeneration—manifested as myxoid cystic change, hemorrhage, calciication, and ibrosis if present—is more common in schwannomas than in neuroibromas. Biopsy is painful owing to intrinsic innervation115 (Fig. 39-42). Neuroibromas may occur in isolation or in neuroibromatosis type 1 (NF1). Most affected patients present between the ages of 20 and 40. Typically, neuroibromas originate from spinal nerve roots and may be localized (most common), diffuse, or plexiform. Plexiform tumors

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C

FIG 39-43 Axial T1-weighted (A), T2-weighted (B), and postcontrast T1-weighted (C) MRI showing a hypointense, bilobed chest wall mass with intense enhancement post IV contrast administration, consistent with an ibroma dorsi.

involve long segments of nerves or multiple nerve branches. Like other slow-growing peripheral nerve tumors, they tend to remodel without eroding bone—for instance, expanding neural foramina when they arise from spinal nerve roots. Malignant degeneration occurs rarely but is more common in cases of NF1. Malignant degeneration may be suspected in cases of rapid growth.92 The CT appearance of neuroibroma is a low-attenuation heterogeneously enhancing lesion. On T2-weighted and postgadolinium T1-weighted images, a target appearance is typical. The center of the lesion is composed of ibrous stroma that is hypointense on T2-weighted images and demonstrates enhancement, and the periphery is composed of myxoid material that does not enhance signiicantly. Ganglioneuromas and paragangliomas arise from sympathetic nervous elements. Ganglioneuromas appear as sharply marginated, homogeneous or heterogeneous paravertebral masses that may be calciied. Curvilinear bands (ibrous tissue) that are hypointense on both T1- and T2-weighted images may give these lesions a whorled or septated appearance. Paragangliomas are more commonly right-sided paravertebral masses that occur in adolescents and young adults. They tend to be homogeneous and avidly-enhancing on cross-sectional imaging.92 Fibroblastic-myoibroblastic tumors. Elastoibroma dorsi is a relatively common muscular pseudotumor that occurs characteristically at the inferior angle of the scapula. These tumors are much more common in women and tend to occur in middle-aged to elderly patients; lesions are often asymptomatic and are commonly bilateral. These lesions share attenuation and intensity characteristics with muscle on CT and MRI, respectively, with interspersed fat giving a layered appearance.92 With typical imaging characteristics, biopsy may be avoided92,115 (Fig. 39-43). Fibromatosis, also known as desmoid tumor, is a benign true neoplasm composed of ibroblasts and collagenous matrix that arises from connective tissue or posttraumatic or surgical scars. Typically, ibromatosis is iniltrative and locally aggressive. Attenuation and enhancement characteristics are variable at CT. The typical MRI appearance is a heterogeneous lesion that enhances moderately to avidly and contains bundles of collagen that are hypointense on

T2-weighted images and do not enhance.98 Recurrence is common after surgical resection.

Malignant Chest Wall Masses. More than half of malignant chest wall masses are metastatic lesions or locally invasive breast, lung, or pleural tumors. The chest wall is an uncommon site for metastatic disease, and is usually involved only in the context of widespread metastasis.92,115 The most common primary chest wall malignancies are sarcomas, approximately half of which originate from the soft tissues and half of which are of cartilaginous or bony origin. Sarcomas. Chondrosarcomas are the most common primary chest wall malignancy. These tumors are most often anteriorly located, arising from the costochondral junctions or sternum. Up to 20% arise from the ribs themselves. In about 10% of cases, chondrosarcoma is due to malignant transformation of a benign lesion such as enchondroma. Typically, chondrosarcomas are irregularly shaped, with bone destruction and variable calciication. Chondroid mineralization in a ring-and-arc coniguration is characteristic and best demonstrated by CT. On MRI, chondrosarcomas are lobulated heterogeneously enhancing masses that are isointense to muscle on T1-weighted sequences and iso- or hyperintense relative to fat on T2-weighted images. Osteosarcomas are rare in the thorax and are most often found in the ribs, scapula, and clavicle in young adult patients. Metastatic involvement of the lungs and lymph nodes is more common with chest wall osteosarcoma than with peripheral osteosarcoma. On CT there is varied calciication that is greatest centrally and decreases toward the periphery. T1-weighted images show the lesion to be hyperintense relative to muscle, and T2-weighted images demonstrate high signal intensity. Enhancement is heterogeneous. Liposarcomas are classiied by the World Health Organization into ive groups based on histologic composition: well-differentiated (most common), dedifferentiated, myxoid, pleomorphic, and mixed. Approximately 50% to 75% of a typical well-differentiated liposarcoma is fat. Features that favor well-differentiated liposarcoma over lipoma on MRI include septa greater than 2 mm thick and nodular nonadipose components; however, in 4% to 9% of cases, well-differentiated

CHAPTER 39

Disease of the Pleura, Chest Wall, and Diaphragm

A

C

B

D

1131

FIG 39-44 Chest PA (A) and lateral (B) radiographs and CT scans (C and D) in a patient with a left upper chest wall Askin’s tumor.

liposarcoma and lipoma may be indistinguishable. Other histologic types of liposarcoma contain less fat (usually 1).42 This inding is frequently associated with airway malacia (excessive expiratory collapsibility of the airway lumen) (see Fig. 40-5B). The tracheal wall is composed of several layers, including an inner mucosa layer, submucosa, cartilage or muscle, and an outer adventitial layer.73 On axial CT images, the tracheal wall is usually visible as a 1- to 3-mm soft tissue density stripe, demarcated internally by the air-illed tracheal lumen and externally by the adjacent fat density of the mediastinum73 (Fig. 40-6). The posterior wall is typically thinner than the anterior and lateral walls. Cartilage within the tracheal wall may normally appear slightly denser than surrounding soft tissue and fat.73 Calciication of cartilage may be observed in older patients, especially women.73 Calciied thickening of the tracheal wall is also associated with tracheal pathology, particularly relapsing polychondritis. Thickening of the airway wall (with or without calciication) is an important sign of tracheal pathology (Fig. 40-7). Axial images are the reference standard for assessing tracheal wall thickening, a inding that may be overlooked at conventional bronchoscopy and threedimensional (3D) reconstruction images. The distribution of wall thickening can be helpful in limiting the differential diagnosis of the various causes of tracheal stenosis. For example, disorders of cartilage (e.g., relapsing polychondritis [see Fig. 40-7], tracheobronchopathia osteochondroplastica) will spare the posterior membranous wall of the trachea, whereas other disorders generally result in circumferential thickening (Fig. 40-8). The main bronchi arise from the trachea at the level of the carina and course obliquely to the axial plane. Owing to the limitations of axial images for assessing structures that course obliquely, multiplanar and 3D reconstruction images are particularly helpful for evaluating caliber changes in the mainstem bronchi.

Lobar, Segmental, and Subsegmental Bronchi Similar to the pulmonary vasculature, the airways divide by dichotomous branching, with roughly 23 generations of branches between the trachea and alveoli.51 Bronchial walls are composed of both cartilaginous and ibromuscular elements. For bronchi with luminal diameters less than 5 mm, the bronchial wall typically measures between one sixth and one tenth of the airway lumen.51 Thus because identiication of a bronchus on CT depends on visualization of the thin airway wall, typically only the irst eight generations of bronchi can be visualized with thin-section high-resolution CT (HRCT) techniques. As a general

CHAPTER 40

Airway

1139

A

FIG 40-3 Normal trachea. Minimum intensity projection, sagittal oblique reformation CT image of the normal trachea (arrow) shows the typical angled course of the trachea from a proximal anterior location to a midcoronal position at the level of the carina.

B FIG 40-1 Normal tracheal dynamics. End-inspiratory image (A) shows a round coniguration of the tracheal lumen. At end-expiration (B), the tracheal lumen has narrowed slightly, with lattening of the posterior membranous wall (arrow).

FIG 40-4 Saber sheath trachea. Axial CT image demonstrates an elongated sagittal dimension of the trachea with relative narrowing coronally, consistent with a saber sheath coniguration.

FIG 40-2 Normal trachea. Minimum intensity projection, coronal oblique reformation CT image of the normal trachea and bronchi. Main bronchi originate from the inferior trachea at the level of the carina (arrow).

rule the limit of visibility of normal bronchi on CT is generally a 2-mm-diameter bronchus that is typically located about 2 cm from the pleural surface.51 On CT the appearance of bronchi depends on their course with respect to the axial plane. For example, bronchi that course horizontally within the axial plane (e.g., right and left upper lobe bronchi and anterior upper lobe segmental bronchi; superior segment lower lobe bronchi) will be viewed along their long axes (Fig. 40-9), whereas those that course perpendicularly (e.g., bronchus intermedius, lower lobe bronchi and basilar segments, upper lobe apical and apical-posterior segments) will be viewed as small circular lucencies18 (Fig. 40-10). Bronchi that course obliquely to the axial plane are more dificult to evaluate with CT than other bronchi are. On axial images, they are typically seen as oval lucencies that can be connected by scrolling a series of axial slices. These bronchi include the distal right middle lobe bronchus and its medial and lateral segmental branches (Fig. 40-11)

1140

PART II CT and MR Imaging of the Whole Body

A

B FIG 40-5 Lunate trachea. Axial end-inspiratory CT image (A) shows an elongated coronal dimension of the trachea. Axial dynamic expiratory CT image (B) shows severe malacia with complete collapse of the tracheal lumen (arrow).

FIG 40-6 Normal trachea. Axial CT image shows normal thickness of the tracheal wall. Note the paper-thin quality of the posterior membranous wall (white arrow) and the slightly thicker anterior and lateral walls (black arrows).

FIG 40-8 Postintubation stenosis. Axial CT image shows circumferential wall thickening of the subglottic airway lumen.

and the lingular bronchus and its superior and inferior segmental divisions. Bronchi and pulmonary arteries have a parallel course, and the bronchial lumen is generally about the same diameter as the lumen of its accompanying pulmonary artery. This relationship can be helpful for identifying bronchiectasis, a term that refers to irreversible dilation of a bronchus. When a bronchus is dilated, its lumen appears larger than that of the accompanying pulmonary artery. When viewed in cross section, this mimics the appearance of a signet ring (the “signet ring sign”) (Fig. 40-12). Identiication of a dilated bronchus that courses horizontally is usually based on a lack of normal tapering of the bronchus as it courses from proximal to distal. Subsegmental bronchi show considerable variability in their branching patterns, and there is currently no widely accepted nomenclature for their description.51 FIG 40-7 Relapsing polychondritis. Axial CT image shows thickening of the anterolateral tracheal walls, with focal calciication (arrow). Note the characteristic sparing of the posterior membranous wall.

Bronchioles Bronchioles are small airways that do not contain cartilage and glands.18 They are composed of membranous (lobular and terminal)

CHAPTER 40

A

Airway

1141

B FIG 40-9 CT appearance of bronchi that course horizontally within the axial plane. A, Axial CT image shows the right upper lobe bronchus (arrow). B, Axial CT image shows the superior segment right lower lobe bronchus (arrow).

A

B FIG 40-10 CT appearance of bronchi that course perpendicularly to the axial plane. A, Axial CT image shows bronchus intermedius (arrow). B, Axial CT image shows lower lobe segmental bronchi (arrows).

FIG 40-11 CT appearance of bronchi that course obliquely to the axial plane. Axial CT image shows the origin of the right middle lobe medial and lateral segmental bronchi (arrows).

FIG 40-12 Signet ring sign. The lumen of the dilated bronchus (arrow) is larger than its accompanying pulmonary artery, mimicking a signet ring.

1142

PART II CT and MR Imaging of the Whole Body

A

B FIG 40-13 Subglottic stenosis. A, Axial CT image shows subtle asymmetric wall thickening (arrow) that could easily be overlooked or underestimated. B, Minimum intensity projection multiplanar reformation image of the trachea shows moderate tracheal stenosis (arrows).

bronchioles and respiratory bronchioles. Because of their small size (internal diameter ≤ 2 mm), normal bronchioles are below the resolution of HRCT. However, in the setting of bronchiolar disease, both direct and indirect signs of disease may be visualized on HRCT. Terminal bronchioles and their accompanying centrilobular pulmonary arterial branches are located in the center of the secondary pulmonary lobule.18 This location accounts for the characteristic centrilobular distribution of bronchiolar abnormalities on CT, which are reviewed further in the inal section of this chapter.

IMAGING TECHNIQUES With the latest generation of multidetector-row CT (MDCT) scanners, thin-section images of the entire central airways can be obtained in only a few seconds, creating an isotropic data set in which the resolution is the same in the axial, coronal, and sagittal planes. Compared to standard helical CT scanners, MDCT provides higher spatial resolution, faster speed, greater anatomic coverage, and higher-quality multiplanar reformation and 3D reconstruction images. Together, these features have combined to revolutionize CT imaging of the airways. Axial CT images provide anatomic information regarding the airway lumen, airway wall, and adjacent mediastinal and lung structures. Although axial CT images are considered the reference standard for airway imaging, it is important to be aware of the limitations of the axial plane for assessing the larger airways, including limited ability to detect subtle airway stenoses, underestimation of the craniocaudal extent of disease, dificulty displaying complex 3D relationships of the airway, and inadequate representation of airways oriented obliquely to the axial plane.9,11,49,59,60,62,64 These limitations have important implications for the assessment of certain airway disorders such as airway stenoses and complex congenital airway abnormalities. Multiplanar and 3D reconstruction images help overcome these limitations by providing a more anatomically meaningful display of complex structures

such as the airways.9,11,49,59,60,62,64 These images have been shown to enhance detection of airway stenoses (Fig. 40-13), aid assessment of the craniocaudal extent of stenoses, and clarify complex congenital airway abnormalities.54 They have also been shown to improve diagnostic conidence of interpretation, enhance preprocedural planning for bronchoscopy and surgery, and improve communication among radiologists, clinicians, and patients.9,11,64 For detection of bronchial and bronchiolar diseases, thin-section (1-1.5 mm) HRCT images should be obtained. Although this technique has traditionally been performed by obtaining noncontiguous images acquired at intervals of 1 or 2 cm, MDCT allows for a volumetric spiral acquisition with retrospective reconstruction of both thinsection and thick-section data sets. Such volumetric acquisition offers several advantages, including the enhanced ability to detect bronchiectasis44 (Fig. 40-14) and the possibility of reconstructing multiplanar or postprocessed images to facilitate detection and characterization of airway-related abnormalities. For example, it has been shown that contiguous 3-mm-collimation CT images are superior to noncontiguous HRCT images for detection of bronchiectasis (Fig. 40-15) and have signiicantly better interobserver agreement for the presence and extent of bronchiectasis.44 Anatomic imaging of the airways is performed at end-inspiration. However, several airways diseases, including tracheobronchomalacia (see Fig. 40-5B) and constrictive bronchiolar diseases, will be either undetected or underestimated if only end-inspiratory imaging is performed. Thus expiratory imaging should be performed as a complement to end-inspiratory imaging for suspected airway malacia and bronchiolar disorders. Additionally, expiratory imaging facilitates a comprehensive assessment of diffuse lung diseases that have an obstructive airways component, such as hypersensitivity pneumonitis (Fig. 40-16) and sarcoid. A variety of expiratory methods are available. For assessment of tracheomalacia, dynamic expiratory imaging (imaging during a forced expiration) has been shown to be superior to end-expiratory imaging

CHAPTER 40 (imaging after exhalation).4 However, end-expiratory imaging is typically the standard technique for evaluating air trapping in the lung parenchyma, an indirect sign of constrictive bronchiolar disease. Similar to end-inspiratory HRCT imaging, end-expiratory HRCT was traditionally performed at selected noncontiguous levels. More recently, however, advances in CT technology have allowed for volumetric end-expiratory HRCT imaging.53 This method has potential

Airway

1143

advantages over noncontiguous axial HRCT in terms of enhanced visualization of the airways conducting to regions of air trapping and in the ability to create multiplanar reformation images, which have the potential to enhance the clarity of borders of air trapping compared to axial images.53 Although end-expiratory imaging is routinely applied to detect air trapping, other methods of expiratory imaging have also been reported.15,23,43 For example, free breathing methods and lateral decubitus positioning have been reported for evaluating pediatric patients who may not be able to cooperate with standard end-expiratory breathing maneuvers.

PATHOLOGY Tracheobronchial Stenosis

FIG 40-14 Bronchiectasis. Coronal reformation image demonstrates bronchiectasis and bronchial wall thickening in the left lower lobe. Coronal images enhance the continuous display of bronchi that course perpendicularly to the axial plane.

A

Tracheobronchial stenosis is deined as focal or diffuse narrowing of the tracheal lumen and may occur secondary to a wide variety of benign and malignant causes (Box 40-1). In the following paragraphs, imaging methods and a general approach to recognition and characterization of tracheobronchial stenoses are reviewed. Axial CT images provide exquisite anatomic display of the tracheal wall, tracheal lumen, and adjacent mediastinal and lung structures. Use of narrow collimation (≤3 mm) enhances the ability to detect and characterize tracheal wall thickening (deined as wall thickness > 3 mm) and calciication. However, axial images have a limited ability to detect subtle airway stenoses and frequently underestimate the craniocaudal extent of stenoses.9,11,49,58,60,64,69 By providing a continuous anatomic display of the airways, multiplanar and 3D reconstruction images help overcome these limitations.11 In settings where such reconstructions are not possible, careful review of contiguous thin-section axial images can help prevent the radiologist from overlooking stenoses. Use of thin-section images is particularly advantageous in the subglottic region, where stenoses are often focal and may be easily overlooked or underestimated on 5-mm sections (see Fig. 40-13). CT evaluation of suspected tracheal stenosis is routinely performed at end-inspiration during a single breath hold. An additional sequence during dynamic expiration may be helpful to assess for

B FIG 40-15 Enhanced detection of bronchiectasis with helical CT. A, Axial, prone, noncontiguous highresolution CT image demonstrates a small cystic space (arrow) in the right middle lobe with no discernible connection to the airway. B, Axial helical CT image identiies the connecting airway (arrow), allowing for a conident diagnosis of bronchiectasis.

1144

PART II CT and MR Imaging of the Whole Body

A

B FIG 40-16 Hypersensitivity pneumonitis. A, Axial end-inspiratory CT image demonstrates mosaic lung attenuation with diffuse areas of ground-glass attenuation and a subtle focus (arrow) of reduced lung attenuation. B, Axial end-expiratory CT image demonstrates multiple foci of lobular air trapping (arrows) consistent with small airways disease.

BOX 40-1

Causes of Tracheobronchial

Stenosis Iatrogenic Post intubation* Lung transplantation Idiopathic Infection Laryngotracheal papillomatosis† Rhinoscleroma Tuberculosis Neoplasm Primary tracheal neoplasm (squamous carcinoma, adenoid cystic carcinoma) Direct invasion (lung, esophagus, thyroid) Secondary neoplasm (breast, renal, melanoma, thyroid) Saber sheath deformity Systemic diseases Amyloidosis Inlammatory bowel disease Relapsing polychondritis Sarcoidosis Wegener’s granulomatosis Tracheobronchopathia osteochondroplastica Trauma *Most common etiology. † Although papillomas represent growth of new tissue, laryngotracheal papillomatosis is most frequently categorized as a nonneoplastic disease.

tracheomalacia, which may coexist with tracheobronchial stenoses, especially among patients with relapsing polychondritis, postintubation stenosis, and airway narrowing secondary to long-standing extrinsic compression (e.g., thyroid enlargement or mediastinal aortic vascular anomalies).8,13 It is important to accurately assess the location, length, and distribution of the stenosis as well as the presence, distribution, and type of

FIG 40-17 Amyloidosis. Axial CT image shows marked thickening of anterolateral tracheal walls (arrow) with foci of calciication. Note sparing of the posterior membranous wall. An identical appearance can be seen in relapsing polychondritis.

wall thickening. Consideration of these factors in combination with ancillary thoracic indings and pertinent clinical and laboratory data will allow the radiologist to effectively narrow the broad differential diagnosis of tracheobronchial stenosis to a few likely entities. In certain cases, such as relapsing polychondritis or tracheobronchopathia osteochondroplastica, a conident diagnosis can be made on the basis of imaging indings alone. As reviewed earlier in this chapter, the posterior membranous wall of the trachea is devoid of cartilage. Thus diseases such as relapsing polychondritis (see Fig. 40-7) or tracheobronchopathia osteochondroplastica—which target the cartilage—will characteristically spare the posterior tracheal wall,57,73 whereas most other causes of stenosis will result in circumferential tracheal wall involvement (see Fig. 40-13). Interestingly, amyloidosis may result in circumferential thickening or may spare the posterior wall (Fig. 40-17).

CHAPTER 40 BOX 40-2

Differentiating Features of Tracheobronchial Stenosis

BOX 40-3

Sparing of Posterior Membranous Wall Relapsing polychondritis Tracheobronchopathia osteochondroplastica ± Amyloidosis (may also be circumferential)

Malignant Neoplasms Epithelial Squamous cell carcinoma Adenoid cystic carcinoma Carcinoid Mucoepidermoid carcinoma Adenocarcinoma Small cell undifferentiated carcinoma Large cell carcinoma Acinic cell carcinoma Malignant salivary gland–type mixed tumors Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements

“Hourglass” Coniguration Post intubation Calciication Amyloid Relapsing polychondritis Tracheobronchopathia osteochondroplastica Tuberculosis Tracheomalacia (Coexisting with Stenosis) Post intubation Relapsing polychondritis Saber sheath trachea Long-standing extrinsic compression

Although there is signiicant overlap in the imaging features of many causes of tracheobronchial stenosis, several key imaging features can help to effectively narrow this broad differential diagnosis. As listed in Box 40-2, these features include sparing of the posterior membranous wall, hourglass coniguration, calciication, and coexisting tracheomalacia. Additionally, systemic disorders (e.g., amyloid, inlammatory bowel disease, polychondritis, sarcoid, tuberculosis, Wegener’s granulomatosis) are often associated with characteristic ancillary imaging and laboratory indings that may suggest their diagnosis. Postintubation stenosis is by far the most common cause of acquired tracheal stenosis.19 It typically occurs secondary to injury of the trachea from the high pressure of an endotracheal tube balloon against the wall of the trachea.19,57 This initially results in mucosal necrosis, followed by scarring and stenosis.19,57 A study comparing MDCT with the gold standard of bronchoscopy showed a high sensitivity (92%) and speciicity (100%) for detection of postintubation stenosis.68 The most common CT inding in postintubation stenosis is a focal area of proximal tracheal luminal narrowing measuring approximately 2 cm in craniocaudal length19,57,73 (see Fig. 40-13). The focal nature and circumferential narrowing may produce a characteristic hourglass coniguration. Less common indings include a thin membrane projecting into the tracheal lumen or a long segment of eccentric soft tissue thickening.19,57

Tracheobronchial Neoplasms Tracheobronchial neoplasms are rare; it has been estimated that a primary tracheal tumor is roughly 180 times less common than a primary lung cancer.31 A neoplasm within the central airways is more likely due to direct airway invasion by an adjacent secondary neoplasm originating from the thyroid, lung, or esophagus.16 The majority of primary tracheal neoplasms in adults are malignant.19,46 Although the differential diagnosis of central airway neoplasms is broad (Box 40-3), only ive histologies comprise the majority of primary tracheobronchial tumors: squamous cell carcinoma, adenoid cystic carcinoma (Fig. 40-18), carcinoid, mucoepidermoid carcinoma, and squamous cell papilloma.22 The most common cell

Airway

1145

Malignant and Benign Tracheobronchial Neoplasms

Mesenchymal Fibrosarcoma Rhabdomyosarcoma Angiosarcoma Kaposi’s sarcoma Liposarcoma Osteosarcoma Leiomyosarcoma Chondrosarcoma Paraganglioma Spindle cell sarcoma Lymphoma Malignant ibrous histiocytoma

Benign Neoplasms Epithelial Squamous cell papilloma Papillomatosis Pleomorphic adenoma Glandular papilloma Adenomas of salivary gland type Mucous gland adenoma Monomorphic adenoma Oncocytoma Mesenchymal Hamartoma Neuroibroma Chondroma Fibroma Hemangioma Granular cell tumor Schwannoma Fibrous histiocytoma Pseudosarcoma Hemangioendothelioma Leiomyoma Chondroblastoma Lipoma Glomus tumor

type is squamous cell carcinoma, which is associated with cigarette smoking.19,46 The second most common cell type is adenoid cystic carcinoma, which is not smoking related.19,46 It has a better prognosis than squamous cell carcinoma, but late recurrence is relatively common. The most common benign tracheal neoplasm is squamous cell papilloma, which is also associated with cigarette smoking.19,46 Carcinoid tumors are neuroendocrine neoplasms that most commonly arise within the mainstem and lobar bronchi, but about 15% develop within the segmental bronchi or lung periphery.54,56 They are not associated with cigarette smoking. MDCT is the imaging modality of choice for detection and staging of central airway neoplasms. Multiplanar reformation and 3D reconstruction images complement conventional axial images by providing a more anatomically meaningful display of the neoplasm and its relationship to adjacent structures, and by accurately determining the craniocaudad extent of disease.11 Virtual bronchoscopy images provide a unique intraluminal perspective of the tumor and adjacent proximal and distal airways (see Fig. 40-18), which may not be accessible with conventional bronchoscopy in cases in which there is high-grade luminal narrowing or obstruction. Moreover, this method can provide a more global perspective of an endoluminal lesion than conventional bronchoscopy can. Thus it provides complementary information to conventional bronchoscopy. MDCT provides important information for preprocedural planning. If they are resectable, surgery is the optimal therapy for both benign and malignant airway neoplasms.31 Radiation therapy may be

1146

PART II CT and MR Imaging of the Whole Body

A

B FIG 40-18 Adenoid cystic carcinoma. A, Axial CT scan shows a lobulated intraluminal mass (black arrow) at the level of the carina. An adjacent tubular structure represents a normal partially opaciied azygos vein (white arrow). B, Virtual bronchoscopic image provides an intraluminal perspective of the mass (arrows).

FIG 40-19 Right lower lobe atelectasis (arrow) secondary to obstructing carcinoid tumor. The obstructing lesion is shown in Figure 40-20.

administered to patients with unresectable disease or as an adjunct to surgery, particularly in patients with adenoid cystic carcinoma.35 MDCT can determine whether a tumor is amenable to complete surgical resection, as well as the approach, type, and extent of surgical resection. MDCT provides critical information for the surgeon, including precise delineation of the 3D size of the neoplasm (e.g., craniocaudal length) and its relationship with other vital (e.g., vascular) structures. MDCT accurately deines the intraluminal and extraluminal extension of tumor, as well as postobstructive complications such as atelectasis (Fig. 40-19), pneumonia, and mucus plugging. Although MDCT can reliably detect the presence of lymphadenopathy, it cannot distinguish between hyperplastic and malignant nodes (Fig. 40-20). Hyperplastic nodes are frequently seen in the setting of postobstructive pneumonitis from an endoluminal neoplasm. Additionally, MDCT does not reliably detect microscopic mediastinal invasion or neural

FIG 40-20 Benign hyperplastic lymph nodes. Coronal oblique MIP image shows an enhancing right hilar mass (white arrow) with obstruction of the bronchus intermedius and distal right lower lobe collapse. Enlarged subcarinal lymph nodes (black arrow) proved to be benign hyperplastic nodes at biopsy.

invasion.37 MDCT may detect pulmonary and extrapulmonary metastases, thereby enhancing tumor staging. Finally, for patients who are not surgical candidates, MDCT can evaluate patency of the airways distal to the neoplasm, thereby determining suitability of the airways for palliative stent placement. When a discrete tracheal mass is identiied on imaging studies, the diagnosis of a primary tracheal neoplasm can usually be made with a

CHAPTER 40 high degree of conidence. CT can frequently suggest whether a tracheal lesion is malignant or benign.35 Although some overlap exists, benign lesions are typically less than 2 cm in diameter, with welldeined smooth borders and without evidence of contiguous tracheal thickening or mediastinal invasion. In contrast, malignant lesions usually vary in size between 2 and 4 cm in diameter, with a lat or polypoid shape and irregular or lobulated borders. Contiguous tracheal wall thickening and mediastinal invasion are frequently observed. Although CT usually cannot distinguish between neoplastic cell types, detection of fat within a lesion on CT is nearly pathognomonic for a hamartoma or lipoma, and identiication of calciication within a lesion is highly suggestive of a chondroid tumor (chondroma, chondrosarcoma). Vigorous enhancement of a bronchial neoplasm is typical of a carcinoid tumor. In a minority of cases, tracheal neoplasms will present as eccentric or circumferential tracheal wall thickening rather than as a discrete mass (Fig. 40-21). In such cases the differential diagnosis includes tracheal stenosis from a variety of nonmalignant entities. In general the presence of marked irregularity of tracheal wall thickening and the presence of extratracheal extension favor a primary tracheal neoplasm, but biopsy is usually necessary to establish the diagnosis.

Airway

1147

Although bronchoscopy with functional maneuvers can reliably detect tracheobronchomalacia, it is not clinically feasible or desirable to perform this invasive test in all patients who present with chronic cough and other nonspeciic respiratory symptoms. Fortunately, recent advances in MDCT afford the opportunity to noninvasively diagnose tracheobronchomalacia with sensitivity that is similar to that of conventional bronchoscopy.22,40,76 Changes in size of malacic trachea and bronchi depend on the difference between the intraluminal pressure inside the airways and the pleural (intrathoracic) pressure outside.4,13 Pleural pressure depends mostly on respiratory muscles and is high during expiratory efforts. In contrast, intraluminal pressures are highly variable and depend on airlow. When airlow is zero, intraluminal pressure equals alveolar

Tracheobronchomalacia Tracheobronchomalacia refers to weakness of the airway walls and/or supporting cartilage and is characterized by excessive expiratory collapse8,13,29,33,34 (Fig. 40-22; see Fig. 40-5). Although irst reported in the 1930s and 1940s, this condition has only recently been recognized as a relatively common and potentially treatable cause of chronic cough, dyspnea, and recurrent infections.13 Tracheobronchomalacia may be either congenital or acquired. The acquired form is associated with a variety of risk factors and comorbidities, most notably chronic obstructive pulmonary disease8,13,33 (Box 40-4). Because it cannot be detected with routine end-inspiratory imaging studies, tracheobronchomalacia is widely considered an underdiagnosed condition; bronchoscopic series report a prevalence ranging from 4.5% to 23%.32,33,55 Recent CT studies also support the concept that this is an underdiagnosed condition,28,39 with a prevalence of 10% in a recent CT angiography study of patients with nonspeciic respiratory symptoms referred for suspected pulmonary embolism.28

A

FIG 40-21 Adenoid cystic carcinoma. Axial CT image demonstrates eccentric circumferential wall thickening in subglottic airway (arrows).

B FIG 40-22 Tracheomalacia in patient with relapsing polychondritis. End-inspiratory image (A) of proximal trachea shows partially calciied anterolateral wall thickening; at dynamic-expiration (B), there is marked malacia (arrow). (The end-inspiratory image is shown in a soft tissue window setting to enhance display of wall thickening.)

1148

PART II CT and MR Imaging of the Whole Body

Risk Factors for Acquired Tracheomalacia BOX 40-4

Chronic obstructive lung disease Posttraumatic and iatrogenic factors Post intubation Post tracheostomy Radiation therapy External chest trauma Post lung transplantation Chronic infection/bronchitis Chronic inlammation Relapsing polychondritis Chronic external compression of the trachea Paratracheal neoplasms (benign and malignant) Paratracheal masses (e.g., goiter, congenital cyst) Aortic aneurysms and vascular rings Skeletal abnormalities (e.g., pectus, scoliosis) FIG 40-23 Frown sign. Expiratory CT image demonstrates frownlike

pressure and differs from pleural pressure only by the elastic recoil pressure of the lung, which depends on lung volume. At maximal lung volume with no low (end-inspiration), the intraluminal pressure is 20 to 30 cm H2O greater than pleural pressure, and the pressure difference expands the trachea. At low lung volumes with no low (endexpiration), the intraluminal pressure is nearly equal to pleural pressure and the trachea is unstressed. The trachea is most compressed during cough and dynamic expiration at low lung volume when pleural pressure is high (≈100 cm H2O) and expiratory low limitation in the small airways prevents transmission of the high alveolar pressures to the central airways. Under these conditions, intraluminal pressure is nearly atmospheric and the large transmural pressure causes tracheal collapse.74 Baroni and colleagues directly compared the ability of endexpiratory and dynamic expiratory CT imaging methods to elicit tracheobronchomalacia.5 Consistent with the principles of respiratory physiology, this study showed that dynamic expiratory CT elicited a signiicantly greater degree of tracheal collapse than end-expiratory CT did. Tracheobronchial collapse is thus ideally measured during forceful exhalation. Historically, a diagnosis of tracheobronchomalacia has been made using a threshold of 50% or more expiratory reduction in the airway lumen when using either bronchoscopy or CT.40 Recently, however, studies of healthy volunteers with normal pulmonary function have reported mean levels of expiratory collapse in the trachea and right and left main bronchi of 54%, 67%, and 61%, respectively.10,41,61 Moreover, in a minority of healthy individuals, the bronchus intermedius may show complete expiratory collapse. Although future studies are necessary to precisely determine a more rigorous threshold for diagnosing tracheobronchomalacia, it is likely that such a threshold will be deined as at least 70% expiratory collapse. In the meantime, to avoid overdiagnosis of this condition, identiication of excessive airway collapse on CT or bronchoscopy should be closely correlated with clinical symptoms, risk factors, and pulmonary function testing.61 Interpretation of CT images for the diagnosis of tracheobronchomalacia requires careful review and comparison of both end-inspiratory and dynamic expiratory images. End-inspiratory images provide important anatomic information about tracheal size and shape, thickness of the tracheal wall, and presence or absence of extrinsic masses compressing the trachea. The tracheal lumen is almost always normal

coniguration of the proximal trachea owing to excessive anterior displacement of the posterior membranous wall that parallels the convex contour of the anterior wall, resulting in a characteristic crescentic lucency (arrow) that mimics a frown.

in appearance on end-inspiration CT in patients with tracheobronchomalacia.6 Several exceptions include patients with relapsing polychondritis, who may demonstrate characteristic wall thickening and calciication that spares the posterior membranous wall of the trachea; patients with lunate tracheal shape (coronal > sagittal dimension), which is frequently associated with tracheomalacia; and patients with extrinsic tracheal compression from adjacent vascular anomalies or thyroid masses, in whom long-standing compression has been complicated by tracheomalacia. The most accurate means for diagnosing malacia on CT is to use an electronic tracing tool to calculate the cross-sectional area of the airway lumen on images at the same anatomic level obtained at inspiration and dynamic expiration.8 Such tools can be found on commercially available PACS (picture archiving and communication system) stations as well as with 3D workstations. Care should be taken to ensure that the same anatomic level is compared between the two sequences by comparing vascular structures and other anatomic landmarks. In the setting of severe malacia in which there is near-complete collapse of the airway lumen during expiration, the diagnosis can be conidently made based on visual analysis of the images (see Fig. 40-5B). Interestingly, about half of patients with acquired tracheomalacia will demonstrate an expiratory “frownlike” coniguration, in which the posterior membranous wall is excessively bowed forward and parallels the convex contour of the anterior wall, with less than 6 mm distance between the anterior and posterior walls6 (Fig. 40-23). This appearance, which has been termed the frown sign, is highly suggestive of tracheomalacia and has the potential to aid detection of tracheomalacia when patients inadvertently breathe during routine CT scans.6 Ideally, however, the diagnosis of tracheomalacia should be conirmed and quantiied by a dedicated CT trachea study. When interpreting CT scans of patients with tracheomalacia, it is important to report the severity, distribution, and morphology. These factors have an important impact on treatment decisions, which are based on a combination of symptoms, severity and distribution of disease, and underlying cause of tracheomalacia.48 Patients with severely symptomatic diffuse tracheomalacia characterized by

CHAPTER 40 excessive mobility and weakening of the posterior membranous wall may beneit from tracheoplasty, a surgical procedure that reinforces the posterior wall of the trachea with a Marlex graft.4

Congenital Anomalies A variety of congenital anomalies may affect the trachea and bronchi, including branching anomalies (displaced and supernumerary bronchi), bronchial agenesis and atresia, congenital stenosis, congenital malacia, congenital tracheobronchomegaly, and congenital diverticula.

Displaced Bronchi. Tracheal bronchus refers to an anomalous bronchial origin from the trachea, carina, or main bronchi, usually located within 2 cm of the carina.10,21,51 Most commonly this occurs as a displaced bronchus arising from the lower trachea and supplying the right upper lobe apical segment (Fig. 40-24). Less commonly the entire right upper lobe bronchus may be displaced, a coniguration that is also referred to as a “pig” bronchus. Although usually an asymptomatic and incidentally detected inding, impaired drainage may result in recurrent infections in some cases. Additionally, following endotracheal intubation, atelectasis may occur in the portion of lung supplied by the aberrant bronchus, owing to inadvertent obstruction by the balloon cuff. Other types of displaced bronchi include proximal or distal displacement of segmental or subsegmental bronchi in the same lobe, bridging bronchus (the displaced bronchus arises from the left main bronchus and crosses the midline to supply the right lower lobe), and esophageal bronchus (the displaced bronchus arises from the esophagus and is directed to a lower lobe).21,51,77

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Bronchial Agenesis. Bronchial agenesis occurs in the setting of congenital absence of a lung (pulmonary agenesis), including its vascular and bronchial supply.21,77 This condition has a high mortality rate because of other associated cardiopulmonary abnormalities. It usually presents in neonates with respiratory symptoms, but it can rarely be an incidental inding in older children and adults. The radiographic appearance simulates pneumonectomy, with opaciication of the hemithorax and ipsilateral mediastinal shift. CT conirms unilateral absence of a lung, its bronchi, and vascular supply and may also detect associated congenital heart disease and spinal anomalies.

Bronchial Atresia. Bronchial atresia refers to atresia or obstruction of a segmental or subsegmental bronchus, with normal development of the distal airway.21,77 Typically mucus accumulates within the patent bronchus distal to the atretic segment and the lung hyperinlates beyond the obstruction (Fig. 40-25), most commonly in the apicoposterior segmental bronchus of the left upper lobe. CT indings include a central masslike opacity with a tubular coniguration. The distal segmental branches are dilated and contain secretions. The peripheral lung is hyperexpanded, with decreased attenuation and reduced vasculature. This condition is usually asymptomatic and requires no treatment. Surgery may be indicated for cases complicated by recurrent infections.

Congenital Tracheal Stenosis. Congenital tracheal stenosis is a rare disorder characterized by complete tracheal rings associated with absent or deicient tracheal membranes.2,7,15 It ranges in length from short- to long-segment stenosis. It typically presents during the irst year of life and is associated with a high mortality rate. Symptoms

Supernumerary Bronchi. Cardiac bronchus refers to a supernumerary bronchus arising from the medial wall of the bronchus intermedius.21,47,51,77 This may be a blind ending or may course 1 to 5 cm caudad toward the heart. It may ventilate a hypoplastic lobule and can be associated with a discrete soft tissue mass due to vascularized bronchial or vestigial parenchymal tissue. Although usually asymptomatic, affected patients may present with infection or hemoptysis. Surgical excision is recommended for symptomatic patients.

FIG 40-24 Tracheal “pig” bronchus. Axial CT image shows the anoma-

FIG 40-25 Bronchial atresia. Coned-down view of the left lung from

lous origin of the entire right upper lobe bronchus (arrow) from the lower trachea.

an axial CT image demonstrates a central tubular structure (arrow) with hyperlucency of the apicoposterior segment of the left upper lobe.

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FIG 40-26 Congenital tracheal stenosis. A 3D external rendering of the trachea demonstrates a short-segment stenosis of the lower trachea (arrow).

FIG 40-27 Congenital tracheobronchomegaly. Axial CT image shows massive enlargement of main bronchi and a small bronchial diverticulum (black arrow). Also note mild bronchiectasis (white arrows).

include stridor, wheezing, cyanosis, and recurrent pneumonia. Adult presentation is rare but is more common with short-segment stenosis7 (Fig. 40-26). CT is highly sensitive for evaluating the length and extent of narrowing, as well as for identifying associated cardiopulmonary anomalies, including pulmonary artery sling. On axial CT images there is narrowing of the tracheal lumen, with an O-shaped coniguration and absence of airway wall thickening. Virtual bronchoscopy is diagnostic by showing concentric rings extending along the posterior wall of the trachea. Surgical treatment usually involves resection of the involved segment or a slide tracheoplasty.7 Asymptomatic pediatric patients may be followed by CT to noninvasively monitor tracheal growth.63

Congenital Tracheomalacia. Congenital tracheomalacia refers to

FIG 40-28 Tracheal diverticulum. Axial CT image demonstrates a small

softening of the trachea secondary to weakening or deiciency of cartilage, resulting in increased tracheal compliance with excessive expiratory collapse.13 This condition is most commonly identiied in premature infants, likely related to inadequate maturation of the tracheobronchial cartilage. It may also be associated with diseases involving cartilage (e.g., polychondritis, chondromalacia, Hunter’s and Hurler’s syndromes).13 Symptoms include expiratory stridor and a barking cough. Intervention is unnecessary in most cases because tracheal cartilage strengthens and stiffens as the child grows. Patients who do not spontaneously improve may respond to continuous positive airway pressure or surgical intervention (e.g., aortopexy or tracheoplasty).

single or multiple invaginations of the tracheal wall. They commonly arise 4 to 5 cm below vocal cords or 2 to 3 cm above the carina on the right lateral aspect of the trachea (Fig. 40-28). In the absence of symptoms, no treatment is necessary.

Congenital Tracheomegaly. Congenital tracheomegaly is also referred to as Mounier-Kuhn syndrome and is characterized by dilation of the trachea and main bronchi owing to severe atrophy of longitudinal elastic ibers and thinning of the muscularis mucosa.65,75 Affected patients typically present during the third and fourth decades with recurrent respiratory infections. On imaging studies there is dilation of the tracheobronchial lumen, often associated with a corrugated appearance of the tracheal wall and frequent diverticula (Fig. 40-27). Tracheobronchomalacia is commonly identiied at expiratory imaging.

Congenital Tracheal Diverticula. Congenital tracheal diverticula are less common than the acquired form.66 They are characterized by

diverticulum (arrow) arising from the junction of the right lateral and posterior tracheal walls.

Bronchiectasis Bronchiectasis, deined as irreversible dilation of the bronchi, may occur secondary to a wide variety of congenital and acquired causes25,36,50 (Box 40-5). Infection is the most common cause.50 Affected patients may present with chronic cough, expectoration of purulent sputum, recurrent infections, and hemoptysis. The diagnosis is made on CT by identifying dilation of the bronchi, with or without accompanying bronchial wall thickening. Bronchiectasis may be classiied as cylindrical, varicose, or cystic.25,36,50 Diagnostic criteria for cylindrical bronchiectasis include a bronchial diameter greater than its accompanying artery (signet ring sign) (see Fig. 40-12), lack of bronchial tapering (Fig. 40-29), and identiication of a bronchus within 1 cm of the costal pleura or abutting the mediastinal pleura.25,36,50 Varicoid bronchiectasis is characterized by a beaded appearance mimicking a “string of pearls” (Fig. 40-30). Cystic bronchiectasis is characterized by thin-walled cystic

CHAPTER 40 BOX 40-5

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Causes of Bronchiectasis

Acquired bronchial obstruction (neoplasm, foreign body, broncholith) Asthma Extrinsic bronchial obstruction (lymph node enlargement, neoplasm) Idiopathic Immune deiciency (e.g., IgG deiciency, human immunodeiciency virus infection) Immunologic disorders (allergic bronchopulmonary aspergillosis, collagenvascular disorders, inlammatory bowel disease, graft-versus-host disease following stem cell transplant) Infection* (bacteria, mycobacteria, fungus, virus) Inhalational injury (aspiration, toxic gases) Inherited molecular and cellular defects (cystic ibrosis, α1-antitrypsin deiciency) Inherited bronchial structural deiciencies (bronchial atresia, congenital tracheobronchomegaly, Williams-Campbell syndrome) Primary ciliary dyskinesia (Kartagener’s syndrome) Pulmonary ibrosis (results in traction bronchiectasis) *Most common cause.

FIG 40-30 Bronchiectasis. Axial CT image demonstrates a beaded appearance of dilated bronchi (arrow) in the right upper lobe, consistent with varicoid bronchiectasis.

FIG 40-29 Bronchiectasis. Axial CT image shows lack of tapering of left lower lobe bronchi (arrow), with peripheral dilation.

spaces that connect with the proximal airways, with or without luid levels (Figs. 40-31 and 40-32). Although volumetric axial images have a high sensitivity for detection of bronchiectasis, the additional review of coronal multiplanar reformation images has been shown to improve detection rate and diagnostic conidence in determining the distribution and type of bronchiectasis.69 CT has limited ability to determine the cause of bronchiectasis,50 but the distribution of disease can help suggest the most likely causes. For example, a bilateral upper lobe distribution is most commonly observed in cystic ibrosis and allergic bronchopulmonary aspergillosis, a unilateral upper lobe distribution is most common in tuberculosis, and a lower lobe distribution is most common in patients with bronchiectasis secondary to childhood viral infections.14 Right middle lobe and lingular distribution of bronchiectasis is often seen in association with the bronchiectatic form of atypical mycobacterial infection45 (Fig. 40-33). Affected patients are typically elderly white women who present with a chronic cough and CT indings of cylindrical bronchiectasis, centrilobular nodules, and tree-in-bud opacities. Impaction of bronchiectatic airways characteristically results in tubular opacities with a Y- or V-shaped coniguration, often mimicking

FIG 40-31 Bronchiectasis. Axial CT image demonstrates cystic dilation of bronchi, some of which have small air-luid levels (arrow).

a “gloved inger” (Fig. 40-34). Impaction of a single bronchus may mimic a parenchymal mass, but careful inspection typically reveals a tubular rather than round coniguration (Fig. 40-35). For airways coursing perpendicular to the axial plane, scrolling through a series of axial images or assessment with multiplanar reformations can be helpful to avoid misdiagnosis as a parenchymal mass.

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FIG 40-32 Bronchiectasis. Coronal reformation CT image shows multiple foci of cystic bronchiectasis, with a few air-luid levels (arrow). Also note paraseptal emphysema, most marked at the right apex.

FIG 40-34 Allergic bronchopulmonary aspergillosis. Coronal reformation CT image demonstrates impacted bronchi in the left upper lobe (arrow) producing a “gloved inger” appearance.

FIG 40-33 Bronchiectatic form of chronic atypical mycobacterial infection. Axial CT scan shows extensive bronchiectasis, bronchial wall thickening, and centrilobular nodules, most severe in the middle lobe and lingula.

Bronchiolitis As discussed earlier in this chapter, normal bronchioles are below the resolution of HRCT. However, in the setting of bronchiolar disease, both direct and indirect signs of disease may be visualized on HRCT. The pathologic classiication includes two main categories of bronchiolitis: cellular bronchiolitis and constrictive (obliterative) bronchiolitis.1 In the setting of cellular bronchiolitis, one may identify poorly deined centrilobular nodules and/or a combination of linear and nodular branching opacities (tree-in-bud sign). Although these indings are usually well visualized on thin-section CT images, the creation of additional maximum intensity projection (MIP) reconstructions

may be helpful in selected cases to facilitate their recognition1 (Fig. 40-36). The tree-in-bud sign, which relects bronchiolar wall thickening and distention with intraluminal secretions, is most characteristic of an acute or chronic infectious etiology (Box 40-6).52,70 Ancillary indings may provide a clue to the responsible infectious organism.1 For example, the presence of cavitary lesions is highly suggestive of tuberculosis, but it may also be seen in atypical mycobacterial and fungal infections.1 Additionally, the identiication of a chronic tree-in-bud pattern in association with bronchiectasis is suggestive of atypical mycobacterial infection, especially when the airway disease is most severe in the middle lobe and lingula. Common noninfectious etiologies for the tree-in-bud pattern include aspiration bronchiolitis and bronchiolitis associated with chronic bronchial diseases. Neoplasm is a rare cause of this pattern and may result from pulmonary tumor embolism or thrombotic microangiopathy of pulmonary neoplasms.71 The presence of poorly deined ground-glass centrilobular nodules without associated tree-in-bud opacities usually represents peribronchiolar inlammation without intraluminal secretions (see Box 40-6).52 This pattern is commonly seen in the setting of subacute hypersensitivity pneumonitis and respiratory bronchiolitis. Information about a patient’s smoking history may be helpful in making this distinction; the former condition is very uncommon in cigarette smokers, whereas the latter is associated with cigarette smoking. Follicular bronchiolitis may also result in this pattern and should be considered when a patient has a history of collagen vascular disease (e.g., rheumatoid arthritis). In the setting of constrictive bronchiolitis, the indings are more subtle and indirect than those associated with cellular bronchiectasis. On end-inspiratory CT images there may be areas of decreased lung attenuation (mosaic perfusion) due to relex vasoconstriction induced by regional underventilation, with accentuation on end-expiratory CT images due to air trapping52 (Fig. 40-37). Constrictive bronchiolitis may be due to a variety of causes (Box 40-7). Additionally, cellular bronchiolitis may sometimes progress to constrictive bronchiolitis.

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B

A

FIG 40-35 Bronchial impaction. A, Axial CT image shows a tubular structure (arrow) in the superior segment of the right lower lobe with no visible aerated bronchus. B, Axial CT image following expectoration of a large mucus plug shows underlying bronchiectasis (arrow).

BOX 40-6

Causes of Cellular Bronchiolitis

Tree-in-Bud Pattern Acute infectious bronchiolitis (especially viral and mycoplasma) Aspiration bronchiolitis Chronic inlammatory conditions of bronchi (asthma, chronic bronchitis, bronchiectasis) Diffuse panbronchiolitis Neoplasm (rare) Centrilobular Nodules without Tree-in-Bud Pattern Hypersensitivity pneumonitis Respiratory bronchiolitis Follicular bronchiolitis

BOX 40-7

Causes of Constrictive

Bronchiolitis

FIG 40-36 Viral bronchiolitis. MIP CT image of the right lower lung demonstrates diffuse centrilobular nodular and branching opacities with tree-in-bud coniguration.

Prior infection (especially viral) Toxic fume inhalation Connective tissue disorders Drugs Chronic transplant rejection Neuroendocrine cell hyperplasia Inlammatory bowel disease

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A

B

C

D FIG 40-37 Constrictive bronchiolitis. A, Axial end-inspiratory HRCT scan is normal. B, Axial end-expiratory HRCT image shows multiple lobular foci of air trapping (arrows). Coronal end-inspiratory (C) and endexpiratory (D) images provide global illustration of lungs with better appreciation of the extent of air trapping (arrows).

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63. Rutter MJ, Willging JP, Cotton RT: Nonoperative management of complete tracheal rings. Arch Otolaryngol Head Neck Surg 130:450–452, 2004. 64. Salvolini L, Secchi EB, Costarelli L, et al: Clinical applications of 2D and 3D CT imaging of the airways—A review. Eur J Radiol 34:9–25, 2000. 65. Shin MS, Jackson RM, Ho K: Tracheobronchomegaly (Mounier-Kuhn syndrome): CT diagnosis. AJR Am J Roentgenol 150:777–778, 1988. 66. Soto-Hurtado EJ, Penuela-Ruiz L, Rivera-Sanchez I, et al: Tracheal diverticulum: A review of the literature. Lung 184:303–307, 2006. 67. Stern EJ, Graham CM, Webb WR, et al: Normal trachea during forced expiration: Dynamic CT measurements. Radiology 187:27–31, 1993. 68. Sun M, Ernst A, Boiselle PM: MDCT of the central airways: Comparison with bronchoscopy in the evaluation of complications of endotracheal and tracheostomy tubes. J Thorac Imaging 22:136–142, 2007. 69. Sung YM, Yi CA, Yoon YC, et al: Additional coronal images using low-milliamperage multidetector row CT: Effectiveness in the diagnosis of bronchiectasis. J Comput Assist Tomogr 27:490–495, 2003. 70. Trigaux JP, Hermes G, Dubois P, et al: CT of saber-sheath trachea: Correlation with clinical, chest radiographic and functional indings. Acta Radiol 35:247–250, 1994.

71. Verma N, Chung JH, Mohammed TL: Tree-in-bud sign. J Thorac Imaging 27:W27, 2012. 72. Vock P, Spiegel T, Fram EK, et al: CT assessment of the adult intrathoracic cross section of the trachea. JCAT 8:1076–1082, 1984. 73. Webb EM, Elicker BM, Webb WR: Using CT to diagnose nonneoplastic tracheal abnormalities. Appearance of the tracheal wall. AJR Am J Roentgenol 174:1315–1321, 2000. 74. Wilson TA, Rodarte JR, Butler JP: Wave speed and viscous low limitation. In Macklem PT, Mead J, editors: Handbook of physiology, The respiratory system, vol 3. Mechanics of Breathing, Part 1, Bethesda, MD, 1986, The American Physiological Society, pp 55–61. 75. Woodring JH, Smith Howard R, Rehn SR: Congenital tracheobronchomegaly (Mounier-Kuhn) syndrome: A report of 10 cases and review of the literature. J Thorac Imaging 6:1–10, 1991. 76. Zhang J, Hasegawa I, Feller-Kopman D, et al: Dynamic expiratory volumetric CT imaging of the central airways: Comparison of standarddose and low-dose techniques. Acad Radiol 10:719–724, 2003. 77. Zylak CJ, Eyler WR, Spizarny DL, et al: Developmental lung anomalies in the adult: Radiologic-pathologic correlation. Radiographics 22:S25–S43, 2002.

41 Chest Imaging in the Pediatric Patient Maryam Etesami, Apeksha Chaturvedi, and Prabhakar Rajiah

INTRODUCTION Plain ilm radiography is the irst-line imaging modality in the evaluation of pediatric chest disorders. However, computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly being used and are more valuable for further characterization of pediatric chest abnormalities. Multidetector CT (MDCT) is the most important imaging modality and is more sensitive than radiographs. CT has several advantages including high spatial resolution, good temporal resolution (for cardiovascular disorders), wide ield of view (FOV), isotropic resolution, and multiplanar reconstruction (MPR) capabilities, all of which make it an excellent modality for a comprehensive evaluation of pulmonary, airway, mediastinal, cardiovascular, and musculoskeletal abnormalities. Modern scanners can scan in a few seconds because of high z-axis coverage and fast gantry rotation time. This is well suited for children and obviates the need for sedation in the majority of cases. The main disadvantage of CT is ionizing radiation, which is associated with stochastic effects, including cancer. Owing to these radiation risks, CT should only be performed for a deinite clinical indication if no alternative nonradiation imaging options exist. The radiation dose should be kept as low as reasonably achievable (ALARA) using several available dose-reduction strategies such as low tube voltage (80 or 100 kVp), low tube current adapted to body weight/size, automated tube current modulation, iterative reconstruction algorithms, and ilters to reduce overranging effect in spiral acquisitions. The scan should be conined to the area of clinical interest. Because of rapid image acquisition, children older than 3 to 4 years are generally compliant for CT scan, particularly if they are aware and prepared. Small children (2-cm) cyst and sometimes multiple or multiloculated cysts, occasionally with small cysts that merge with the adjacent lung. At microscopic examination, these cysts are lined by ciliated epithelium, and some contain mucigenic epithelium, highlighting the embryologic origin of the lung as a foregut derivative.93 Fetal ultrasound of a large-cyst CPAM (type 1) demonstrates numerous variable-sized anechoic spaces intermixed with echogenic soft tissue. On fetal MRI, large-cyst CPAMs manifest as hyperintense unilocular or multilocular lesions with discrete walls on T2-weighted images.36 Postnatal radiography shows variable density in the region of the mass depending on the luid contents of the cysts and possibly mediastinal shift, depending on the size of the CPAM. In the neonatal period a large-cyst CPAM may be seen as a round soft tissue mass that gradually becomes illed with air, since there is delayed clearance of fetal lung luid from the cysts through the abnormal airway. It may be seen as a solitary well-deined air-illed cyst with thin walls or as multiple cysts of varying size (Fig. 41-1A). Air-luid levels may be identiied. Postnatally, CT is optimal for detailed depiction of the lung

B

C FIG 41-1 Cystic adenomatoid malformation. A, Axial CT shows large cystic spaces illed partially with luid in the medial aspect of the right upper lobe. B, Axial CT shows multiple small cystic lesions in the left lower lobe in type 2 CPAM. C, Coronal CT in same patient shows multiple small cystic lesions in the left lower lobe.

CHAPTER 41 parenchyma and airway, and these lesions are readily detectable as well-deined air-illed spaces.19 On pathology, type 2 CPAM is seen as focal areas of microcystic maldevelopment of the lung parenchyma. On histologic analysis, they consist of closely apposed bronchiole-like structures with variable amounts of intervening lung parenchyma. On fetal ultrasound an echogenic mass with multiple small cysts is seen, whereas on MRI it has a variable T2 appearance that depends on the cystic and solid components. Postnatal radiography may demonstrate a heterogeneous intrapulmonary mass with small air-illed cystic areas.180 Some lesions can be subtle and may not be detected at postnatal radiography. CT may allow better evaluation, demonstrating a heterogeneous mass with small cysts (see Fig. 41-1B and C) and variable surrounding consolidation.19 The differential diagnosis for type 1 and 2 CPAM includes congenital diaphragmatic hernia, pulmonary sequestration, bronchogenic cyst, congenital lobar emphysema, and other bronchopulmonary foregut malformations. A microcystic (predominantly solid-appearing) CPAM (type 3) is homogeneously echogenic on prenatal ultrasound, whereas on T2-weighted MRI it manifests as a homogeneously hyperintense solid mass with normal adjacent lung parenchyma.36 Postnatal CT demonstrates an ill-deined area of increased attenuation.19 CPAMs communicate with the bronchial tree but do not typically have a systemic arterial supply. However, occasionally, systemic arterial supply may be seen, particularly in small-cyst CPAMs, and these lesions are called hybrid lesions since they demonstrate histologic and imaging features of both a CPAM and bronchopulmonary sequestration.29,93 A fastgrowing CPAM may cause mediastinal shift and subsequent development of polyhydramnios and hydrops.2,3 Indicators of a poor prognosis in CPAM include large lesions, bilateral lung involvement, and hydrops.2,9,37,42,167 Quantitative measurements of mass size that help predict development of hydrops and poor outcome include a mass-tothorax ratio of more than 0.56167 or a CPAM volume ratio (i.e., volume of the mass divided by head circumference) greater than 1.6.9 Expectant management is appropriate for the nonhydropic fetus, whereas the survival of fetuses with hydrops improves only with fetal intervention, including aspiration of the cyst, thoracoamniotic shunt, injection of sclerosing agent, or in some cases open fetal surgery.46,117,167 After 32 weeks’ gestation, surgical resection of the mass may be possible while the fetus is maintained on placental circulation, using an ex utero intrapartum treatment (“EXIT”) procedure.9 When fetal distress is not evident, the mortality rate may be as low as 5% or less.37 If not recognized antenatally, CPAMs are usually discovered between the neonatal period and 2 years of age, manifesting as respiratory dificulty or infection. Symptomatic infants who are diagnosed postnatally are treated with surgical resection, which generally consists of lobectomy or segmental resection.9 Surgical intervention for asymptomatic CPAMs remains controversial. Recurrent infection and a questionable small risk of malignancy have been cited as reasons for elective resection.9

Congenital Lobar Emphysema/Overinlation Congenital lobar emphysema (CLE) is characterized by progressive lobar overexpansion, usually associated with compression of the remaining lung. CLE can either be due to a primary intrinsic cartilaginous abnormality with weak/absent bronchial walls or secondary to intrinsic/extrinsic bronchial obstruction (e.g., large pulmonary artery or a bronchogenic cyst). In either case the collapsed airway acts as a one-way valve, resulting in air trapping.19 The term congenital lobar overinlation (CLO) is suggested as a substitute because in this process the alveoli expand but are not destroyed. The most commonly involved lobe is the left upper lobe (42%), followed by the right middle lobe

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(35%) and right upper lobe (20%). Involvement of the lower lobes is uncommon (1%).151 Males are more frequently affected than females. It presents with respiratory symptoms in the neonatal period but can also be detected incidentally on fetal ultrasound as a homogeneously hyperechoic mass. In the neonatal period, CLE is seen as a radiopaque mass on radiographs, since it is illed with luid. Gradually the luid will be absorbed and the lesion becomes lucent.121 Subsequently the affected lobe becomes hyperinlated, with hyperlucency demonstrated on conventional radiography and CT scan. The vascular markings are diminished in the affected lobe (Fig. 41-2). Associated indings are compressive atelectasis in the ipsilateral or even contralateral lobes, mediastinal shift, hemidiaphragm depression, and widening of the rib spaces.125,127,129,151 CT can also be helpful in identifying an abnormal bronchus or focal obstruction as an underlying etiology, as well as evaluating any associated mediastinal or cardiac abnormality.127 Differential diagnosis includes pneumothorax, pulmonary cysts, CPAM, and pulmonary interstitial emphysema (PIE). The pulmonary markings passing through the overinlated lung differentiate it from pneumothorax and pulmonary cysts. In CLE the septae and vascular structures are located at the periphery of expanded air spaces, whereas they are seen in the center in PIE, in which the abnormal air collection occurs in the interstitium. No associated soft tissue is seen in CLE, unlike in CPAM.47 Asymptomatic or mildly symptomatic patients are managed conservatively with low-volume and low-pressure ventilatory support given as needed. In patients with more severe respiratory distress, emergent surgical resection of the affected lobe might be needed.49

Congenital Diaphragmatic Hernia Congenital diaphragmatic hernia (CDH) is an uncommon congenital anomaly of the diaphragm with an incidence of 1 per 2000 to 3000 births.92 Normally the diaphragm starts to develop at approximately 4th week of gestation and is fully formed by the 12th week of gestation. In CDH, one of the components of the diaphragm does not form properly, creating a defect that allows abdominal viscera to enter into the thoracic cavity. This impedes normal development of the lungs, resulting in severe respiratory failure soon after birth because of pulmonary hypoplasia and the presence of pulmonary hypertension.87,101 CDH can be classiied based on the anatomic position of the defect into posterolateral, anterior, and central defects. The posterolateral defect (Bochdalek hernia) occurs in 70% to 75% of cases, anterior defects (Morgagni hernia) in 23% to 28%, and central defects in only 2% to 7% of cases. The posterolateral defect most often occurs on the left side (85%) but can occur on the right (13%) or even bilaterally (2%).101,166 CDH is associated with other congenital abnormalities in approximately 40% of cases.131 After pulmonary anomalies, cardiovascular anomalies are the most common group of congenital anomalies present in CDH infants.105 It has been shown to be associated with genetic syndromes such as Beckwith-Wiedemann syndrome and CHARGE syndrome and chromosomal abnormalities including trisomies of 13, 18, 21, and Turner’s syndrome.54,73,131 CDH can be diagnosed prenatally by ultrasonography (60% of cases) or postnatally soon after birth.62 Milder forms of CDH may present with mild respiratory or gastrointestinal symptoms after several months or even years.53 Postnatal chest and abdominal radiographs are usually diagnostic and will show an opaciied hemithorax with mass effect and contralateral shift of the mediastinum with stomach and gas-illed loops of bowel in the chest.160 Crosssectional imaging can be helpful in cases where the diagnosis is still not clear and to evaluate the spectrum of associated anomalies (Fig. 41-3). CT is useful to demonstrate any associated lung masses and

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B FIG 41-2 Congenital lobar emphysema. A, Axial CT shows hyperinlation of the posterior segment of the right lower lobe in a patient with congenital lobar emphysema. B, Sagittal CT in the same patient shows lucency and hyperinlation of the posterior segment of the right lower lobe.

bronchopulmonary foregut malformations. CT angiography is useful for depiction of the vascular supply of lung lesions. However, oral contrast material should be avoided because it can increase the mediastinal shift and subsequent respiratory compromise. If the patient is stable, MRI can be used in the evaluation of complex lesions as well. In recent years there has been an increase in the use of fetal surgery as an experimental treatment approach. The postnatal management of CDH has evolved in recent decades and now includes gentle ventilation with permissive hypercapnia and delayed surgical repair after stabilization. Prognosis of CDH is related to the degree of pulmonary hypoplasia and need for extracorporeal membrane oxygenation (ECMO) in the neonatal period.57,165 Follow-up chest imaging after surgical repair might be useful to evaluate the functional consequences of the underlying pulmonary hypoplasia and its complications. Pulmonary hypoplasia will manifest as a smaller lung with diminished pulmonary vascularity.

Pulmonary Sequestration

FIG 41-3 Congenital diaphragmatic hernia. Single-shot coronal T2weighted MRI of an approximately 28-week fetus reveals nondilated bowel illing the left hemithorax. The left lung was hypoplastic. Mediastinum was shifted rightward. Patient received surgery soon after birth.

Pulmonary sequestration is deined as a segment of lung tissue that is separate from the tracheobronchial tree and receives its blood supply from a systemic artery.61,153,152 There are two types of pulmonary sequestration: (1) intralobar, which is covered by pleura of the adjacent lung (Fig. 41-4), and (2) extralobar, which has its own separate pleural covering (Fig. 41-5).153 Intralobar sequestrations account for 75% of cases of sequestration. Both intra- and extralobar forms receive systemic arterial supply. In 80% to 90% of sequestration, the arterial supply is from the thoracic aorta (see Fig. 41-4B and C) coursing through the inferior pulmonary ligament, and in the remaining cases it is from the abdominal aorta. Venous drainage of the intralobar form is to the pulmonary vein (see Fig. 41-4C), whereas the extralobar form drains into systemic veins (see Fig. 41-5E). The extralobar form is most commonly diagnosed in the prenatal/neonatal period, and is often

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associated with other congenital systemic anomalies, such as CDH, cardiac abnormalities, pulmonary hypoplasia, or foregut duplication cysts.119 The intralobar form is usually diagnosed later in childhood or adulthood,19 usually with recurrent infections or hemoptysis. Association of intralobar sequestration with other congenital anomalies is rare.108,109 The intralobar form typically affects the posterior basal segment of the left lung in 60% of cases.126 Rarely upper lobe and bilateral lesions have been reported. The radiographic appearance is nonspeciic and depends on the degree of aeration and the presence of infection within the sequestered lung. Most pulmonary sequestrations appear as a triangular or oval mass in the medial and basal portion of a lung, more commonly on the left (see Fig. 41-5A, B and C).109 The lack of communication of the sequestered lung with the normal tracheobronchial tree is associated with continued accumulation of secretions accompanied by acute inlammation, infection, and air trapping.59 Repeated infection may establish an abnormal communication with the tracheobronchial tree and cystic bronchiectasis may ensue. In older patients the sequestration will show the effects of recurrent infections. Occasionally, calciications occur in pulmonary sequestration and are readily detected by CT.164 MDCT angiography and MRA are the imaging methods of choice in the noninvasive assessment of pulmonary sequestration, showing in excellent detail the anomalous systemic vessel.31,43,116 Systemic arterial supply originates from the lower thoracic/upper abdominal aorta and is an essential feature of pulmonary sequestration that differentiates it from other focal lesions with similar characteristics, such as CPAM (see Fig. 41-5D).5,43,116 Venous drainage is also identiied, with the intralobar form draining into pulmonary veins (see Fig. 41-4C) and the extralobar form draining into systemic veins (see Fig. 41-5E).

Scimitar Syndrome (Hypogenetic Lung Syndrome) B

C FIG 41-4 Intralobar sequestration. A, Contrast CT of chest in a 12-month-old reveals an airspace opacity in the posteromedial base of right lung (arrow). B, Axial CT also shows an obliquely coursing artery arising off the aorta, feeding this abnormal portion of lung (arrow). C, Another serpiginous contrast-enhancing structure arises from this portion and connects with a right inferior pulmonary vein (arrow). Findings suggest an intralobar sequestration.

Scimitar syndrome (hypogenetic lung syndrome, congenital venolobar syndrome) is characterized by partial anomalous pulmonary venous drainage of the lung associated with hypoplasia of the lung and pulmonary artery. It is caused by failure of integration of the primitive pulmonary venous plexus with the common pulmonary vein, resulting in communication with cardinal or umbilical veins; it is almost always seen on the right. The anomalous vein drains part or the entire right lung into the inferior vena cava (Fig. 41-6), coronary sinus, right atrium, azygos vein, portal vein, or hepatic vein. Cardiac dextroposition and systemic arterial supply to the right lung are also seen. Occasionally not all these features are present in an individual patient. Anomalies of bronchial and pulmonary arterial branching, lobes, and issures are commonly seen, including horseshoe or crossover lung. Other associations include pulmonary sequestration, aortopulmonary collateral vessels, congenital cardiac defects (e.g., atrial septal defect, hypoplastic left heart), CDH, and musculoskeletal abnormalities. Scimitar syndrome results in a left-to-right shunt, which if large or associated with pulmonary hypertension may require further treatment with surgery or embolization. On radiographs a characteristic scimitar sign is seen, which is caused by the anomalous pulmonary vein curving medially toward the diaphragm and inferior vena cava and progressively widening, giving the appearance of a scimitar (Turkish/Persian sword with a curved blade). CT and MRA are useful in accurate depiction of this anomalous venous drainage (see Fig. 41-6). MRI also helps quantiication of the left-to-right shunt using velocity-encoded phase-contrast imaging. Abnormalities of the lung, systemic arterial supply, and other associated abnormalities can also be evaluated using CT and MRI. Scimitar sign can also be seen in another entity called anomalous single pulmonary vein (ASPV) (anomalous unilateral single pulmonary vein, meandering pulmonary vein, scimitar variant, pseudoscimitar syndrome, or

A

B

C

D E FIG 41-5 Extralobar sequestration. A, Axial CT shows a luid-containing lesion in the left lower lobe adjacent to the diaphragmatic dome, consistent with extralobar pulmonary sequestration (arrow). B, Coronal CT in the same patient shows the luid-containing lesion in the left lower lobe adjacent to the left dome of the diaphragm (arrow). C, T2-weighted coronal MRI in a 6-month-old boy shows a mass in the left lower lobe adjacent to the diaphragm; this suggests an extralobar sequestration (arrow). D, Coronal time-resolved MRA image shows arterial supply to this left lower lung mass arising directly from the upper abdominal aorta (arrow). E, Venous phase image from the same MRA shows the vertically coursing draining vein (arrow), which ultimately joins the left renal vein (arrowhead).

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B FIG 41-6 Scimitar syndrome. A, Coronal MIP image from a CT scan shows a large right pulmonary vein that is extending into the right lower lobe (arrow) parallel to the right heart border and extending below the diaphragm to drain into the inferior vena cava. The right lung is hypoplastic. B, Coronal MRA image in another patient shows an anomalous pulmonary vein (arrow) that is extending below the diaphragm to drain into the portal vein (not shown here) in this patient with scimitar syndrome.

pulmonary varix), in which the entire lung is drained by a single pulmonary vein that has an anomalous course, but the main difference from scimitar syndrome is that this vein drains normally into the left atrium. It shares several common features with scimitar syndrome, including right sidedness, right lung hypoplasia, cardiac dextroposition, systemic arterial supply, branching abnormalities, and other congenital defects. ASPV is caused by hypoplasia/atresia of one of the pulmonary veins before pulmonary segmentation, as a result of which drainage of the entire lung occurs through the remaining vein. Since ASPV is not a shunt, it does not require further investigation or treatment. Other differential diagnoses for scimitar sign include pulmonary sequestration, pulmonary varix, and pulmonary nodule/mass.

Pulmonary Arteriovenous Malformation Pulmonary arteriovenous malformations (AVMs) are vascular communications between a pulmonary artery and vein (95%) bypassing the capillary bed. Pulmonary AVMs are usually congenital but may also be idiopathic, occur as a result of trauma and infection, or be secondary to hepatopulmonary syndrome and bidirectional cavopulmonary shunting. About 60% of pulmonary AVMs are associated with RenduOsler-Weber syndrome (hereditary hemorrhagic telangiectasia),44 and 15% of hereditary hemorrhagic telangiectasia patients have pulmonary AVM.66 This is an autosomal dominant disorder caused by genes that encode transforming growth factor binding protein,114 with associated abnormalities in liver, skin, brain, and gastrointestinal tract. Owing to this high association, screening for pulmonary AVM is indicated in this subgroup. Physiologic consequences of pulmonary AVM depend on the degree of right-to-left shunt and include hypoxemia, dyspnea, and cyanosis. Hereditary pulmonary AVMs tend to increase in size over time, with clinical manifestations usually presenting by the ifth decade. These patients are also prone to paradoxical embolization complications including stroke and brain abscess.28,146 The typical CT features of pulmonary AVM are: smooth lobulated oval/round mass (Fig. 41-7A) or even serpiginous nodule, less than 1 cm to several centimeters in size, associated with a visible enlarged feeding artery and an enlarged draining vein (see Fig. 41-7B). The feeding artery usually has less than half the diameter of the nodule.95,96,175 Complex AVMs having more than one feeding artery are rare.135,136 The

most common location is the lower lobe.44 CT or MR pulmonary angiography can be used to conirm the vascular nature of the lesion. Multiple AVMs can be confused with metastases if the enlarged feeding vessels are overlooked. MIP reconstructions can also be obtained to scrutinize the pulmonary parenchyma for malformations and depict the size and number of the supplying arteries.175 Pulmonary AVMs can be successfully treated with embolotherapy.21,58,134

Bronchial Atresia Congenital bronchial atresia is a rare anomaly resulting from focal obliteration of a segmental (less commonly a subsegmental) or lobar bronchus that lacks communication with the central airways.16,93,122,178 The bronchi distal to the stenosis are dilated and illed with mucus, forming a bronchocele. The alveoli supplied by these bronchi are ventilated by collateral pathways and show features of mild air trapping, resulting in a region of hyperinlation around the dilated bronchi.33 The upper lobe bronchi are more frequently affected, particularly the apicoposterior segment of the left upper lobe; middle and lower lobes are rarely affected.178 In some cases, bronchial atresia may be acquired postnatally owing to traumatic or postinlammatory insult to the bronchus.83 Bronchial atresia is usually asymptomatic and is found incidentally in chest radiographs; however, dyspnea, pneumonia, and bronchial asthma have been reported.16 In bronchial atresia the airway is occluded rather than narrowed; consequently there is no ball-valve effect as seen in CLE. Hence the lobe or segment does not become nearly as hyperinlated as with CLE. The characteristic chest radiographic indings consist of a bronchocele, seen as rounded branching opacities radiating from the hilum, that may contain an air-luid level. The distal lung is emphysematous and produces an area of hyperlucency around the affected bronchi. In newborns the affected segment contains fetal lung liquid trapped behind the atresia and may be seen as a luid-illed mass.16 CT is a sensitive modality for demonstrating the typical features of bronchial atresia. It shows a round opacity at the site of the atresia, medial to the air trapping caused by a mucus plug, which can be clearly depicted by performing expiratory CT15 (Fig. 41-8). CT is also excellent for excluding the presence of a hilar mass and precisely determining the location of lesions. In doubtful cases, multiplanar reformation helps distinguish

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B FIG 41-7 Pulmonary arteriovenous malformation. A, Axial CT shows an irregular enhancing mass in the periphery of the left lung (arrow); appearances consistent with arteriovenous malformation. B, Coronal MIP of the same patient demonstrates post-embolization appearances of this arteriovenous malformation (arrow).

FIG 41-8 Bronchial atresia. Axial CT shows an area of mucoid plugging in the left lower lobe (white arrow), and distal to this there is an area of hyperlucency (black arrow), consistent with bronchial atresia.

mucoid impaction from nodular lesions. CT also shows the obstruction, associated segmental hypoattenuation, decreased vascularity, and possible proximal bronchocele or broncholith. When the location is basal, spiral CT with contrast can easily exclude a vascular component that could indicate pulmonary sequestration.15 MRI shows the bronchocele as a branching structure radiating from the hilum, with high signal intensity on T1- and T2-weighted images; however, MRI cannot depict regional air trapping.16 The major indication for surgery in these patients is recurrent infection.19

Cystic Fibrosis Cystic ibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene and the most common lethal genetic disease in Caucasians. CF is a multisystem disorder of exocrine gland function,

with resultant abnormal viscosity of mucus and decreased mucociliary clearance. In the respiratory tract these conditions result in recurrent lung infection and chronic sinusitis with nasal polyps.124,171 Lung involvement is the main cause of morbidity among patients with CF.124 Improvements in therapeutic options have substantially increased the life expectancy of CF patients, with a current median survival of approximately 40 years, which is expected to increase even further.51,64,150 Until 2 decades ago, chest radiograph was the most widely used imaging to monitor morphologic changes in the CF lung. Although chest radiograph correlates signiicantly with pulmonary function test parameters, it has a low sensitivity to detect early changes in the CF lung.161,162 Currently, HRCT is recognized as the gold standard for assessment of morphologic changes of the airways and lung parenchyma for both early diagnosis and monitoring of CF lung disease38,39,148,163 with higher sensitivity than chest radiograph and lung function testing.17,22,23,41,80 Therefore, multiple disease-scoring systems based on HRCT indings have been proposed.17,25,69,144 An HRCT inding in early stages of lung involvement in CF is a mosaic attenuation pattern resulting from air trapping related to small airway disease.22 Other typical features that may be seen during the course of the disease include bronchiectasis (Fig. 41-9) and peribronchial thickening, mainly involving the upper lobes, and centrilobular nodules and a tree-in-bud pattern secondary to mucous plugs.22,23 Development of bronchiectasis in CF is almost universal, detected in approximately 30% of children with normal indings at lung function testing.22 Bronchiectasis alone or in combination with mucus plugging is given the highest weighting in most scoring systems and is thus commonly considered to be the most signiicant inding when evaluating CF lung disease.168 Pneumothorax is a rare complication with an incidence of 0.64% per year among CF patients.120 Considering the necessity of lifelong repeated imaging studies, MRI has been proposed as a radiation-free alternative to CT.27 Although spatial resolution is lower as compared to CT, MRI has the advantage of higher soft tissue characterization and visualizing different regional functional aspects of the lung parenchyma (pulmonary hemodynamics, perfusion, and ventilation).51,158,177 Using common MRI sequences, it is possible to visualize bronchiectasis/bronchial wall thickening, mucus plugging, air-luid levels, consolidation, and segmental/lobar destruction.132

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older adolescents, Mycoplasma is the commonest, but C. pneumoniae and fungal infections can be seen. Pneumonia is seen on radiographs, but CT is performed when (1) there are persistent signs, symptoms, and radiographic indings not responding to treatment; (2) to exclude underlying lesions such as sequestration; and (3) to evaluate complications such as pleural effusion, abscess, and empyema. CT is performed when radiographic indings are normal, equivocal, or nonspeciic. CT is more sensitive than radiographs in the detection of pneumonia. CT indings of pneumonia include air space disease (Fig. 41-10), consolidation, ground-glass opacities, air bronchograms, air space nodules, and centrilobular or perilobular distribution.

Round Pneumonia. Round pneumonia is a community-acquired

A

B FIG 41-9 Cystic ibrosis. A, Coronal CT in a patient with cystic ibrosis shows extensive cystic bronchiectatic changes predominantly seen in the upper lobes, along with bronchial thickening. The lungs are hyperinlated. B, Axial CT in the same patient shows extensive bilateral upper lobe–predominant bronchiectatic changes along with bronchial thickening and areas of mucoid plugging.

INFECTIONS Pneumonia Pediatric pneumonia is most commonly caused by Streptococcus pneumoniae. Other organisms include Mycoplasma pneumoniae and Chlamydophila pneumoniae and viruses. In newborns, group B Streptococcus, Listeria monocytogenes, or gram-negative rods are common bacterial agents. In children aged 1 to 3 years, the most common organisms are S. pneumoniae, Staphylococcus aureus, and Haemophilus inluenzae. In infants, toddlers, and preschool-aged children, viruses are the most common pathogens, with respiratory syncytial virus (RSV) followed by parainluenza type 1, 2, 3 and inluenza A and B. S. pneumoniae is the most common bacterial pathogen. In school-aged children and young adolescents, Mycoplasma is the most common organism, with others being S. pneumoniae, S. aureus, and Streptococcus pyogenes. In

pneumonia manifesting as a rounded opacity on imaging.138 It is more common in children younger than 12 years.85 It is usually caused by bacterial infection, most commonly S. pneumoniae (90%). In older children, especially those with immunodeiciency, fungal or mycobacterial infections are occasionally encountered.170 Smaller alveoli, closely apposed septa, and underdeveloped interalveolar connections constrain the spread of infection to adjacent alveolar sacs in young children, resulting in a round opacity on imaging. Patients present with clinical signs and symptoms of pneumonia. The characteristic inding is a solitary circumscribed spherical opacity, with predilection for the posterior segment of the lower lobes. The lesion is usually in contact with the pleura or hilum. Air bronchograms are seen in 20% of cases. Satellite lesions are sometimes present, but multiple round pneumonias are rare (1%). Calciication, cavitation, lymphadenopathy, or pleural effusion are not characteristically present.137 In a child presenting with clinical symptoms of pneumonia, a rounded opacity on radiograph or CT scan (Fig. 41-11) is indicative of round pneumonia. A rounded opacity in adults could be neoplastic, but in children it is almost always benign.169 There are other entities mimicking round pneumonia, such as inlammatory masses (e.g., lung abscess, tuberculosis, fungal infection), congenital anomalies, neoplasms, and pseudomasses.35,50,70,142 CT should be considered for further evaluation of a radiographic round opacity in the following settings: clinical features not consistent with a pneumonic process, persistent opacity after appropriate antibiotic treatment, radiographic signs of nonpulmonary origin, or immunocompromised patient with suspicion of complicated infection.137

Pneumonia with Cavitary Necrosis. Cavitary necrosis (necrotizing pneumonia) is one of the parenchymal complications of severe pneumonia. The spectrum of parenchymal complications of pneumonia also includes lung abscess, pneumatocele, and bronchopleural istula.48 In adults, necrosis and cavitation are usually associated with S. aureus, Pseudomonas aeruginosa, Klebsiella, and anaerobic infection, but in children S. aureus or S. pneumoniae are most commonly involved. Cavitary necrosis is demonstrated as a dominant area of nonenhancing necrosis surrounded by a thin wall or without a wall within a parenchymal consolidation. Lung abscess is characterized as a solitary cavity with a thick enhancing wall (Fig. 41-12).72 Pneumatocele presents at later stages of healing necrosis. Although children with necrotizing pneumonia typically have a prolonged and intense course of illness, most will ultimately recover without the need for surgical intervention.76

Parapneumonic

Effusion/Empyema. Parapneumonic effusion (PPE) or empyema complicates pneumonia in 28% to 53% of pediatric cases.24 Although the overall incidence of bacterial pneumonia has been declining in children following the introduction of pneumococcal conjugate vaccine, the incidence of PPE and empyema has

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B FIG 41-10 Pneumonia. A, Axial CT shows an area of consolidation with air bronchogram in the left lower lobe (arrow) consistent with pneumonia. B, Coronal CT in the same patient shows the consolidation with air bronchogram in the left lower lobe.

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B FIG 41-11 Round pneumonia. A, Axial CT shows a well-deined round area of consolidation in the periphery of the right lower lobe (arrow) in a 7-year-old boy. B, Coronal CT in the same patient shows the welldeined round pneumonia in the right lower lobe (arrow).

increased.78,79,65,103 S. pneumoniae remains the leading pathogen, but the incidence of empyema caused by other pathogens such as Staphylococcus has increased.65 Despite the low mortality and favorable outcome in most cases as compared to adults,12 complicated PPE causes signiicant morbidity in children. Four progressively complex stages characterize parapneumonic pleural disease: (1) precollection stage (pleuritic), (2) exudative stage with free-lowing pleural luid and low white count, (3) ibrinopurulent stage or complicated PPE with deposition of ibrin and purulent material, (4) organizational stage with thick pleural peel.67 Chest radiograph is often the initial imaging modality, but in many cases it cannot differentiate pulmonary parenchymal disease from pleural disease. Ultrasound and CT can reliably differentiate these two entities.78 CT scan is reserved for special cases such as where characterization of the extent of the parenchymal disease and/or the presence and location of lung abscesses will affect presurgical planning.78 Neither ultrasound nor CT can reliably differentiate between different stages of the PPE (Fig. 41-13); a pleural tap is required to identify complicated PPE or empyema. On CT, PPE or empyema is seen as thickened and enhancing pleural layers surrounding a pleural effusion, resulting in the split pleura sign (Fig. 41-14). Pleural thickening and enhancement are seen in 86% to 100% of cases of empyema, compared with 60% of parapneumonic effusions. Although pleural thickness appears to increase on CT with advancing disease, it indicates neither a poor response to therapy nor the need for surgical intervention. Empyema is also associated with thickened extrapleural soft tissue and increased attenuation of extrapleural fat (an increase of >50 HU compared with fat posterior to the spine). These changes may persist for some time after resolution of the infection. Nodal enlargement of less than 2 cm is common in empyema and tends to be seen in ipsilateral subcarinal and paratracheal nodes, more often on the right. The amount of nodal involvement is not associated with more advanced disease. CT demonstrates separate loculations of infected pleural luid in about 20% of cases, which helps in deciding the optimal placement of a chest drainage catheter, particularly in patients who are not responding to conventional therapy or in whom drainage has ceased. Septations within the same luid collection may be demonstrated on CT, signiied by the presence of trapped pockets of air within a luid collection. Up to 30% of patients with empyema fail conservative medical therapy (antibiotics

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FIG 41-12 Pneumonia with lung abscess formation. A, Axial CT shows a large irregular gas-containing cavitary lesion in the left lower lobe (arrow) consistent with a lung abscess. B, Coronal CT shows a large thickwalled abscess cavity in the left lower lobe (arrow) with surrounding areas of consolidation. C, Axial CT in another patient shows a large luid-containing lesion in the right lung (arrow) with thick walls and surrounding consolidation, consistent with lung abscess. D, Coronal CT shows a large thick-walled cavitary lesion with gas bubbles (arrow) consistent with a lung abscess.

and intercostal drainage) and require surgery. CT is useful in surgical planning of these patients. Distinguishing empyema from a pulmonary abscess abutting the pleural surface is important because empyema is treated with drainage, whereas an abscess is generally not drained to avoid the risk of pleural spread. On contrast CT, empyema is lenticular, thin walled with compression of adjacent lung structures, and increased attenuation of extrapleural fat. Abscesses are spherical thick-walled lesions associated with abrupt vessel cutoff and the presence of bronchi at the interface of the abscess and normal lung. MRI is not routinely used for assessment of patients with pleural infection owing to its poor spatial resolution and higher likelihood of motion artifact compared with CT. However, MRI is a sensitive technique for demonstrating septations within a pleural collection and may be used if contrast administration is contraindicated or if there is concern about radiation exposure. Rarely malignancies may arise in the wall of chronic empyema cavities and are detected by MRI, which allows differentiation of ibrous from neoplastic tissue. Malignancies associated with chronic empyema include non-Hodgkin’s lymphoma, squamous cell carcinoma, mesothelioma, and sarcoma.

TRAUMA Blunt Trauma Rib fractures can be seen following trauma (Fig. 41-15). Pulmonary contusion is the most common lung injury from blunt chest trauma, occurring at the time of injury. On CT, patchy airspace opacities or consolidation with ill-deined margins is seen in a nonsegmental distribution with subpleural clearing (Fig. 41-16A). Contusion appears immediately, resolution begins in 24 to 48 hours, and complete clearing takes 3 to 10 days.81 Pulmonary laceration is a tear in the lung, with a resulting cavity. The cavity results from normal lung recoiling back from the laceration. On CT, single or multiple, unilocular or multilocular, round or oval cavities may be seen. The cavity may be illed with air (pneumatocele) (see Fig. 41-16B), blood (hematocele), or both. Lacerations heal slowly and take months.81 There are four types of lacerations based on mechanism, CT appearances, and location of rib fractures. Type I is caused by compressive forces causing lacerations in deep portions of lung, type 2 by compression shear injury with sudden shift of lower lobes across the spine, type 3 by a rib fracture

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FIG 41-15 Traumatic rib injury. Axial CT shows a nondisplaced fracture of the anterior aspect of the left irst rib (arrow).

A

penetrating the periphery of the lung, and type 4 is seen at the site of a preexisting pleuropulmonary adhesion.81 Pneumothorax can be caused by alveolar rupture due to sudden increase of intrathoracic pressure or blunt crushing force or deceleration.

Nonaccidental Trauma

B FIG 41-13 Parapneumonic effusion. A, Axial CT shows an area of consolidation (black arrow) in the left lower lobe, with associated parapneumonic effusion (white arrow). B, Coronal CT in a 21-month-old boy shows a large consolidation in the right lung (black arrow) with associated parapneumonic effusion (white arrow).

Nonaccidental trauma (battered baby syndrome, shaken infant syndrome) in infants and young children is due to abuse. The classic pattern of injuries is seen when the child is violently shaken while being held around the chest. In children with suspected nonaccidental injury (NAI) a skeletal survey is typically performed to evaluate all the injuries. However, sometimes the radiographic indings may be subtle or negative, warranting additional evaluation with CT. Occasionally these injuries may also be incidentally seen on CT and MRI. In such scenarios, maintaining a high level of suspicion, particularly when the injuries could not be explained by the reported mechanism, is essential for making a prompt diagnosis and alerting authorities. Owing to plasticity of ribs, fractures are generally uncommon in infants and children younger than 3 years, even in accidents and after cardiopulmonary resuscitation. Rib fractures, particularly those of the posterior (Fig. 41-17) and costochondral junctions, are highly speciic for NAI. Rib fractures are the most common skeletal injury in NAI and are seen in 80% of these children181; in 29%, rib fracture may be the only skeletal abnormality. Although rib fractures are seen on radiographs, CT is performed when the radiograph is negative/subtle because of acute nondisplaced, incomplete, oblique fractures, which may be obscured by superimposed structures. CT has been shown to be more sensitive than radiographs in such situations.181 Fractures of the sternum and scapula are also suggestive of NAI.

NEOPLASMS Primary lung tumors are rare in children, with most lung masses likely benign developmental or reactive, which are 10 times more common.45 Of the neoplasms, metastasis is more common than primary lung tumors, and malignancies are three times as common as benign lesions. Inlammatory myoibroblastic tumor is the most common benign tumor, and pleuropulmonary blastoma and carcinoids are the most common primary malignancies.45

Pulmonary Blastoma

FIG 41-14 Empyema. Axial CT shows a thick-walled left pleural luid collection showing the so-called split pleura sign of thickened and enhancing pleural layers, consistent with empyema (arrow).

Pulmonary blastoma is a rare malignancy that accounts for 0.25% to 0.5% of primary lung tumors.60,89,94,102 The tumor derives its name from its histologic resemblance to fetal lung tissue. Pulmonary blastomas, however, are thought to arise from primitive pluripotential stem cells and may represent a variant of carcinosarcoma.176 Although the age

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B FIG 41-16 Contusion and pneumatocele. A, Axial CT in a 12-year-old boy with a history of trauma shows an area of ground-glass opacity in the left lower lobe (arrow), consistent with pulmonary contusion. Note also a small left pneumothorax. B, Axial CT in the same boy shows that there is an air-containing focus (arrow) within the ground-glass opacity, consistent with a pneumatocele.

range at presentation is wide (0-80 years), these tumors typically occur in adults, with a peak incidence between the age of 40 and 60 years.60,89,94,102 Patients are often symptomatic at presentation; cough, hemoptysis, and chest pain are frequent manifestations.89,102 Pediatric patients typically present with fever and respiratory distress.20 The behavior of pulmonary blastoma is aggressive, and the outcome is poor owing to frequent relapses and metastases.18,20,34 Radiologically, pulmonary blastomas typically manifest as large (2.5-26 cm) well-marginated masses located peripherally in the lung20,104,173 (Fig. 41-18). Multiple masses, cavitation, and calciication are rare.173 Local invasion of the mediastinum and pleura occurs in 8% and 25% of cases, respectively.60 Metastases to hilar and mediastinal lymph nodes are present in 30% of resected cases.60 Extrathoracic metastases are common and have a distribution similar to that of lung cancer.60,102

Pulmonary Inlammatory Pseudotumor Inlammatory pseudotumor (IPT) or inlammatory myoibroblastic tumor (plasma cell granuloma) is characterized by a proliferation of ibroblasts and myoibroblasts mixed with varying numbers of plasma cells, lymphocytes, macrophages, and other inlammatory cells.10,184 Historically, IPT has been believed to be a nonneoplastic reactive lesion simulating a neoplasm; however, over the past 15 years or so, almost all IPTs have been regarded as true neoplasms.149 Currently they are generally considered as a soft tissue mesenchymal tumors with indeterminate or low malignant potential.32 In fact the current World Health Organization classiication of lung tumors adopted the name inlammatory myoibroblastic tumor (IMT) as the preferred term for these lesions. Other synonyms used for IPT are plasma cell granuloma, plasma cell pseudotumor, inlammatory myoibrohistiocytic proliferation, xanthoibroma, and omental mesenteric myxoid hamartoma. IPT was irst described in the lungs, but several reports have described them in almost all other organs. Based on major histopathologic features, IPT can be divided to three categories: organizing pneumonia type, ibrous histiocytoma type, and lymphoplasmacytic type.110 Pulmonary IPT is a rare disease.30 It affects both sexes at any ages, with a predominance in children and young adults.68 Patients are aflicted with nonspeciic symptoms such as cough, dyspnea, hemoptysis, chest pain, fever, and fatigue. Weight loss and anorexia are rare. However, most patients are asymptomatic and the tumor is discovered

incidentally on a chest x-ray performed for another reason. Radiologic aspects are variable and nonspeciic. Most patients have a parenchymal pulmonary mass or nodule (85%). IPT can also present as endobronchial (11%) or endotracheal (4%) polypoid lesions.84,86 They are mostly solitary, rarely multiple (5%), 1 to 6 cm in diameter, well circumscribed, smooth, or bumpy (Fig. 41-19). Parenchymal lesions are predominantly located on the periphery, with a predilection for the lower lobes.4 CT shows the presence of a heterogeneous nodule or mass with variable contrast enhancement. CT speciies the solid or cystic nature of the tumor, its vascular behavior, and assesses the locoregional extension. Calciications (15%) and cavitations are uncommon.82,110,115 MRI shows intermediate signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging. Various contrast enhancement patterns have been described.4,159 Pleural effusion is seen in less than 10% and atelectasis in 8% of cases. IPT is usually a slow-growing tumor; however, case reports of fast-growing cases are also present.182 Sometimes the tumor can extend toward the hilum, mediastinum, pleura, or diaphragm. Because of the diversity of clinical and radiologic manifestations of IPT, diagnosis is based on histologic examination of the surgically resected specimen. Currently the principal management of IPT—for diagnostic and therapeutic reasons—is a complete resection. Incomplete resection increases the risk of recurrence. Corticosteroids are generally not useful in adults, but good results have been reported in children in cases of unresectable tumors or hilar and mediastinal invasion. Chemotherapy is useful in cases of multifocal invasive lesions or in cases of local recurrence.68

Metastasis Metastasis accounts for 80% of lung tumors in children.45 Tumors that spread to lung are osteosarcoma, Wilms’ tumor, neuroblastoma, Ewing’s sarcoma, rhabdomyosarcoma, other soft tissue sarcomas, hepatoblastoma, thyroid carcinoma, and adrenocortical carcinoma. On CT, pulmonary metastasis is seen as multiple soft tissue nodules of variable sizes, more on the periphery of the lung, usually in lower lobes in those with hematogenous spread (Fig. 41-20). Solitary pulmonary nodule, miliary nodules, cavitation, calciication, and ground-glass opacity are atypical indings. A reticular or miliary pattern is seen in lymphangitic spread. Cavitation and pneumothorax is associated with osteosarcoma, Wilms’ tumor, and Hodgkin’s lymphoma.45

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B FIG 41-17 Nonaccidental injury. A, Axial CT shows a nondisplaced fracture of the left posterior sixth rib (arrow). B, Coronal CT in another patient shows multiple nondisplaced posterior rib fractures (arrows).

AIRWAY ABNORMALITIES Tracheal Bronchus Tracheal bronchus (so-called pig bronchus, or bronchus suis) is a congenital branching anomaly in which the upper lobe bronchus arises directly from the trachea and above the level of the carina16,63,123 (Fig. 41-21). The incidence of tracheal bronchus ranges between 0.1% and 5% in the general population.91 It is most common on the right side, with the right upper lobe bronchus originating from the right tracheal wall. Tracheal bronchus is usually diagnosed incidentally during bronchoscopy or CT performed for evaluation of various causes of respiratory symptoms. However, tracheal bronchus may also be the cause of recurrent atelectasis or pneumonia in the upper lobe in symptomatic pediatric patients.16 Treatment is not required in asymptomatic

C FIG 41-18 Pulmonary blastoma. A, Axial CT in an 18-month-old boy shows a large tumor almost completely replacing the left lung, which shows heterogeneous contrast enhancement (arrow) and displacement of the mediastinum to the right. B, Axial CT in the same patient at a higher level shows the heterogeneously enhancing mass in the left lung (arrow). C, PET-CT image of the same patient showing intense FDG uptake within the mass (arrow), which was shown to be pulmonary blastoma.

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B FIG 41-19 Pulmonary inlammatory pseudotumor. A, Axial CT shows a heterogeneously enhancing peripheral mass in the right lower lobe (arrow). B, Coronal CT shows a heterogeneously enhancing peripheral mass in the right lower lobe (arrow), which was shown to be a pseudotumor.

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B FIG 41-20 Metastasis. A, Axial CT shows multiple solid metastatic lesions along with a large cystic component in the left lower lobe in a patient with sarcoma of the soft tissue. B, Coronal CT in the same patient shows multiple solid metastatic lesions in both lungs.

patients, but in symptomatic patients, surgical resection of the aberrant bronchus and its lobe is currently recommended.99

tracheal stenosis is caused by extrinsic compression by vascular ring/ sling or a dilated esophagus.

Tracheal Stenosis

Tracheobronchomalacia

Tracheal stenosis in children can be congenital, caused by replacement of the posterior tracheal membrane with cartilages. This may affect over 50% of the tracheal lumen and may involve the bronchi as well (Fig. 41-22). On CT, an O-shaped trachea is seen. Associated anomalies may be seen in the cardiovascular or musculoskeletal systems. Acquired

Tracheobronchomalacia refers to expiratory collapse of the tracheobronchial tree. It can be caused by congenital softening of the cartilaginous rings in the anterior two thirds of the tracheobronchial wall. It is also associated with CF, Mounier-Kuhn syndrome, Marfan’s syndrome, Ehlers-Danlos syndrome, and Cornelia de Lange syndrome. It

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CT and MR Imaging of the Whole Body infants and children with a reliable history and high clinical suspicion of foreign body aspiration. Approximately 10% of aspirated foreign bodies within the trachea and bronchi are radiopaque and can be detected on chest radiographs.145 The sensitivity and speciicity of correctly diagnosing foreign body aspiration with chest radiographs in pediatric patients are 68% to 74% and 45% to 67%, respectively.147,157 Therefore, pediatric patients who present with typical clinical symptoms and high clinical suspicion of foreign body aspiration should be further evaluated with either CT or conventional bronchoscopy after negative chest radiographs.11,90,98,100 Although CT is currently the most sensitive imaging modality for detecting foreign body aspiration (accuracy close to 100% in pediatric patients), judicious use of CT is advised and only recommended for cases where chest radiographic indings are negative or equivocal.98 On CT, foreign body aspiration can be diagnosed or suspected when there is an endoluminal mass with various attenuation within the airways.98,100 Secondary CT imaging indings that can further support the diagnosis include postobstructive air trapping, atelectasis, and consolidation.98,100

FIG 41-21 Tracheal bronchus. Coronal CT shows the tracheal bronchus (bronchus suis) (arrow) originating from the trachea and supplying the right upper lobe.

can be caused by extrinsic compression by vascular rings/slings. It may be asymptomatic or associated with dyspnea, cough, and recurrent respiratory infections. CT with inspiratory and expiratory acquisitions is required for diagnosis. On the expiratory image, over 50% collapse of the airway compared to inspiration is diagnostic of tracheomalacia. A cutoff of 70% is more speciic in children (Fig. 41-23). Dynamic volumetric acquisition is more sensitive in direct visualization of the airway collapse. On inspiratory images, a dilated trachea with posterior bowing may be seen.

Bronchiectasis Bronchiectasis is characterized by irreversible bronchial dilation and airlow obstruction (Fig. 41-24) and can be focal or diffuse. Congenital causes of bronchiectasis include CF, ciliary dyskinesia (see Fig. 41-24C), Young’s syndrome, Marfan’s syndrome, agammaglobulinemia, immunoglobulin deiciencies, Mounier-Kuhn syndrome, and WilliamsCampbell syndrome. Acquired causes include infection (see Fig. 41-24B), chronic aspiration, and airway obstruction. Morphologically, bronchiectasis can be cylindrical (straight, uniform), varicose (bulbous, alternating dilation and constriction), or cystic (saccular; ballooned appearance with neovascularization and ulceration). On CT, bronchiectasis is seen as dilation of the bronchi (>1.5 times the corresponding vessel) resulting in a signet ring sign, grapelike clusters of dilated large airways, and airways seen up to the periphery of the lung (see Fig. 41-24A). Air trapping is seen with airway obstruction.

Bronchial Foreign Body Foreign body aspiration is a frequent cause of acute respiratory distress in children55,99 and is the ifth most common cause of death in infants.99 It is more common between 6 months and 3 years of age.98,100 Common locations of foreign body lodgment are the right main bronchus (52%), left main bronchus (18%), and trachea (13%).55 The right main bronchus is more commonly affected because it is more directly in line with the trachea in an upright position, and the left main bronchus is smaller in caliber in comparison. Affected children frequently present with coughing, wheezing, and stridor after an acute choking episode.55,133,139,145 However, children with foreign body aspiration may be asymptomatic; therefore thorough investigation is necessary in

MEDIASTINAL LESIONS Several mediastinal lesions occur in children. Anterior mediastinal masses include thymic hyperplasia, thymolipoma, lymphoma, germ cell tumor, and lymphangioma. Middle mediastinal masses include foregut duplication cysts, lymph nodal lesions such as granulomas, fungus, tuberculosis, metastasis, and lymphoma/leukemia. Posterior mediastinal masses include neurogenic tumors (95%), which involve the ganglion cells (neuroblastoma, ganglioneuroblastoma, ganglioneuroma) or nerve sheath (neuroibroma, schwannoma), and extramedullary hematopoiesis.

Anterior Mediastinal Lesions Thymic hyperplasia is characterized by an increased volume (>50%) of the thymus. Maximal and mean normal thymic thickness on the inspiratory phase of CT are 1.8 and 1.1 cm, respectively, between ages 6 and 19 years, and 1.3 and 0.5 to 0.8 cm, respectively, in adults older than 20 years.1 Thymic hyperplasia is seen in hyperthyroidism, acromegaly, Addison’s disease, stress, chemotherapy, radiotherapy, and myasthenia gravis. Distinguishing hyperplasia from a neoplasm is critical, particularly in patients who have received chemotherapy and radiation. Hyperplastic thymus maintains normal shape and has homogeneous attenuation (Fig. 41-25A) and signal. Asymmetry of the lobes, focal contour abnormalities, round soft tissue mass larger than 7 cm, and heterogeneity on MRI or CT suggest neoplasm. Signal drop in opposedphase images as compared to in-phase images (see Fig. 41-25B and C) indicates normal thymus or thymic hyperplasia due to the presence of interspersed fat, whereas neoplasms do not show this signal drop. Chemical shift ratio (CSR) is calculated as (thymus SI OP/paraspinal muscle SI OP)/(thymus SI IP/paraspinal muscle IP). Thymic hyperplasia has a CSR of 0.5 to 0.6, whereas thymic neoplasms have CSRs of 0.9 to 1.0.74 Patients with thymic hyperplasia have homogeneous luorodeoxyglucose (FDG) uptake, whereas patients with thymoma have more focal FDG uptake, which is also higher than in hyperplasia (see Fig. 41-25D). Progressive decline in size of the thymus over 3 to 6 months indicates hyperplasia. Absence of active disease is another indication. Thymic cyst accounts for 3% of anterior mediastinal masses.156 It can be congenital, caused by a remnant of the thymopharyngeal duct,183 or secondary to inlammation/neoplasm.14,75 On CT, thymic cysts are less than 6 cm, homogeneous with water attenuation, and thin walled without contrast enhancement. Proteinaceous content may give

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B FIG 41-22 Tracheal stenosis. A, Axial CT shows severe narrowing of the trachea at the level of thoracic inlet (arrow) approximately 7 cm from the glottis. B, Coronal MiniP image shows severe narrowing (arrow) at the level of thoracic inlet. C, A 3D volume-rendered image shows severe narrowing of the trachea at the level of thoracic inlet (arrow).

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B FIG 41-23 Tracheobronchomalacia. A, Axial image at the level of thoracic inlet shows normal caliber of the tracheal lumen. B, Axial image at the same level obtained at expiration shows severe narrowing of the lumen—90% greater than that in inspiration—consistent with tracheomalacia.

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C FIG 41-24 Bronchiectasis. A, Axial CT shows multiple dilated cylindrical bronchiectasis in a 7-year-old patient. B, Axial CT in another patient shows a focal area of bronchiectasis in the medial right lower lobe (arrow), which is a sequel of previous infection. C, Axial CT shows extensive cystic bronchiectasis in the lingula (arrow), with associated consolidation and also dextrocardia, which is seen with immotile cilia syndrome.

a hyperdense appearance.7 On MRI, it has low signal in T1-weighted and high signal in T2-weighted images. High T1 may be due to hemorrhage and protein. No contrast enhancement is seen. Thymolipoma is a fat-containing tumor in the thymus (Fig. 41-26). It does not have a capsule. It has soft tissue and fat elements, with heterogeneous enhancement. There is no calciication and mass effect. Lipoma may also originate from the mediastinum or extend from the neck into the mediastinum. This contains fat attenuation in CT and signal characteristics of fat in all sequences (Fig. 41-27). Thyroid lesions may also extend into the superior mediastinum (Fig. 41-28). Lymphoma is the most common mediastinal mass in children, with Hodgkin’s lymphoma more common than non-Hodgkin’s lymphoma. It is more common in the second decade. Some 70% of children with Hodgkin’s disease have thoracic disease, with the most common pattern being involvement of the mediastinal lymph nodes (95%) followed by involvement of thymus (90%), hilar nodes (25%), and lung (10%). On CT and MRI, discrete enlarged lymph nodes or a

conglomerate mass may be seen, with minimal contrast enhancement and compression of adjacent structures such as airways and vasculature (Fig. 41-29). Non-Hodgkin’s disease occurs in the irst and second decades. It most commonly involves the nodes and is not contiguous. It often spares the thymus. Germ cell tumor is the second most common cause of anterior mediastinal mass in children and the common cause of a fat-containing anterior mediastinal lesion. The majority (90%) of these lesions are benign and originate from the thymus. Teratoma has well-deined margins and is cystic with variable amounts of water, calcium, fat, and soft tissue. Size is variable and not an indicator of malignancy. Mature teratomas can also be large but are usually benign (Fig. 41-30). Malignant teratomas account for 10% of teratomas and have more soft tissue component, nodular component, invasive margins, invasion of adjacent structures, and metastatic lesions. Nonteratomatous germ cell tumors are choriocarcinoma, yolk sac tumor, and embryonal cell cancer.

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D FIG 41-25 Thymic hyperplasia. A, Axial CT shows an enlarged thymus that has sharp and smooth margins (arrow). B, In-phase T1-weighted MRI shows intermediate to high signal in the thymus (arrow). C, Opposedphase MRI shows dropout of signal in the thymus, indicating hyperplasia (arrow). D, FDG PET shows homogeneous FDG uptake in the hyperplastic thymus (arrow).

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B FIG 41-26 Thymolipoma. A, Axial CT shows a large fat-containing lesion in the anterior mediastinum (arrow). B, Coronal CT shows a huge fat-containing mass in the anterior mediastinum, proven on biopsy to be a thymolipoma (arrow).

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Lymphatic malformation (previously called lymphangioma) is a benign mediastinal lesion; 75% of these occur in the neck, 20% in the axillary region, and 5% in mediastinum,130 with a majority of them extending from the neck usually into the superior or anterior mediastinum. It is more common in males younger than age 2. On CT it is seen as a lobular multicystic mass with 1- to 2-cm cysts that iniltrates adjacent structures (Figs. 41-31). A solid appearance may be seen owing to protein/hemorrhage. Enhancement may be seen. On MRI, it has variable T1 signal, usually low to intermediate, but can contain focal areas of high signal intensity similar to fat. High signal is seen on T2-weighted images.143 Hemangioma is rare in the mediastinum (1 month), emphysematous alveoli are seen. Pulmonary hypertension and cor pulmonale may be seen. On CT scan in stage 1, changes of respiratory distress syndrome, pneumothorax, and PIE are seen. In stage 2, interlobar septal thickening is the common inding. Expiratory air trapping (Fig. 41-44), hyperinlation, atelectasis, consolidation, prominent pulmonary arteries, and enlarged heart are seen. In severe cases there is marked distortion of lung parenchyma, large cysts, coarse ibrosis, and pulmonary hypertension. In stage 3, linear atelectasis and ibrotic changes are seen, as well as gradual clearing of areas of abnormal attenuation. In chronic stages, air trapping, ibrotic changes, triangular opacities, pulmonary architectural distortion, decreased bronchial diameters, bronchiectasis, bronchial wall thickening, tracheomegaly, tracheomalacia, enlarged pulmonary arteries, right ventricular enlargement, and pulmonary edema are seen. Differential diagnosis includes chronic lung disease, persistent pulmonary hypertension of the newborn, and Wilson-Mikity syndrome. Wilson-Mikity syndrome is seen in children between 1 and 2 months of age. History may include preterm delivery and low birth weight but typically no

history of high-pressure ventilation or high-concentration oxygen. Imaging is normal in the irst week but later similar to BPD, with hyperinlation, stranding, streaky iniltrates, and cystic changes. These changes may persist for a few months to years.

CONCLUSION CT and MRI are valuable in the evaluation of several pediatric thoracic abnormalities. CT is highly sensitive in the evaluation of chest abnormalities and is ideally suited for children owing to rapid acquisition times. The radiation dose should be kept as low as possible by performing only justiiable studies and optimizing the protocols. MRI is used as a problem-solving tool in the evaluation of several cardiovascular, mediastinal, and pleural abnormalities.

REFERENCES 1. Ackman JB, Wu CC: MRI of the thymus. AJR Am J Roentgenol 197(1):W15–W20, 2011. 2. Adzick NS, Harrison MR, Crombleholme TM, et al: Fetal lung lesions: Management and outcome. Am J Obstet Gynecol 179(4):884–889, 1998. 3. Adzick NS, Harrison MR, Glick PL, et al: Fetal cystic adenomatoid malformation: Prenatal diagnosis and natural history. J Pediatr Surg 20(5):483–488, 1985. 4. Agrons GA, Rosado-de-Christenson ML, Kirejczyk WM, et al: Pulmonary inlammatory pseudotumor: Radiologic features. Radiology 206(2):511–518, 1998. 5. Ahmed M, Jacobi V, Vogl TJ: Multislice CT and CT angiography for non-invasive evaluation of bronchopulmonary sequestration. Eur Radiol 14(11):2141–2143, 2004. 6. Alsenaidi K, Gurofsky R, Karamlou T, et al: Management and outcomes of double aortic arch in 81 patients. Pediatrics 118(5):e1336–e1341, 2006. 7. Araki T, Sholl LM, Gerbaudo VH, et al: Intrathymic cyst: Clinical and radiological features in surgically resected cases. Clin Radiol 69(7):732– 738, 2014. 8. Ardito JM, Ossoff RH, Tucker GF, Jr, et al: Innominate artery compression of the trachea in infants with relex apnea. Ann Otol Rhinol Laryngol 89(5 Pt 1):401–405, 1980.

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172. Weinberg PM: Aortic arch anomalies. J Cardiovasc Magn Reson 8(4):633–643, 2006. 173. Weisbrod GL, Chamberlain DW, Tao LC: Pulmonary blastoma, report of three cases and a review of the literature. Can Assoc Radiol J 39(2):130–136, 1988. 174. Wells TR, Gwinn JL, Landing BH, et al: Reconsideration of the anatomy of sling left pulmonary artery: The association of one form with bridging bronchus and imperforate anus. Anatomic and diagnostic aspects. J Pediatr Surg 23(10):892–898, 1988. 175. White RI, Pollak JS: Pulmonary arteriovenous malformations: Diagnosis with three-dimensional helical CT—A breakthrough without contrast media. Radiology 191(3):613–614, 1994. 176. Wick MR, Ritter JH, Humphrey PA: Sarcomatoid carcinomas of the lung: A clinicopathologic review. Am J Clin Pathol 108(1):40–53, 1997. 177. Wielpütz MO, Eichinger M, Puderbach M: Magnetic resonance imaging of cysti ibrosis lung disease. J Thorac Imaging 28(3):151–159, 2013. 178. Williams AJ, Schuster SR: Bronchial atresia associated with a bronchogenic cyst. Evidence of early appearance of atretic segments. Chest 87(3):396–398, 1985. 179. Wilson RD, Hedrick HL, Liechty KW, et al: Cystic adenomatoid malformation of the lung: Review of genetics, prenatal diagnosis, and in utero treatment. Am J Med Genet A 140(2):151–155, 2006. 180. Winters WD, Effmann EL: Congenital masses of the lung: Prenatal and postnatal imaging evaluation. J Thorac Imaging 16(4):196–206, 2001. 181. Wootton-Gorges SL, Stein-Wexler R, Walton JW, et al: Comparison of computed tomography and chest radiography in the detection of rib fractures in abused infants. Child Abuse Negl 32(6):659–663, 2008. 182. Yano Y, Mori M, Kagami S, et al: Inlammatory pseudotumor of the lung with rapid growth. Intern Med 48(15):1279–1282, 2009. 183. Yasufuku M, Maeda K, Takano Y: Thymopharyngeal duct cyst: An unusual cause of respiratory compromise. Pediatr Surg Int 25(9):807– 809, 2009. 184. Yi E, Aubry MC: Pulmonary pseudoneoplasms. Arch Pathol Lab Med 134(3):417–426, 2010.

42 Biliary Tract and Gallbladder Jae Hoon Lim, Kyoung Won Kim, and Dong-il Choi

BILIARY TRACT NORMAL ANATOMY AND VARIANTS On high-resolution computed tomography (CT), normal intrahepatic bile ducts (IHDs) appear as linear water-density structures accompanying the portal vein branches.177 Normal IHDs measure less than 3 mm. They appear to be randomly scattered throughout the liver but are conluent toward the hilum. The IHDs from each lobe unite to form the right and left main hepatic ducts, which are located anterior to the portal veins (Fig. 42-1). Periportal lymphedema can mimic a dilated IHD but shows a low-density area completely surrounding the portal vein.306 A common anomaly is an aberrant IHD that drains a circumscribed portion of the liver, such as an anterior or posterior segment right lobe duct that drains into the left rather than the right main hepatic duct. Surgical dificulties may arise when the cystic duct enters the right main hepatic duct before joining the left main hepatic duct. The right and left main hepatic ducts unite in the hilum to form the common hepatic duct (CHD). The CHD usually courses along a 45-degree oblique plane with reference to the midline sagittal plane, which lies to the right and lateral to the proper hepatic artery. The right hepatic artery typically branches off the proper hepatic artery and passes between the CHD and the main portal vein in about 80% of subjects.342 The common bile duct (CBD) forms when the cystic duct joins the CHD. This union occurs at varying levels, from high in the porta hepatis to near the ampulla of Vater. Because the union is usually not demonstrated on CT, the term common duct is used when the CHD and CBD cannot be differentiated. Duplications of the CBD and cystic duct are rarely observed. On CT the CHD usually measures 3 to 6 mm in short-axis diameter, and the CBD measures up to 8 mm.12 The diameter should be measured in the short axis because the duct often courses obliquely through the transverse image.96 In postcholecystectomy patients and some older adults, the CBD may measure up to 10 mm without obstruction.12 The wall of the CHD and CBD can normally be demonstrated and measures less than 1.5 mm.298 The wall may enhance normally and be brighter than the adjacent pancreas on contrastenhanced CT. The CBD enters the pancreas and typically lies along the posterior and lateral aspect of the pancreatic head. The distal CBD and main pancreatic duct come into contact on the medial side of the descending part of the duodenum. The two ducts pass separately through the wall of the duodenum and unite to form a short dilated tube—the ampulla of Vater. The sphincter of Oddi is the circular muscle complex around the CBD, pancreatic duct, and ampulla of Vater; it consists of the sphincter choledochus, sphincter pancreaticus, and sphincter ampullae. On endoscopic retrograde cholangiopancrea-

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tography (ERCP), the ampullary segment is usually not visualized because of the contraction of the sphincter of Oddi (Fig. 42-2). The ampulla of Vater is also responsible for the potential relux of pancreatic juice into the CBD.

CONGENITAL BILIARY ANOMALIES Biliary Atresia In biliary atresia, ultrasonography (US), CT, and a DISIDA (diisopropyl iminodiacetic acid) scan are the initial imaging studies to evaluate the biliary tree. In more than 10% of patients with biliary atresia, other anomalies are present, such as polysplenia, bilateral bilobed lungs, azygos continuation of the inferior vena cava, intestinal malrotation, and situs inversus.76 CT can identify the development of cirrhosis, varices, splenomegaly, and ascites and plays an important role in the evaluation of such patients before liver transplantation.

Anomalous Pancreaticobiliary Ductal Junction Anomalous pancreaticobiliary ductal junction is an uncommon congenital anomaly in which the main pancreatic duct and CBD are joined outside the duodenal wall and form a long common channel (usually >15 mm).181,322 Although this anomaly is found in almost all patients with congenital choledochal cyst, it is also observed in patients without choledochal cyst.181 Because an anomalous pancreaticobiliary ductal junction is frequently associated with cholangiocarcinoma, early diagnosis is important.181 ERCP is the most reliable method for detecting anomalous pancreaticobiliary ductal junction, but it is an invasive procedure (Fig. 42-3A). Recently magnetic resonance (MR) cholangiopancreatography (MRCP) and multidetector CT (MDCT) with multiplanar reconstruction of images have been used to diagnose this anomaly (see Fig. 42-3B and C).146,237

Choledochal Cyst Choledochal cyst involves congenital cystic dilatation of any portion of the extrahepatic bile ducts, most commonly the main portion of the CBD.70,80,108,187,357 It is classiied based on the spectrum of morphologic changes in the bile ducts. The most common classiication scheme is the Todani modiication of the Alonso-Lej classiication326: Type I: single cystic dilatation of the CBD, CHD, or both (80%-90% of cases) (Fig. 42-4) Type II: true diverticulum of the CBD (3%) Type III: choledochocele (5%) Type IV: any combination of cysts, which may include intrahepatic cystic dilatation (10%). Type IV-A involves multiple cysts of the common duct and IHDs, and type IV-B involves multiple cysts of the common duct. Type V: cystic dilatation of only the IHDs—so-called Caroli’s disease (rare)

CHAPTER 42

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B FIG 42-1 A, High-resolution CT shows normal intrahepatic bile ducts (IHDs) (arrows) as linear water-density structures accompanying the portal vein branches. B, T1-weighted MRI after administration of gadobenate dimeglumine demonstrates IHDs (arrows) with biliary excretion of contrast material located anterior to the portal veins.

detecting cystic dilatation of the bile duct on cross-sectional imaging. CT and magnetic resonance imaging (MRI) can make the diagnosis if direct communication with the cyst and the biliary tree is demonstrated (see Figs. 42-3 and 42-4). Cholangiography can conirm the diagnosis. Mild secondary dilatation of IHDs, stones, or sludge may be found as well (Fig. 42-5). Complications of choledochal cysts in adults include rupture with bile peritonitis, stone formation, cholangitis, hemorrhage, portal vein thrombosis, biliary cirrhosis, liver abscess, pancreatitis, and cholangiocarcinoma.108,284 An increased incidence (4%-28%) of malignancy involving the hepatobiliary system has been reported in patients with choledochal cysts, compared with normal subjects.188,325-327,354 Malignancy developing in patients with choledochal cyst may be caused by chronic mucosal irritation; it usually occurs in the choledochal cyst but can develop anywhere in the biliary tree, including the gallbladder354 (Fig. 42-6). Cholangiocarcinoma arising in a choledochal cyst appears as a soft tissue–density mass or irregular thickening of the cyst wall. The principal management of choledochal cysts is surgery, with excision of all cyst tissue and reconstruction of continuity between the liver and the gut.284,325 FIG 42-2 Normal ERCP image shows the bile ducts, gallbladder, and main pancreatic duct. The distal part of the common bile duct (arrow) is not seen owing to contraction of the sphincter of Oddi.

Among these ive types, types III and V are not cystic dilatation of the CBD and thus are not considered true choledochal cysts. The cause of this condition is not clear, but it may be multifactorial. It has been suggested that choledochal cyst, biliary atresia, and neonatal hepatitis are part of the same spectrum of disease.194 This condition is also associated with an increased incidence of gallbladder anomalies and congenital hepatic ibrosis. It may result from an anomalous pancreaticobiliary ductal junction, with free relux of pancreatic enzymes into the CBD. Choledochal cysts are more common in females. Although they can present from birth to old age, about 60% of choledochal cysts are found before adolescence. Newborns and infants present with obstructive jaundice; older children and adults may have right upper quadrant pain, mass, and intermittent jaundice. The diagnosis is easily made by

Choledochocele Choledochocele is a rare anatomic anomaly of unknown cause. It is a protrusion of a dilated intramural segment of the distal CBD into the duodenum, analogous to a ureterocele.61,296,361 On CT a round waterdensity structure is found in or medial to the pancreatic head or occasionally within the lumen of the duodenum. Differential diagnostic considerations include an intraluminal duodenal diverticulum, small pseudocyst, duodenal duplication cyst, or small cystic neoplasm of the pancreas. Cholangiography shows smooth saccular dilatation of the intramural segment of the CBD (Fig. 42-7). Stones and sludge are common, and patients sometimes have episodes of biliary colic, intermittent jaundice, and pancreatitis as well.61,296

Caroli’s Disease Caroli’s disease is also known as communicating cavernous ectasia of the IHDs. The uncommon pure form of this entity involves congenital saccular dilatation of only the IHDs. The more common classic form consists of saccular dilatation of the IHDs with congenital hepatic

C

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FIG 42-3 Anomalous pancreaticobiliary ductal junction. A, ERCP shows a long common channel measuring more than 15 mm (arrowheads). B, MRCP demonstrates an anomalous pancreaticobiliary ductal junction (arrow) and a choledochal cyst (C). Note the long common channel (arrowheads). C, Coronal MDCT with multiplanar reconstruction demonstrates a long common channel (arrowheads) and choledochal cyst (C).

C

C C

FIG 42-4 Choledochal cyst (C). MRCP demonstrates a markedly dilated common bile duct (choledochal cyst) and aberrant insertion of the common duct into the pancreatic duct (arrow).

FIG 42-5 Choledochal cyst (C) with a small stone (arrow) on MRCP.

CHAPTER 42

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C

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FIG 42-6 Gallbladder cancer associated with choledochal cyst (C). A, MRCP shows a lobulated illing-defect lesion (arrows) in the gallbladder. B, T2-weighted transverse MRI demonstrates gallbladder cancer (arrows).

C

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C FIG 42-7 Choledochocele. A, MRCP shows a choledochal cyst (C) and choledochocele (arrow). T2-weighted transverse MRI (B) and MDCT (C) show a small cholangiocarcinoma (arrow) within the choledochocele.

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FIG 42-8 Caroli’s disease. MDCT shows cystic dilatation of the intra-

FIG 42-9 Three small stones in the gallbladder and one stone in the

hepatic bile ducts with stones (white arrows). The black arrow indicates the so-called central dot sign.

common bile duct, which migrated from the gallbladder.

ibrosis.56,234,314 The common association of congenital CBD dilatation suggests that Caroli’s disease may be part of the spectrum of choledochal cyst. In addition this disease is frequently associated with renal tubular ectasia and other renal cystic disease.234 Clinically Caroli’s disease usually manifests in adulthood; however, it can be observed in newborns and infants. Adult patients generally present with recurrent attacks of cholangitis. Infants and children may present with hematemesis caused by hepatic ibrosis and portal hypertension.77,158,234 On CT the saccular dilatation of the IHDs may mimic multiple hepatic cysts. The cystic areas of Caroli’s disease can be shown to communicate directly with the IHDs.12 The distribution of cystic dilatation is often segmental (Fig. 42-8). CT may also show tiny dots with strong contrast enhancement within dilated IHDs—the so-called central dot sign. These dots represent the enhancing portal veins.56 Caroli’s disease is best demonstrated by cholangiography, which shows saccular dilatations of the IHDs. Complications of Caroli’s disease include stone formation, cholangitis, hepatic abscess, hepatic amyloidosis, pancreatitis, and biliary malignancy.133,222

PATHOLOGIC CONDITIONS Choledocholithiasis (Bile Duct Stones) Stones in the extrahepatic duct may originate from the gallbladder or primarily from within the bile ducts. Primary stones are formed primarily in the extrahepatic bile ducts. Clearly, stones in the extrahepatic ducts in patients with cholecystectomy or congenital absence of the gallbladder are primary.27 Extrahepatic duct stones that originate in the gallbladder and later pass through the cystic duct into the CBD are called secondary stones.27 In Western countries, stones in the CBD are composed of cholesterol in about 80% of cases and calcium bilirubinate in 20%. Cholesterol stones arise exclusively in the gallbladder; these stones contain more than 50% crystalline cholesterol monohydrate.6 Calcium bilirubinate stones are composed predominantly of bilirubin calcium salt; these fragile stones are also called pigment stones.6 About 95% of patients with choledocholithiasis in Western countries also have gallbladder stones228 (Fig. 42-9); when they do not, the gallbladder may show acute or chronic inlammatory changes, suggesting that it previously contained stones27 (Fig. 42-10).

FIG 42-10 A small stone (arrow) in the common bile duct originated in the gallbladder. The wall of the gallbladder is thickened and enhanced, suggesting acute cholecystitis.

In Asia, pigment stones account for more than 50% of stones, and they are formed primarily in the bile ducts6 (Fig. 42-11). Unlike cholesterol stones, pigment stones can crumble or crush easily.6 Some stones are very friable or muddy, like earth, loating in the bile as debris. The formation of pigment stones is related to a high prevalence of recurrent pyogenic cholangitis. Infection of the biliary tract, such as with Escherichia coli, Clonorchis sinensis, Opisthorchis viverrini, or Ascaris lumbricoides, increases the likelihood of pigment stone formation by increasing the concentration of insoluble calcium salts of unconjugated bilirubin.239

Intrahepatic Stones. Intrahepatic biliary stones, which are formed primarily within the IHDs, are rare in Western countries.183 These stones occur in patients with underlying biliary anomalies such as Caroli’s disease, biliary atresia, or cystic ibrosis or previous biliary surgery.92 In some parts of Asia, intrahepatic stones are common in patients with recurrent pyogenic cholangitis. The stones are found mostly in the large-caliber ducts, such as the left hepatic lobe (Fig. 42-12) or the posterior segment of the right hepatic lobe. The stones

CHAPTER 42 migrate downward to the CBD or reside in the liver when there is a stricture. The bile duct wall shows chronic proliferative cholangitis, suppurative cholangitis, and chronic granulomatous cholangitis, resulting in severe ibrosis and inlammatory cell iniltration.183

Natural History. The natural history of choledocholithiasis is unpredictable. Small stones may pass spontaneously into the duodenum without causing symptoms. Clinical and autopsy series suggest that nearly half of stones do not produce clinical manifestations such as cholangitis or jaundice.359 Spontaneous resolution of jaundice occurs as the stones pass through the duodenal papilla or if the stones loat back up to the proximal bile duct away from the narrow distal end.27 Passage of a large stone through the narrow duodenal papilla can induce papillitis or papillary stenosis and incomplete bile duct obstruction254 (Fig. 42-13). Stones that do not pass and reside in the bile duct may induce obstructive jaundice and cholangitis or pancreatitis (Fig. 42-14). When

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a stone obstructs the bile duct in the absence of infected bile, asymptomatic luctuating jaundice often ensues. When a stone obstructs the CBD and the bile becomes infected, acute suppurative cholangitis ensues (Fig. 42-15). The classic triad of symptoms is fever with chills, pain, and jaundice. In patients with recurrent pyogenic cholangitis, stones are continually formed in the bile ducts and repeatedly pass through the ampulla of Vater and duodenal papillary oriice; this can cause papillary stenosis, presenting with recurrent bile duct obstruction and cholangitis.272 Typically patients experience one or two attacks of acute suppurative cholangitis a year.

Imaging Findings. The detectability of a bile duct stone on CT depends on the calcium content. Although many stones are cholesterol stones, some have suficient bilirubinate and calcium to exhibit high attenuation on CT images6 (Fig. 42-16). About 20% of stones are homogeneously calciied and easily seen; in others the calcium content is variable.14 Depending on the composition, stones may show soft tissue attenuation, near-water attenuation, or fat or air attenuation, with peripheral calciication around the stone.14 Precontrast CT is

FIG 42-11 Multiple stones formed in the common bile duct. There is a tight stricture at the conluence of the bile ducts (arrow). This patient underwent cholecystectomy 10 years ago, so the stones formed in the common bile duct.

A

FIG 42-12 Multiple calciied intrahepatic stones formed in the liver in a patient with recurrent pyogenic cholangitis.

B FIG 42-13 Duodenal papillitis due to a passed stone. The duodenal papilla is swollen (arrow) on CT (A) and cholangiogram (B), and the bile ducts are dilated.

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FIG 42-14 Gallstone pancreatitis. The pancreas is enlarged and there is a peripancreatic luid collection. The common bile duct (arrow) is dilated and the wall is thick. Note the tiny stones in the gallbladder and the thickened gallbladder wall.

necessary to visualize calciied stones because postcontrast CT masks them264 (Fig. 42-17). Some stones with mixed composition are isoattenuating to bile or adjacent soft tissue and are therefore dificult to detect on CT (Fig. 42-18). Pure cholesterol stones are rare but exhibit low attenuation resembling that of soft tissue (Fig. 42-19) or bile (Fig. 42-20). Stones containing fat or air can be detected because of the difference in attenuation from bile (Fig. 42-21). For more accurate detection of intrahepatic ductal stones, thin section with narrow collimation (1 mm), whereas in cholangitis the bile duct wall is thinner than 1 mm. Furthermore, the involved segment of the bile duct is narrowed or obliterated in cholangiocarcinoma but normal or dilated in cholangitis. Intraductal-growing type. The intraductal tumor may be polypoid, sessile, or supericially spreading along the lumen.174,210,217,218 There may also be multiple discrete tumors (papillary cholangiocarcinomatosis) along the inner surface of the bile ducts. Usually the tumor is limited to the mucosa and invades the wall and surrounding tissue in the very late phase.210,217,218 An intraductal papillary cholangiocarcinoma is friable and sloughs easily by touching or rubbing at the time of surgery, or it may slough spontaneously and occlude the bile ducts, simulating a bile duct stone214 (Fig. 42-85). The bile ducts are dilated and incompletely obstructed by the tumor itself or by viscous mucin.

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B FIG 42-84 Periductal-iniltrating cholangiocarcinoma. MR cholangiogram (A) and source image (B) show segmental narrowing of the proximal extrahepatic duct (arrows in B).

A B

C FIG 42-85 Intraductal-growing cholangiocarcinoma of the extrahepatic duct. Axial (A) and coronal (B) CT images show a large castlike intraductal tumor (arrows). ERCP (C) shows a large intraductal tumor with an irregular papillary surface.

CHAPTER 42 On imaging, the bile ducts proximal to the tumor are dilated; the degree of dilatation depends on the degree of obstruction and the amount of mucin. The intraductal tumor is depicted as a sessile or castlike mass on sonography, CT, or MR cholangiography (see Fig. 42-85).174,214,219,221 The tumor is usually small and lat but may occasionally be large. The tumor tends to spread supericially along the lumen for a variable length and sometimes implants along the inner surface of the bile ducts, resulting in multiple discrete tumors.179,210,218,220 Although an intraductal tumor may be large, elongated, or castlike in shape, the tumor-harboring bile duct is typically not completely obstructed; bile low is maintained through the space between the tumor surface and the bile duct wall (see Fig. 42-85).214,221 Cholangiography shows a serrated or velvety surface of the intraductal tumor and a smooth normal bile duct wall (see Fig. 42-85).221 Early bile duct carcinoma, which is deined as carcinoma limited to the mucosa or ibromuscular layer of the bile duct, may have an appearance similar to that of intraductal-growing tumor. On CT the bile ducts harboring the tumor mass are clearly delineated as a sharply deined outer margin or a thin enhancing ring that may be more densely enhanced than the tumor mass.212 The thickened ibromuscular layer of the tumor-bearing bile duct wall seems to be responsible for this appearance. The periductal fat is clear and not iniltrated. If

Biliary Tract and Gallbladder

the tumor is resected, the patient has an excellent prognosis; cure rates range from 80% to 100%.38,212

Intraductal papillary mucinous tumors of the bile ducts. Some papillary tumors of the bile ducts produce a large amount of mucin122,201,219,353 and the mucin may impede the low of bile, resulting in obstructive jaundice. Endoscopy may show mucin protruding from the patulous oriice of the duodenal papilla. This tumor has a striking similarity to an intraductal papillary tumor of the pancreas in terms of its histopathology, production of excessive mucin, and pathophysiology.170,271 The bile ducts show severe dilatation; bile ducts both proximal and distal to the tumor are dilated because the viscous mucin does not easily pass the papilla of Vater. On imaging the tumor may appear as a nodular or castlike mass illing the bile ducts for a varying length (Fig. 42-86). Some intrahepatic papillary mucinous tumors produce aneurysmlike cystic dilatation of the bile ducts,122,210,213,219,360 which harbor multiple fungating intraductal papillary tumors (Fig. 42-87). Some of the involved bile ducts dilate cystically, and others dilate diffusely and proportionally. Rarely a biliary intraductal papillary neoplasm presents only as dilatation of the lobar or segmental bile ducts, with no mass visible on imaging or evident on pathology studies.211 The bile ducts are dilated

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C FIG 42-86 A and B, Intraductal papillary mucinous adenocarcinoma (arrow) in the dilated intrahepatic ducts. The extrahepatic ducts are markedly dilated with mucin. C, Cholangiogram shows a large amount of mucin in the extrahepatic duct (arrows).

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FIG 42-87 Cystic intraductal papillary mucinous adenocarcinoma containing innumerable small papillary tumors. Note dilated intrahepatic bile ducts and communication with the large cystic tumor.

and lined by papillary mucinous epithelial cells with a varying degree of dysplasia and malignant change. Because of abundant mucin production by the lining cells, the bile ducts are markedly dilated and the involved hepatic parenchyma becomes markedly atrophic. In severe cases the bile ducts are crowded and the hepatic parenchyma is virtually absent (Fig. 42-88).

Imaging techniques for diagnosis and staging of cholangiocarcinoma. Surgical resection with complete removal of all cancerous tissue offers patients the only chance for cure or long-term survival. Advances in surgical techniques and devices have improved the results of aggressive surgery for cholangiocarcinoma.152,203,207,229,230,257 Advanced cholangiocarcinoma that was once considered inoperable has now become resectable. The criteria for tumor resectability are constantly changing. Accurate preoperative staging and in-depth knowledge of the anatomy of the liver and bile duct are prerequisites for curative resection. With improved imaging techniques, detailed information about the pathologic anatomy is now available for preoperative planning. In the preoperative assessment of an intrahepatic cholangiocarcinoma, the primary concern is whether an apparently tumor-free segment of the right and left lobe is involved, thus permitting the obviously involved segment to be excised.50,261 For hilar cholangiocarcinoma the preoperative evaluation must address the extent of tumor along the bile ducts (Fig. 42-89). In periductal-type hilar or extrahepatic cholangiocarcinoma, information about the extent of tumor along the bile ducts (including the cystic duct), direct invasion into the adjacent arteries and portal vein, lymph node metastasis, and direct invasion of or metastasis to the liver is essential (Figs. 42-90 and 42-91). In an intraductal tumor, which frequently spreads supericially along the mucosal surface, the true extent of the tumor may be dificult to determine even with a high-quality cholangiogram (Fig. 42-92). CT or MRI can demonstrate thickening of the bile ducts, but the thickening might be caused by chronic obstruction without tumor involvement. Therefore cholangioscopy and a biopsy may be necessary before surgical resection.201 MDCT has excellent image quality, providing valuable information about the pathologic anatomy of the biliary tree, other abdominal organs, and peritoneal cavity. The use of advanced image processing, including maximum intensity projection and multiplanar reconstruction (especially coronal or sagittal reformatted images), allows superior

FIG 42-88 Intraductal papillary mucinous adenoma with tumor cells lining the bile ducts but no visible mass formation. CT shows severely dilated left intrahepatic bile ducts without a visible mass. Liver parenchyma is virtually absent owing to severe pressure atrophy. (From Lim JH, Jang KT, Choi D: Biliary intraductal papillary-mucinous neoplasm manifesting only as dilatation of the hepatic lobar or segmental bile ducts: Imaging features in six patients. AJR Am J Roentgenol 191:778– 782, 2008.)

three-dimensional visualization of the biliary tree and vascular structures.3,37,44,147,168,358 Even without the use of a contrast agent, such images are considered comparable to conventional cholangiography. MR cholangiography is accurate in identifying the presence and level of a cholangiocarcinoma. MR cholangiography in conjunction with conventional abdominal MRI and MR angiography yields a comprehensive examination that permits the diagnosis and staging of cholangiocarcinoma. An MR cholangiogram provides information about the extent of tumor along the bile duct, and MRI and MR angiography provide information about lymph node metastasis and vessel involvement.44,68,225,235,351 Cholangiography, including endoscopic retrograde cholangiography and percutaneous cholangiography via a drainage catheter, can be used to assess the extent of the tumor, but the depth of bile duct invasion cannot be determined (see Fig. 42-92). In addition the procedure is invasive, with a major complication rate of 1.4% to 5%, and technical failure to visualize the bile ducts or inadequate visualization occurs in about 10% to 20% of all attempts.104 Also, when the bile duct is completely obstructed, the extent of cancer cannot be evaluated in the duct proximal to the obstruction. Fluorodeoxyglucose positron emission tomography (FDG PET) is valuable for evaluating suspicious lesions (Figs. 42-93 to 42-95) and detecting unsuspected distant metastases in patients with peripheral cholangiocarcinoma that might preclude surgical therapy and result in a change in their oncologic management.6,179,279 In addition, it is possible to evaluate cholangiocarcinoma in the setting of sclerosing cholangitis.6 However, FDG PET has a high false-negative rate for the detection of periductal-iniltrating cholangiocarcinoma6,179,279 (Fig. 42-96). Even though each imaging modality has a role, the use of several modalities may be necessary for accurate diagnosis and staging.44,68,202,291 Other malignant tumors of the bile ducts. Hepatocellular carcinoma may present with a biliary intraductal tumor consisting of

CHAPTER 42

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FIG 42-89 Hilar cholangiocarcinoma, Bismuth type IV. A and B, CT shows concentric thickening of the wall of the right and left hepatic ducts and common hepatic duct. Adjacent periductal fat and vessels are intact. C and D, Contrast-enhanced MRIs show concentric thickening of the bile duct wall and enhancement. There is no evidence of tumor extension out of the bile duct.

FIG 42-90 Periductal-iniltrating cholangiocarcinoma producing circumferential thickening of the bile duct wall (arrows). Note that the tumor has invaded the portal vein and right and left hepatic arteries.

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D FIG 42-91 Periductal-iniltrating hilar cholangiocarcinoma, Bismuth type IIIA. A to C, CT images show concentric thickening of the right hepatic duct, common hepatic duct, and cystic duct (short arrows) and the common bile duct. Note the metastatic lymph node (long arrow in B) invading the replaced right hepatic artery from the superior mesenteric artery. The common hepatic artery and portal vein have not been invaded. D, Cholangiogram shows a cholangiocarcinoma of the common hepatic duct and right hepatic duct (arrow).

A

B FIG 42-92 Hilar cholangiocarcinoma, Bismuth type II. A, CT shows concentric thickening of the wall of the common hepatic duct and right and left hepatic ducts (arrow). B, ERCP shows normal right and left hepatic ducts (arrows) with tumor limited to the common hepatic duct.

CHAPTER 42

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B FIG 42-93 Carcinoma of the ampulla of Vater. A, CT shows a small suspicious mass at the duodenal papilla (arrow). The distal common bile duct is dilated. B, FDG PET shows a lesion at the ampulla of Vater (arrow).

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B FIG 42-94 Cholangiocarcinoma of the distal common bile duct. A, CT shows a nodular mass (arrow) in the bile duct. B, FDG PET shows increased uptake (arrow) indicating cancer.

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B FIG 42-95 Recurrence of cholangiocarcinoma. A, CT 2 years after surgery for hilar cholangiocarcinoma shows a suspicious nodule at the resection margin (arrow). B, FDG PET shows intense uptake at the resection margin (arrow) indicating recurrent cancer.

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C FIG 42-96 Cholangiocarcinoma. A, CT shows a small nodule in the dilated common bile duct (arrow). B, Cholangiogram shows complete obstruction of the common bile duct (arrow). C, FDG PET discloses no lesion.

either a polypoid or a pedunculated mass, resulting in obstructive jaundice.335,338 A hepatic parenchymal tumor may invade the bile ducts and grow within them like a thrombus. Rarely hepatocellular carcinoma may arise primarily within the bile ducts, with no tumor in the adjacent liver parenchyma; the bile duct wall is intact in this type of tumor. Like ordinary parenchymal hepatocellular carcinoma, intraductal hepatocellular carcinoma is well enhanced on contrast-enhanced CT or MRI (Fig. 42-97). Underlying liver cirrhosis may be helpful in differentiating hepatocellular carcinoma from cholangiocarcinoma. Embryonal rhabdomyosarcoma is the most common malignant tumor in the pediatric population, occurring mainly in infants and preschool-aged children. Most of these tumors arise in the CBD and present as polypoid masses obstructing the bile duct lumen.74,315 In adults, lymphoma, leiomyosarcoma, and carcinoid tumor may occur. Leukemic involvement of the biliary tree may produce segmental thickening of the bile duct wall and obliteration of the lumen, mimicking hilar cholangiocarcinoma45 (Fig. 42-98). Metastatic tumors from gastric and colon cancer may produce diffuse or segmental thickening of the extrahepatic bile duct wall (Figs. 42-99 and 42-100). Periductal lymph node metastasis produces bile duct compression and invasion and causes bile duct obstruction.

FIG 42-97 Hepatocellular carcinoma in the common hepatic duct. Contrast-enhanced CT shows an enhancing nodular mass illing the common hepatic duct like a thrombus (arrow). The proximal bile ducts are dilated.

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B

A

FIG 42-98 Leukemic iniltration along the common hepatic duct. A, CT shows severe wall thickening (arrows) around the biliary drainage catheter. B, ERCP shows severe segmental thickening of the common hepatic duct and dilated intrahepatic duct.

FIG 42-99 Extrahepatic duct metastasis with disseminated metastatic tumors in a patient with colon cancer. Note the tumor mass inside the bile duct (arrow).

Tumors of the Ampulla of Vater and Duodenal Papilla. The ampulla of Vater and duodenal papilla are small continuous structures at the distal end of the CBD. The ampulla of Vater is within the wall of the duodenum and the papilla is in the lumen of the duodenum. A tumor may arise from either one. An ampullary tumor is deined as a tumor conined to the ampulla without signiicant extension into the duodenum, whereas a tumor of the major papilla involves primarily the duodenal mucosa at the papilla. An ampullary tumor can easily involve the duodenal papilla and vice versa. Differentiation is important because a benign tumor of the duodenal papilla can be treated by endoscopic resection. Villous adenoma is the most common tumor arising from the duodenal papilla. Not infrequently, adenocarcinoma may develop from a preexisting villous adenoma of the papilla.157 The adenocarcinoma may arise from the ampulla of Vater (Fig. 42-101) or the duodenal

FIG 42-100 Extrahepatic duct metastasis in a patient with rectal cancer. The bile duct wall is concentrically thickened, with intense mucosal enhancement (arrow).

papilla (Fig. 42-102) and produce biliary obstruction. The tumor is depicted by CT or MR cholangiography as a mass at the distal end of the CBD or in the duodenal lumen.29,139,166 Although the bile ducts are dilated secondary to obstruction, the main pancreatic duct is usually not dilated because of the presence of the accessory pancreatic duct. A small intraampullary mass is usually not visualized on duodenal endoscopy, because the mass is inside the ampulla of Vater. Large ampullary tumors with duodenal papillary bulging are more easily identiied with endoscopy and imaging such as CT and MR cholangiography. Likewise, tumors arising from the distal CBD and the head of the pancreas may be dificult to differentiate.166 However, owing to recent progress in MDCT, MR cholangiography, and endoscopic sonography, differentiation of these tumors has been simpliied. Duodenal endoscopy is a helpful adjunct in the diagnosis of tumors arising from the duodenal papilla and ampulla of Vater region.

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B

C FIG 42-101 Carcinoma of the ampulla of Vater. Axial (A) and coronal (B) CT and MRCP (C) show a round mass at the ampulla of Vater (arrow) resulting in obstruction of the bile ducts and pancreatic duct.

A

B FIG 42-102 Adenocarcinoma of the duodenal papilla. A large lobulated mass (arrows) is evident within the duodenum on CT (A) and MRCP (B), causing bile duct obstruction.

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GALLBLADDER NORMAL ANATOMY The gallbladder is a blind pouch lying along the undersurface of the liver. The gallbladder fossa is located in the plane of the interlobar issure, which lies between the right and left hepatic lobes. On transverse CT images, the gallbladder is a rounded structure with a maximum diameter of less than 4 to 5 cm in the distended state.127 When contracted the gallbladder is a smaller tubular structure. Visualization of the gallbladder wall depends on the degree of gallbladder distention and the presence of abnormality. The normal gallbladder wall thickness ranges from 1 to 3.5 mm.311,312,343 On US, 3 mm might be a reasonable upper limit of normal. Enhancement of the gallbladder wall on CT and MRI is normal after the intravenous administration of contrast medium.321,343 The density of the gallbladder lumen is generally that of water (0-20 Hounsield units [HU]).127 After intravenous contrast administration, an increase in density is observed on CT. In general a small fraction of the contrast medium is excreted into the biliary tree. This amount is usually too small to be seen on plain ilms.321,332,333

FIG 42-103 Phrygian cap. Transverse MDCT shows a phrygian cap with a thickened wall (arrow) containing sandy stones.

CONGENITAL VARIANTS AND ANOMALIES Agenesis of the Gallbladder Gallbladder agenesis results from failure of development of the caudal division of the primitive hepatic diverticulum or from failure of vacuolization after the solid phase of embryonic development. Also, atresia or hypoplasia of the gallbladder represents aborted development of the organ.5,67,117 This malformation is reported in 0.013% to 0.155% of autopsy series, but the surgical incidence of gallbladder agenesis is approximately 0.02%.5,22 Nearly two thirds of adult patients with agenesis of the gallbladder have biliary tract symptoms, and gallstones in the extrahepatic bile duct are observed in 25% to 50% of these patients.16,82 Although US, CT, or MRI may suggest the diagnosis, preoperative diagnosis of gallbladder agenesis is dificult.125,126 This disorder is generally diagnosed during intraoperative cholangiography.

Duplication of the Gallbladder 113

Gallbladder duplication occurs in 0.025% of the population. This anomaly is caused by incomplete revacuolization of the primitive gallbladder, resulting in a persistent longitudinal septum. Each separate gallbladder cavity must have its own cystic duct. These duplicated cystic ducts may enter the common duct separately or unite before a common entrance.331 Most reported cases of gallbladder duplication include a clinical picture of cholecystitis with stones. A folded gallbladder, bilobed gallbladder, choledochal cyst, pericholecystic luid, gallbladder diverticulum, vascular band across the gallbladder, and focal adenomyomatosis can mimic a double gallbladder.99,110,258 Complications in double gallbladder include torsion, papilloma, carcinoma, common duct obstruction, and biliary cirrhosis. Triple and quadruple gallbladders have also been reported.99

Phrygian Cap The most common anomaly of the entire biliary tree is a septation in the distal fundus of the gallbladder, which results in the coniguration called a phrygian cap (Fig. 42-103). It occurs in 1% to 6% of the population.83 This deformity is characterized by a fold or septum of the gallbladder between the body and fundus. Two variations of this anomaly have been reported. In the retroserosal or concealed type, the mucosal fold projecting into the lumen may not be visible externally. In the serosal or visible type, the peritoneum follows the bend

FIG 42-104 Multiseptate gallbladder. The thickened wall of the fundal segment (arrow) may represent chronic segmental cholecystitis.

in the fundus and then relects on itself as the fundus overlies the body. This anomaly can be mistaken for stones or hyperplastic cholecystosis.83,99,110,258

Multiseptate Gallbladder Septations occur elsewhere in the gallbladder but are less common and may be multiple.243 The multiseptate gallbladder is a solitary gallbladder with multiple septa of various sizes internally.328 The gallbladder is usually normal in size and position, and the chambers communicate with one another by one or more oriices from the fundus to the cystic duct. These septations lead to stasis of bile and gallstones1 (Fig. 42-104). The differential diagnoses include desquamated gallbladder mucosa and hyperplastic cholecystosis.

Diverticula Gallbladder diverticula can occur anywhere in the gallbladder; they are usually single and can vary greatly in size.184 Congenital diverticula are true diverticula and contain all the muscle layers. In contrast the pseudodiverticula of adenomyomatosis have little or no smooth muscle in their walls.

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Wandering Gallbladder The gallbladder may have a long mesentery that allows it to lie in an abnormal location, such as the pelvis243—the so-called wandering or loating gallbladder. It may also wander in front of the spine or to the left of the abdomen and can rarely herniate through the foramen of Winslow into the lesser peritoneal sac. These wandering gallbladders may be prone to torsion or volvulus.

Ectopic Gallbladder The gallbladder can be located in various positions (Fig. 42-105). The intrahepatic gallbladder is completely surrounded by hepatic parenchyma and typically lies in a subcapsular location along the anteroinferior aspect of the right hepatic lobe. It may complicate the clinical diagnosis of acute cholecystitis because there are few peritoneal signs. With hypoplasia, aplasia, atrophy, or hypertrophy of one of the hepatic lobes, the gallbladder may be displaced or rotated abnormally to one side. In patients with cirrhosis and associated atrophy of the right hepatic lobe or chronic obstructive pulmonary disease, the gallbladder together with the colon is often interposed between the liver and the diaphragm.111,263 A suprahepatic gallbladder has been described, with hypoplasia of the right hepatic lobe and eventration of the diaphragm.39 Patients with disease in an ectopic gallbladder may present diagnostic challenges because their symptoms are atypical with regard to the location of pain.

Cholecystomegaly and Microgallbladder Enlargement of the gallbladder has been reported in patients with diabetes and after vagotomy. The gallbladder also becomes larger than normal during pregnancy, in patients with sickle hemoglobinopathy, and in extremely obese people.15,87,251,336 In patients with cystic ibrosis, the gallbladder is typically small, trabeculated, contracted, and poorly functioning.242,346 Microgallbladder often contains echogenic bile, sludge, and cholesterol gallstones.

PATHOLOGIC CONDITIONS When renal function is abnormal, hepatobiliary excretion of contrast agent may be pronounced, with increased density of the gallbladder lumen on CT and plain ilms.302,321 Abnormal density of the gallbladder

FIG 42-105 Ectopic gallbladder. Transverse MDCT shows the ectopic gallbladder (arrow) between the stomach and left hepatic lobe.

lumen on CT can occur in various pathologic conditions. Hemobilia can increase the density of bile toward that of blood (50-60 HU).190 Innumerable tiny stones may appear simply as increased bile density in the gallbladder lumen when the stones are too small to be identiied individually. However, the most common cause of increased bile density in the gallbladder lumen is cystic duct obstruction resulting from a stone or tumor. In acute and chronic cholecystitis, the density of the gallbladder lumen can be increased owing to inlammatory debris.332,333 Milk of calcium bile often makes a luid-luid level, with the denser calcium salt suspension layering dependently. It may have a density as high as 1000 HU.141 The cystic duct joining with the CHD forms the CBD at varying levels from high in the porta hepatis to near the ampulla of Vater (Fig. 42-106).

Gallstones Several factors affect the appearance of gallstones on CT, but the major determinant is composition: bile pigment, cholesterol, or calcium. Most gallstones are admixtures of these three elements, and their density depends on the amount of each element present. In general, calcium increases the density of the stone; up to 60% of gallstones attributed to calcium are dense on CT (Fig. 42-107). Mixed-composition stones with less calcium may have a density equal to that of bile, making them dificult to visualize on CT (Fig. 42-108). Pure cholesterol stones are rare but may have a lower density than bile (−100 HU in vitro).28,97 Also, the pattern in which calcium is distributed affects the appearance of gallstones. Whereas calcium bilirubinate stones may have a homogeneously dense appearance, mixed-composition stones may have a low-density cholesterol center and a dense peripheral rim of calcium, producing a laminated appearance with alternating layers of calcium or punctate foci of calcium scattered throughout (see Fig. 42-107). Gallstones may have central clefts in their matrix that contain gas consisting mostly of nitrogen, producing the so-called Mercedes-Benz, crow’s feet, or seagull sign. A gaseous cleft may contribute to the loating of gallstones, aiding in their detection on CT when they are isodense to bile (Fig. 42-109). It has been reported that CT was 78% sensitive prospectively and 94% sensitive retrospectively in the detection of gallstones.127 Again, the composition of the gallstone is the most important factor in the detection rate. Calciied gallstones that are hyperdense compared with bile are more readily detected than isodense mixed-composition stones. In addition the size, number, and shape of gallstones, as well as bile density and scanning technique, can affect the ability to detect gallstones on CT. On MRI, gallstones tend to have low signal intensity on both T1and T2-weighted images. T2-weighted sequences are considered superior to T1-weighted sequences, because gallstones are easily contrasted against the high signal intensity of the surrounding bile39 (Fig. 42-110). Although cholesterol gallstones usually have low signal intensity on T1-weighted images, pigment gallstones, seen as brown to black on cross section, tend to have high signal intensity, and the intensity ratio of gallstone to bile is signiicantly higher for pigment gallstones than for cholesterol gallstones329 (Fig. 42-111). Sometimes a high-signalintensity center is seen on T2-weighted images, which corresponds to a luid-illed cleft on cross section334 (Fig. 42-112). MRI should be carefully interpreted for the presence of gallstones in patients with pneumobilia, because the signal void from an air bubble can mimic a gallstone on T2-weighted images (Fig. 42-113). The differentiation of cholesterol and pigment gallstones was important when patients were treated with nonsurgical dissolution therapy, because the choice of the solvent and the success rate depended on the composition of the gallstones. In the era of laparoscopic

CHAPTER 42

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Biliary Tract and Gallbladder

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B

C FIG 42-106 MDCT of the gallbladder and cystic duct. A, Transverse scan shows the cystic duct (single arrow) and two gallstones (two arrows) in the gallbladder neck. B, Transverse scan 15 mm above A shows the common hepatic duct (arrow) and right bile duct (arrowheads). C, Coronal image shows the common bile duct (black arrow) and cystic duct (white arrows) with spiral folds.

cholecystectomy, however, the assessment of gallstone composition has become less important.

Acute Cholecystitis Acute cholecystitis is caused by obstruction of the cystic duct or gallbladder neck, resulting in inlammation of the gallbladder wall and increased intraluminal pressure.20 Although most patients present with right upper quadrant pain and tenderness, the diagnosis may be a challenge in the setting of severe advanced inlammation or in older patients or those with systemic diseases such as diabetes. The clinical signs and symptoms of acute cholecystitis are nonspeciic, and in 60% to 85% of patients evaluated for cholecystitis, the symptoms are found to result from other causes.276 The majority of cases of acute cholecystitis (≈90%) are caused by gallstones. The precipitating event for the development of acute calculous cholecystitis appears to be occlusion of the gallbladder neck or cystic duct by a gallstone. However, outlow obstruction does not always cause acute cholecystitis, and animal models in which the cystic duct was ligated or obliterated showed only shrinkage of the gallbladder, without the development of acute cholecystitis.293 Therefore mucosal ischemia or injury may be another contributing factor in the development of acute cholecystitis.308 US is generally the screening method of choice in a patient with suspected acute cholecystitis. CT is usually performed for evaluation

of suspected complications of acute cholecystitis such as gallbladder perforation (discussed later). However, CT may be used as an initial imaging modality if the cause of symptoms is unclear or if US indings are equivocal. The CT features of acute calculous cholecystitis include gallstones, thickening of the gallbladder wall, pericholecystic inlammatory change such as luid collection and fat stranding, highattenuation bile, blurring of the interface between the gallbladder and the liver, and a transient increase in attenuation of the liver adjacent to the gallbladder20,144,238,248,276,350 (Figs. 42-114 and 42-115). Of all these indings, pericholecystic inlammatory change is believed to be the most speciic20,93,276 because other indings such as gallbladder wall thickening and distention do not necessarily indicate the presence of inlammation. Only about 75% of stones are detected with CT.276 Mirvis and coworkers divided the CT indings of acute cholecystitis into major criteria—including gallstones, thickened gallbladder wall, pericholecystic luid, and subserosal edema—and minor criteria— gallbladder distention and sludge.248 They concluded that the diagnosis of acute cholecystitis can be made if one major and two minor criteria are present. Bennett and colleagues21 reported that the overall sensitivity, speciicity, and accuracy of CT for the diagnosis of acute cholecystitis is 91.7%, 99.1%, and 94.3%, respectively. Although MRI is usually performed only in cases of ambiguous clinical features, it is effective in depicting abnormalities of the gallbladder, especially MR cholangiography using heavily T2-weighted

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A

B

C

D FIG 42-107 Various appearances of radiopaque gallstones on nonenhanced CT. A, Small calciied gallstone with a homogeneous dense appearance. B, Gallstone with a low-density cholesterol center and a dense peripheral rim of calcium. C, Laminated appearance of a gallstone with alternating layers of calcium. D, Gallstone with punctate foci of calcium scattered throughout.

FIG 42-108 Radiolucent gallstone. Nonenhanced CT obtained after

FIG 42-109 Radiolucent gallstones with gaseous central clefts (arrows)

ERCP shows a radiolucent gallstone (arrow). It is seen as a negative illing defect because of the positive contrast agent; otherwise it would be isodense with bile.

that contribute to their loating on nonenhanced CT.

A

B

FIG 42-110 A, Gallstones with low-density centers and subtle

C

A

peripheral calciication (arrows) are seen on nonenhanced CT. B and C, The gallstones have low signal intensity on both T1(B) and T2-weighted (C) MRIs.

B

FIG 42-111 A, Gallstone with a low-density center and dense

C

peripheral rim of calcium is seen on nonenhanced CT. B and C, The gallstone has low signal intensity on T2-weighted MRI (B) but high signal intensity on the T1-weighted image (C).

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B FIG 42-112 A, T2-weighted MRI shows a gallstone with low signal intensity and a central cleft with high signal intensity. B, T1-weighted image shows the gallstone with a low-signal-intensity center and a highsignal-intensity periphery.

A

B FIG 42-113 A, Coronal T2-weighted MRI shows a suspicious gallstone, seen as a round signal void (arrow). B, On the axial T2-weighted image, the signal voids turns out to come from an air bubble (arrow) in the gallbladder.

A

B FIG 42-114 Acute calculous cholecystitis. Nonenhanced (A) and contrast-enhanced (B) CT shows gallbladder wall thickening, high-attenuation bile, a small gallstone obstructing the cystic duct (arrows), and pericholecystic fat stranding suggestive of acute cholecystitis.

CHAPTER 42 sequences. MR indings of acute cholecystitis are similar to those reported with CT, but MRI is superior because it can demonstrate radiolucent gallstones. US is operator dependent in many circumstances, and MR cholangiography is superior to US in depicting gallstones located in the cystic duct and gallbladder neck275 (Fig. 42-116). With the use of a hepatobiliary contrast agent such as mangafodipir trisodium, enhanced T1-weighted MR cholangiography provides functional information about cystic duct patency that is identical to that provided by hepatobiliary scintigraphy.178

Emphysematous Cholecystitis. Emphysematous cholecystitis is an uncommon variant of acute cholecystitis. Vascular compromise of the cystic artery is believed to play a role in the development of this condition, with proliferation of gas-forming organisms in an anaerobic environment and penetration of gas into the gallbladder wall.148,240 Commonly isolated gas-forming organisms are Clostridium perfringens

Biliary Tract and Gallbladder

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and E. coli.240 Emphysematous cholecystitis has distinct differences from ordinary acute cholecystitis, suggesting a separate pathogenesis245; these include a male preponderance (up to 71%), frequent occurrence in diabetic patients (up to 50%), lack of gallstones in up to one third of patients, and higher risk of gallbladder gangrene and perforation. On pathologic review, gallbladders with emphysematous cholecystitis have a higher incidence of endarteritis obliterans, supporting vascular insuficiency as a causative factor. The mortality rate for emphysematous cholecystitis is 15%, versus 4% in uncomplicated acute cholecystitis,114,245 and prompt surgical intervention is required. CT is more sensitive and speciic than US or plain radiographs for the diagnosis of emphysematous cholecystitis.109,114 Therefore CT should be performed if emphysematous cholecystitis is suspected on US, if there is a high clinical index of suspicion, or if the gallbladder cannot be visualized adequately by US in patients with suspected acute cholecystitis. In addition to the indings of acute cholecystitis, CT may show gas within the gallbladder lumen or wall114 and extension into the pericholecystic tissues in patients with emphysematous cholecystitis (Fig. 42-117). If free air is identiied, this indicates perforation of the gallbladder, and urgent surgery is required.

Complications of Acute Cholecystitis. As the pathologic process

FIG 42-115 Acute calculous cholecystitis. Contrast-enhanced CT shows gallbladder wall thickening, a small stone in the gallbladder neck (arrow), blurred interface between the gallbladder and liver, and increased attenuation of the liver adjacent to the gallbladder (arrowheads) suggestive of acute cholecystitis.

A

evolves, acute cholecystitis can be complicated by hemorrhage, gangrene, and perforation. Hemorrhagic cholecystitis. Hemorrhagic cholecystitis is an uncommon complication of acute cholecystitis.153,301 In the presence of gallstones, it is presumed that hemorrhage results from inlammation causing mucosal ulceration and necrosis. Clinically patients with hemorrhagic cholecystitis may present with biliary colic, jaundice, hematemesis, and melena. Rarely patients may present with massive upper gastrointestinal bleeding, hemoperitoneum, or obstruction of the CBD.280 In patients with acalculous cholecystitis, possible causes of gallbladder hemorrhage are tumor, vascular abnormalities (e.g., aneurysm), trauma, anticoagulation, or ectopic pancreatic or gastric mucosa. In addition to the indings of acute cholecystitis, CT in patients with hemorrhagic cholecystitis may show intraluminal hematoma or increased density of bile with a luid-luid level (Fig. 42-118). However, this must be differentiated from other conditions that can cause

B FIG 42-116 Acute calculous cholecystitis. A, T1-weighted MRI shows gallbladder distention, high-signalintensity bile, and multiple small illings defects (arrows) suggestive of gallstones. Note, however, that the bile in the cystic duct has low signal intensity (arrowheads). B, T2-weighted image better demonstrates small gallstones in the cystic duct (arrow). Also shown are the different signal intensities of bile in the gallbladder and cystic duct.

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B FIG 42-117 Emphysematous cholecystitis. Nonenhanced (A) and contrast-enhanced (B) CT shows gas within the gallbladder wall, along with the indings of simple cholecystitis: distended gallbladder, obstructing stone in the cystic duct (arrow in A), pericholecystic fat stranding, and pericholecystic luid collection.

A

B

C FIG 42-118 Hemorrhagic cholecystitis. A, Contrast-enhanced CT shows mild thickening of the gallbladder wall and intraluminal hematoma (arrows) contrasted against the low-attenuation bile. B, ERCP demonstrates an amorphous illing defect (arrows) in the common bile duct, suggestive of hemobilia. C, Nonenhanced CT obtained after ERCP shows intraluminal hematoma, seen as a negative illing defect (arrows) owing to the high attenuation of contrast agent.

CHAPTER 42

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B FIG 42-119 Hemorrhagic cholecystitis. A, T1-weighted MRI shows intraluminal hematoma, seen as a highsignal-intensity lesion contrasted against the low signal intensity of bile. Also noted is a focal defect of the lateral gallbladder wall (arrowheads) suggestive of gangrenous change and a perforated gallbladder. B, T2-weighted image also shows intraluminal hematoma as a low-signal-intensity lesion and a focal defect of the lateral gallbladder wall (arrowheads).

high-density bile, such as recently administered intravenous contrast or milk of calcium. Hemoperitoneum or dilated IHD may be noted if hemorrhagic cholecystitis is associated with gallbladder perforation or obstruction of the CBD due to hemobilia. On MRI, subacute hemorrhage is typically bright on T1-weighted images because of the T1-shortening effects of methemoglobin. On T2-weighted images, a dark rim due to hemosiderin deposition may be appreciated along the inner surface of the gallbladder85 (Fig. 42-119). Gangrenous cholecystitis. Acute cholecystitis may result in gangrene of the gallbladder, with an incidence ranging from 2% to 29.6% in surgical series.2,135,255,348 It is more common in men, patients of advanced age, and those with coexisting cardiovascular disease. Chemical inlammatory reaction of the mucosa with bile salts and progressive distention of the gallbladder lumen leading to vascular compromise are possible mechanisms.232,320 Once gangrenous cholecystitis is suspected, patients generally undergo emergency cholecystectomy to avoid further life-threatening complications, with a higher conversion rate to open cholecystectomy than in uncomplicated acute cholecystitis.149,246,307 CT indings of gangrenous cholecystitis include intraluminal membranes, hemorrhage into the lumen, irregular or absent wall, pericholecystic abscess, and gas in the gallbladder lumen or wall.21,93,196,276 CT with the administration of intravenous contrast is recommended to allow evaluation of gallbladder wall enhancement and mural contour. Bennett and colleagues reported that CT had high speciicity (96%) but low sensitivity (29.3%) for identifying acute gangrenous cholecystitis, with an overall accuracy of 86.7%.21 In their series the CT indings with the highest speciicity for gangrenous cholecystitis were gas in the wall or lumen (100%), intraluminal membranes (99.5%), irregularity or absence of the gallbladder wall (97.6%), and pericholecystic abscess (96.6%) (Fig. 42-120). Among other indings of acute cholecystitis, the presence of pericholecystic luid, greater degree of gallbladder distention in the short axis, and mural thickening were correlated with a higher likelihood of gangrenous cholecystitis. Gallbladder perforation. Gangrene of the gallbladder may eventually result in gallbladder perforation, with an incidence ranging from 8.3% to 11.9%.81,320 Other causes of gallbladder perforation include chronic cholecystitis, cholelithiasis, trauma, neoplasm, steroids, and vascular compromise. The fundus is the most frequent site of

*

FIG 42-120 Gangrenous cholecystitis. Contrast-enhanced CT shows an intraluminal membrane, gas in the gallbladder lumen and wall (arrows), a focal defect in the gallbladder wall (arrowheads), and a pericholecystic abscess (asterisk) suggestive of gangrenous cholecystitis with perforation.

perforation because of the relatively poor blood supply in this area. Niemeier divided gallbladder perforation into three types: (1) acute free perforation into the peritoneal cavity, (2) subacute perforation with pericholecystic abscess, and (3) chronic perforation with cholecystoenteric istula.265 In most series, subacute perforation with pericholecystic abscess is the most common type as a complication of acute cholecystitis.95 A wide range of mortality rates—6% to 70%—has been reported in patients with gallbladder perforation.69,81,95,130,265 In one series there was a 40% mortality rate associated with type 1 free perforation and a 4% mortality rate for type 2.95 Prompt surgical intervention is warranted to decrease morbidity and mortality in patients with gallbladder perforation. Because clinical signs and symptoms are frequently nonspeciic and indistinguishable from those of uncomplicated acute cholecystitis, radiologic studies play a vital role, and it is generally agreed that CT is superior to US for

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this purpose.172,253,277 Interruption of the gallbladder wall or a focal defect on CT may indicate gallbladder perforation. A gallstone may be noted outside of the gallbladder lumen.253 Pericholecystic abscess formation may be conined to the gallbladder fossa or rarely extend into the liver42,277 (Fig. 42-121). There may also be free perforation associated with free luid corresponding to bile (Fig. 42-122). CT is useful for further evaluation or to better determine the extent of inlammation.172,277

Acalculous Cholecystitis

clinical indings are nonspeciic. In many circumstances, US is equivocal because these patients have distended thick-walled gallbladders even in the absence of inlammation, and the sonographic Murphy’s sign is not reliable in these patients. The CT indings are similar to those of acute calculous cholecystitis, with the exception of the absence of gallstones (Figs. 42-123). CT may be more speciic when US indings are nondiagnostic.26,248,249,276 Earlier surgical intervention is considered in patients with acalculous cholecystitis, because they tend to have an increased complication rate and a higher overall mortality.338

Acalculous cholecystitis, an infrequent but clinically serious entity, is found in approximately 5% of all patients undergoing cholecystectomy.8 It usually occurs in the setting of prolonged illness, such as patients with signiicant trauma or long stays in the intensive care unit.20 An increase in bile viscosity from stasis, with subsequent cystic duct obstruction and mucosal ischemia, may be contributing factors. It is often dificult to diagnose acalculous cholecystitis, because the

FIG 42-122 Gallbladder perforation. Coronal contrast-enhanced CT FIG 42-121 Gallbladder perforation. Contrast-enhanced CT shows a focal defect in the gallbladder wall (arrowheads) and pericholecystic abscess (arrows).

A

shows a focal wall defect in the gallbladder fundus (arrowheads), a large amount of peritoneal luid, and diffuse enhancement of thickened peritoneum, suggesting bile peritonitis from gallbladder perforation.

B FIG 42-123 Acute acalculous cholecystitis. Nonenhanced (A) and contrast-enhanced (B) CT shows a distended gallbladder with mild wall thickening, high-attenuation bile, pericholecystic fat stranding, luid collection in the pericholecystic and perihepatic spaces, and absence of gallstones, suggestive of acute acalculous cholecystitis.

CHAPTER 42

Chronic Cholecystitis Chronic cholecystitis is almost always associated with gallstones, but the pathogenesis of this common disease is poorly understood. Although it has been proposed that chronic cholecystitis may develop from recurrent attacks of mild acute cholecystitis, most patients lack a clinical history to support this hypothesis. Although repetitive mucosal trauma by gallstones may explain in part the inlammatory and reparative changes of chronic cholecystitis, there is a poor correlation between the severity of the inlammatory response and the number and size of gallstones. A genetically determined lorid inlammatory response of the gallbladder or an abnormal composition of the bile leading to chemical mucosal injury and stone formation is a possible but currently unproved hypothesis.154 Chronic cholecystitis may have CT and MRI indings similar to those of acute cholecystitis, such as gallstones, wall thickening, and wall enhancement (Fig. 42-124). The gallbladder is sometimes contracted rather than distended (Fig. 42-125). However, gallbladder wall thickening and enhancement in chronic cholecystitis frequently masquerade as gallbladder carcinoma, especially in the absence of gallstones (Fig. 42-126). Conversely there may be minimal abnormality on CT except for the presence of gallstones, which is neither necessary nor suficient for the diagnosis of chronic cholecystitis. In such cases, correlation with the clinical indings is critical, and diagnosis often requires nuclear medicine techniques, particularly to evaluate the gallbladder ejection fraction.

Xanthogranulomatous Cholecystitis. Xanthogranulomatous cholecystitis is an uncommon form of chronic cholecystitis; it is nearly always associated with gallstones and is frequently associated with variable degrees of ibrosis. Although the pathogenesis of this condition is uncertain, it has been suggested that mucosal ulcers or ruptured Rokitansky-Aschoff sinuses, together with outlow obstruction by gallstones and infection, result in the penetration of bile into the gallbladder wall, forming xanthogranulomas.154 On CT, gallstones and masslike irregular thickening of the gallbladder wall are the most common abnormalities (Fig. 42-127). Several studies have reported that intramural hypoattenuated nodules on CT represent a xanthogranulomatous lesion, an abscess, or a combination

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of the two59,171,305 (Figs. 42-128 and 42-129). Chun and associates reported that continuous enhancement of the mucosal line (64%) on postcontrast CT indicated that the main lesion was located in the intramural portion and that the mucosal surface overlying the lesion was either intact or focally denuded.59 Similarly, Shuto and colleagues reported that luminal surface enhancement (70%) corresponded with the presence of an epithelial layer (see Fig. 42-129).305 MRI indings of xanthogranulomatous cholecystitis have rarely been reported, but it is not surprising that MRI may be helpful in depicting the pathologic processes of this entity because of its superb tissue contrast resolution (see Figs. 42-127 and 42-129). Furuta and coworkers described the signal intensity of the gallbladder wall as low on T1-weighted images and moderately high on T2-weighted images.106 They also noted multiple intramural hyperintense nodules on T2weighted images that were nonenhanced on postcontrast T1-weighted images. In their cases, histologic examination of specimens showed several abscesses with numerous foam cells in the gallbladder wall. Similarly, Shuto’s group found intramural nodules with very high signal intensity on T2-weighted images in four of ive patients; these nodules were not enhanced on postcontrast studies and consisted of necrosis or abscess histopathologically.305 In their series the slightly high-intensity areas in the gallbladder wall on T2-weighted images were strongly enhanced on postcontrast T1-weighted images during the late phase and consisted of abundant proliferation of foamy cells. It is important for the radiologist to distinguish xanthogranulomatous cholecystitis from gallbladder cancer. The characteristic CT and MRI indings of xanthogranulomatous cholecystitis—including a patent mucosal line or luminal surface enhancement on CT, and intramural nodules with hypoattenuation on CT or very high signal intensity on T2-weighted images—can be helpful in differentiating the two conditions.

Complications of Chronic Cholecystitis Mirizzi’s syndrome. Mirizzi’s syndrome, typically a complication of long-standing calculous cholecystitis, is deined as narrowing of the extrahepatic bile duct, causing obstructive jaundice by impaction of gallstones within the cystic duct and subsequent extrinsic compression or inlammation.247 A long or low insertion of the cystic duct into the

B FIG 42-124 Chronic cholecystitis. A, Contrast-enhanced CT shows a small gallstone (arrow) and mild thickening of the gallbladder wall. B, MR cholangiogram better demonstrates the irregularity of the gallbladder wall at the fundus (arrowheads), as well as gallstones (long arrows). There is also a small stone in the common bile duct (short arrow).

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D FIG 42-125 Chronic cholecystitis. Nonenhanced (A) and contrast-enhanced (B) CT shows a contracted gallbladder with mild wall thickening. Axial T2-weighted MRI (C) and MR cholangiography (D) better demonstrate the small gallstone (arrow) and irregularity of the gallbladder wall at the fundus.

FIG 42-126 Chronic cholecystitis. Contrast-enhanced CT shows irregular thickening of the gallbladder wall, without a deinite stone.

CBD may predispose to this condition.185,278 Preoperative diagnosis of Mirizzi’s syndrome can be challenging because of the inlammation, ibrosis, and distortion of structures at the level of obstruction. In a recent surgical series, this syndrome was found in 1.13% of all cholecystectomies, but the diagnosis could be made preoperatively in only 56% of patients.162 Mirizzi’s syndrome may be suggested on CT or MRI by identiication of a stone within the cystic duct, with concurrent biliary ductal dilatation at the level of the cystic duct176,330 (Fig. 42-130). However, on CT, Mirizzi’s syndrome may mimic carcinoma of the CHD or cystic duct if the gallstones are radiolucent (Fig. 42-131). In such cases it is important to ascertain that there is no deinite mass or lymphadenopathy, as would be expected with bile duct cancer.25 Sometimes by means of pressure necrosis, impacted gallstones in the gallbladder neck or cystic duct may erode into the adjacent CHD or the surrounding tissue of the hepatoduodenal ligament. Gallstone ileus. Gallstone ileus is rare, occurring in 0.3% to 0.5% of all cases of cholelithiasis.75 It is more prevalent in women than in men, with a ratio of 3 : 1 to 16 : 1.287 The majority of obstructing stones

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FIG 42-127 Xanthogranulomatous cholecystitis. Nonenhanced (A) and contrast-enhanced (B) CT shows a large gallstone, masslike irregular thickening of the gallbladder wall, and increased enhancement of the surrounding liver. The thickened gallbladder wall has low signal intensity on the T1-weighted MRI (C) and moderately high signal intensity on the T2-weighted image (D).

A

B FIG 42-128 Xanthogranulomatous cholecystitis. A, Contrast-enhanced CT shows masslike irregular thickening of the gallbladder wall and multiple intramural hypoattenuated nodules (arrows). Also note the indings of cirrhosis: surface nodularity and ibrotic low attenuation in the liver periphery, as well as a large amount of ascites. B, Photograph of the cut surface demonstrates multiple yellowish intramural nodules and hemorrhage (arrows) in the irregularly thickened gallbladder wall.

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D FIG 42-129 Xanthogranulomatous cholecystitis. A, Contrast-enhanced CT shows a gallstone, irregular thickening of the gallbladder wall, and multiple intramural hypoattenuated nodules (arrows). Also noted is the presence of luminal surface enhancement and focal discontinuity (arrowheads). B and C, Intraluminal nodules (arrows) exhibit variable signal intensity on the T1-weighted MRI (B) and bright high signal intensity on the T2-weighted image (C). Focal discontinuity of the luminal surface (arrowheads) is also appreciated on both T1- and T2-weighted images. D, Photograph of cut surface demonstrates multiple xanthogranulomas seen as yellowish intramural nodules (arrows) in the irregularly thickened gallbladder wall.

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B FIG 42-130 Mirizzi’s syndrome. A, Contrast-enhanced CT shows wall thickening in the cystic duct containing the gallstone (arrows) and a compressed common hepatic duct, appearing as a triangular shape (arrowhead). B, ERCP shows nonopaciication of the cystic duct and marked narrowing of the common hepatic duct by smooth extrinsic indentation (arrows) at the level of cystic duct insertion, suggestive of Mirizzi’s syndrome.

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FIG 42-131 Mirizzi’s syndrome. A, Contrast-enhanced CT shows dilated intrahepatic bile duct and an illdeined soft tissue masslike lesion (arrows) around the cystic duct. B, T2-weighted MRI demonstrates a small gallstone (arrow) seen as a dark illing defect contrasted against the high signal intensity of bile in the center of the ill-deined lesion. MR cholangiography (C) and ERCP (D) reveal dilated intrahepatic bile duct and narrowing of the common hepatic duct by smooth extrinsic indentation (arrows) at the level of cystic duct insertion, suggestive of Mirizzi’s syndrome.

in gallstone ileus originate in the gallbladder, but this does not account for all cases; this condition has also been reported in patients who had undergone prior cholecystectomy.75,199 When it occurs as a complication of chronic cholecystitis, the gallstone erodes through the gallbladder wall and into the adjacent bowel through a cholecystoenteric istula, most commonly between the gallbladder and duodenum.9,75 Patients may have had a recent acute biliary episode preceding the onset of gallstone ileus. Once the stone enters the alimentary tract, the site of obstruction is usually the terminal ileum because it is the narrowest portion of the small bowel; however, less than half of these stones cause obstruction, and many are evacuated uneventfully in the stool.75,138,199 In general, gallstones causing ileus are single, large, and faceted.344 Although plain radiographs may demonstrate the traditional triad of small bowel obstruction, pneumobilia, and ectopic gallstone, not all gallstones are radiopaque on plain radiographs, and pneumobilia may not be appreciated. CT is more accurate in diagnosing gallstone ileus by demonstrating a stone within the bowel lumen (usually the distal ileum), dilated small bowel loops proximal to the stone, and air in the bile duct and gallbladder.78,115,198,286 CT may also demonstrate a

distorted gallbladder in direct continuity with a thickened duodenal wall226,286 (Fig. 42-132). Porcelain gallbladder. Dystrophic calciication can be associated with ibrous tissue in the gallbladder wall in chronic cholecystitis, resulting in the so-called porcelain gallbladder. The term porcelain emphasizes the blue discoloration and brittle consistency of the gallbladder.23,161 Calcium may be found either as a broad continuous plaque in the muscle layer or as punctate foci in the mucosal layer (Fig. 42-133). CT is the best method for depicting dystrophic calciication in the gallbladder wall, although plain radiographs and US may also demonstrate this inding. Sometimes the calciied rim of a large stone illing the gallbladder lumen or a deposit of lipiodol in the gallbladder wall after transcatheter arterial chemoembolization for hepatic malignancy may mimic porcelain gallbladder. For unknown reasons, porcelain gallbladder is frequently associated with carcinoma of the gallbladder23 (Fig. 42-134). Therefore special attention to any sign of carcinoma is mandatory when reading CT scans in these patients. Even when the patient has few or no gallbladder symptoms and there is no evidence of gallbladder carcinoma, prophylactic cholecystectomy is recommended.

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E FIG 42-132 Gallstone ileus. A, Contrast-enhanced CT shows a large stone (arrow) in the gallbladder neck and masslike thickening of the gallbladder wall adherent to the adjacent duodenum (asterisk). B, The patient presented with sudden abdominal pain 3 months later. Plain abdominal radiograph shows small bowel ileus, but neither pneumobilia nor ectopic gallstone is evident. C, Contrast-enhanced CT shows a large istula (arrowhead) between the gallbladder and duodenum, with disappearance of the gallstone. D, Nonenhanced CT reveals that the gallstone (arrow) has migrated to the ileum, causing small bowel ileus. E, Follow-up CT 6 days later shows migration of the gallstone (arrow) to the rectum and partial improvement of small bowel ileus.

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Hyperplastic Cholecystosis The generic term hyperplastic cholecystosis was irst introduced by Jutras155 to describe a group of noninlammatory conditions of the gallbladder, including cholesterolosis and adenomyomatosis, in which benign proliferation of normal tissue is the important feature. However, except that neither is an inlammatory or a neoplastic condition, cholesterolosis and adenomyomatosis have little similarity in terms of cause and clinical features.24

Cholesterolosis. Cholesterolosis consists of multiple deposits of cholesterol-laden macrophages in the lamina propria of the gallbladder wall, forming cholesterol polyps.24,155 These are generally too small to be seen on CT and MRI but are better appreciated on US (Fig. 42-135).

Adenomyomatosis. Adenomyomatosis is characterized by hyperFIG 42-133 Porcelain gallbladder. Nonenhanced CT shows porcelain gallbladder with punctate foci of calciication.

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plastic muscular wall thickening, mucosal overgrowth, and intramural diverticula, crypts, or sinus tracts—so-called Rokitansky-Aschoff sinuses.24,63,100,155,347 There are three different morphologic types of

B FIG 42-134 Porcelain gallbladder. A, Nonenhanced CT shows irregular calciication in the gallbladder wall, suggestive of porcelain gallbladder. B, Contrast-enhanced CT shows an irregular mass (arrows) enguling the calciication, suggestive of gallbladder carcinoma. Also noted are multiple lymphadenopathies (arrowheads) in the hepatoduodenal ligament and around the left gastric artery, suggestive of metastases, and a dilated intrahepatic bile duct.

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B FIG 42-135 Cholesterolosis. A, Nonenhanced CT shows mild thickening of the gallbladder wall. B, Photograph of the pathologic specimen shows multiple yellowish lecks of cholesterol deposits.

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adenomyomatosis: diffuse (generalized), segmental (annular), and localized. Diffuse adenomyomatosis causes thickening of the muscle layer (often three to ive times thicker than normal), irregularity of the mucosal surface, and glandlike or cystlike structures in the wall, which prompted the terms cholecystitis glandularis proliferans and cystic cholecystitis.182 In the segmental form, annular thickening of the gallbladder wall may cause focal stricture, dividing the lumen into separate interconnected compartments.19 The localized variety is most commonly seen in the fundus and is often called adenomyoma.155 The CT and MRI abnormalities of adenomyomatosis attributable to the characteristic macroscopic pathologic features have been the concern of many radiologic investigators.43,107 Besides the nonspeciic inding of diffuse or focal gallbladder wall thickening, identiication of intramural diverticula (Rokitansky-Aschoff sinuses) is a prerequisite for the diagnosis of adenomyomatosis. Although CT may be limited in detecting adenomyomatosis with minimal abnormalities and in differentiating adenomyomatosis from gallbladder carcinoma,43,107 the diagnosis of adenomyomatosis can be made with reasonable accuracy when a thickened gallbladder wall in the diseased segment appears to contain small cystlike spaces,43,136 corresponding to intramural diverticula pathologically136 (Figs. 42-136 to 42-138). T2-weighted MRIs and MR cholangiography can better demonstrate these intramural cystlike spaces, which appear as bright high-signal-intensity areas in

A

the thickened gallbladder wall—the “pearl necklace” sign (see Fig. 42-136).124,175,355 Yoshimitsu et al.355 also reported that on dynamic MRI, diffuse-type adenomyomatosis typically shows early mucosal and subsequent serosal enhancement over the Rokitansky-Aschoff sinus, and localized adenomyomatosis exhibits homogeneous enhancement, showing smooth continuity of the surrounding gallbladder epithelium.

Gallbladder Neoplasms Benign Gallbladder Neoplasms. Except for adenomas, benign neoplasms are rare in the gallbladder, although a variety of epithelial and stromal tumors have been reported. Adenomas are often small and asymptomatic and are usually discovered incidentally during cholecystectomy, with an incidence of 0.3% to 0.5%.154 When it is large enough, an adenoma may appear as a small polypoid lesion along the gallbladder wall on CT or MRI (Fig. 42-139).

Gallbladder Carcinoma. Most neoplasms that arise from the gallbladder are carcinoma. Adenocarcinoma is the most common histologic type, accounting for 85% to 90% of cases. Squamous or adenosquamous cell carcinoma, neuroendocrine carcinoma (e.g., small cell carcinoma), and undifferentiated carcinoma including sarcomatoid carcinoma have also been reported.169 The peak

B

C FIG 42-136 Adenomyomatosis. A, Contrast-enhanced CT shows localized thickening of the gallbladder wall at the fundus, with multiple intramural cystlike structures (arrows). Axial T2-weighted MRI (B) and MR cholangiogram (C) better demonstrate intramural cystlike spaces appearing as bright high-signal-intensity areas in the thickened gallbladder wall—the so-called pearl necklace sign (arrows).

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B FIG 42-137 Localized adenomyomatosis. A, Contrast-enhanced CT shows localized thickening of the gallbladder wall at the fundus and a few cystlike intramural lesions (arrows). B, Photograph of the gross specimen demonstrates intramural cysts (arrows) at the gallbladder fundus.

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C FIG 42-138 Diffuse adenomyomatosis. A, Contrast-enhanced CT shows a markedly thickened gallbladder wall and profuse mucosal enhancement radiating to the serosal side. B, MR cholangiogram demonstrates multiple intramural cysts (arrows) appearing as bright high-signal-intensity areas in the thickened gallbladder wall, suggestive of diffuse adenomyomatosis. C, Photograph of the gross specimen shows a markedly thickened gallbladder wall consisting of scattered glandular tissue with ibrosis and smooth muscle microscopically, consistent with diffuse adenomyomatosis.

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B FIG 42-139 Gallbladder adenoma (polypoid type). A, Contrast-enhanced CT shows an intraluminal polypoid lesion (arrow) with intense contrast enhancement. B, Coronal T2-weighted MRI better demonstrates the papillary surface of the lesion (arrow).

occurrence of gallbladder carcinoma is in the sixth and seventh decades of life, and there is a female predilection of 2 : 1 to 3 : 1.154 The four most important factors associated with the development of gallbladder carcinoma are genetic factors, gallstones, congenital abnormal pancreaticobiliary ductal union, and porcelain gallbladder.118,154,205,288,303,313 Patients with gallbladder carcinoma may have a mutation of the TP53 gene, overexpression of the c-erbB-2 gene, and decreased expression of the nm23 gene.58,102,103 The risk of gallbladder carcinoma is increased in patients with gallstones; 75% of patients with gallbladder carcinoma have gallstones.118,303,313 The female predominance of gallbladder carcinoma parallels the high incidence of gallstones in women.154 An association between gallbladder carcinoma and anomalous pancreaticobiliary ductal union has been suggested; as a result of the relux of pancreatic juice into the CBD, the mixture of pancreatic juice and bile may lead to chronic inlammation of the gallbladder, with subsequent metaplasia, dysplasia, and carcinoma.181,252 As mentioned earlier, porcelain gallbladder is frequently associated with carcinoma of the gallbladder, for unknown reasons (see Fig. 42-134).23 The clinical features of gallbladder carcinoma are often nonspeciic and overlap those seen in cholelithiasis and cholecystitis. Symptoms and signs of malignancy may not appear until the carcinoma has spread to other sites. Sometimes patients with carcinoma involving the neck of the gallbladder present with secondary acute cholecystitis due to outlow obstruction. Occasionally gallbladder carcinoma is an incidental inding on imaging studies. The typical CT indings of gallbladder carcinoma include three patterns: a mass replacing the gallbladder fossa, an intraluminal polypoid mass, and gallbladder wall thickening. A mass replacing the gallbladder fossa is the most common type in many series; the mass ills most of the enlarged and deformed gallbladder, obscuring the lumen.143,192,318,341 These masses typically have low attenuation with variable enhancement, most commonly irregular peripheral enhancement in the early phase and progressive enhancement in the late phase. This type of gallbladder carcinoma often invades adjacent structures, including the liver (Figs. 42-140 and 42-141). An intraluminal polypoid mass is less common; differentiation of polypoid gallbladder carcinoma from benign polyps is based on size, with polypoid gallbladder

carcinoma typically larger than 1 cm112 (Figs. 42-142 and 42-143). Most benign polyps (e.g., cholesterol polyps) and adenomas are small, measuring less than 1 cm. The gallbladder wall-thickening type of carcinoma may be dificult to distinguish from adenomyomatosis and cholecystitis (especially chronic cholecystitis and xanthogranulomatous cholecystitis) (Fig. 42-144). It has been reported that FDG PET may help distinguish between benign and malignant gallbladder lesions (see Figs. 42-143 and 42144).266,267 Using dual–time point FDG PET, Nishiyama and coworkers proposed that a delayed scan is more helpful than an early scan for evaluating malignant lesions because of increased lesion uptake and increased lesion-to-background contrast266; they also indicated that the diagnostic performance depends on C-reactive protein levels. Falsepositive diagnoses of gallbladder carcinoma are still possible with FDG PET because benign lesions such as adenomyomatosis and tuberculosis may appear as hot lesions.233,283 On MRI, gallbladder carcinomas usually have increased signal intensity and poorly delineated contours on T2-weighted images and either isointense or hypointense signal on T1-weighted images compared with the liver.292 MR cholangiography is especially useful for gallbladder carcinoma associated with anomalous pancreaticobiliary ductal union (see Fig. 42-141). Otherwise the enhancement pattern of gallbladder carcinoma on dynamic MRI is similar to that reported with CT. Gallbladder carcinoma commonly spreads by direct extension into adjacent structures such as the liver, hepatoduodenal ligament, colon, and duodenum (Figs. 42-145 and 42-146). The liver is the most common site of invasion because of its proximity and the lack of serosa in the gallbladder wall where it is adjacent to the liver. The incidence of liver invasion at the time of presentation varies from 34% to 89%.311 Lymphatic spread to regional and distant lymph nodes is also common in gallbladder carcinoma. Engels et al.86 reported that the foramen of Winslow lymph node and the superior pancreaticoduodenal node are the most frequent sites of nodal metastases (see Fig. 42-145). The other pathways of tumor spread in gallbladder carcinomas are hematogenous metastasis to the liver, intraductal tumor spread, and peritoneal seeding (see Fig. 42-145).303 Biliary obstruction is present in about 50% of cases of gallbladder carcinoma, which is attributed to direct invasion

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C FIG 42-140 Gallbladder carcinoma (mass-replacing type). A and B, Contrast-enhanced CT shows a mass replacing the gallbladder lumen, with irregular stippled enhancement in the early phase (A) and diffuse enhancement in the late phase (B). Invasion of the adjacent liver is also suggested (arrowheads). C, Photograph of the gross specimen shows a large irregular mass that had replaced the gallbladder and invaded the liver (arrowheads).

of the bile duct in the porta hepatis, to metastatic lymphadenopathy, or to intraductal spread of tumor (see Figs. 42-145 and 42-146).192,324 CT plays a key role in the staging of gallbladder carcinoma. Overall accuracy for assessing resectability has been reported as 85% to 93% with dual-phase helical CT or MDCT.160,193 However, the ability to identify early-stage disease on CT remains disappointing. Yoshimitsu and associates correlated the performance of helical CT with pathologic indings according to the tumor-node-metastasis (TNM) system and concluded that helical CT provides acceptable sensitivity and speciicity for T2 and more advanced lesions but poor sensitivity for T1 lesions (33%).356

Other Malignant Gallbladder Neoplasms. Nonepithelial malignant tumors such as Kaposi’s sarcoma, leiomyosarcoma, malignant ibrous histiocytoma, angiosarcoma, rhabdomyosarcoma, and lymphoma may occur in the gallbladder. The radiologic appearance of the gallbladder sarcoma has rarely been reported. Although gallbladder

sarcoma can present as a bulky mass with central necrosis,169 it may be dificult to distinguish from gallbladder carcinoma (Fig. 42-147). Primary lymphoma involving the gallbladder is extremely rare. Secondary lymphoma of the gallbladder is less rare but still uncommon and has been described as a feature of disseminated lymphoma.250 Lymphoma may appear as an intraluminal polypoid lesion or as wall thickening on CT169 (Fig. 42-148). Metastases to the gallbladder are rare but can originate from virtually any source. Malignant melanoma is the most common cause of metastatic tumors of the gallbladder, accounting for more than 50% of all cases of metastases found in the gallbladder.116 Although the majority of metastatic lesions are located on the serosal surface owing to peritoneal implantation, some metastases present as intraluminal polypoid masses169 (Fig. 42-149). It has been reported that 18 FDG PET can enhance the detection of gallbladder metastases from melanoma.285 Text continued on p. 1260

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F FIG 42-141 Gallbladder carcinoma (thickened-wall type). A and B, Contrast-enhanced CT shows a mass partly obscuring the gallbladder lumen, with irregular peripheral enhancement in the early phase (A) and progressive enhancement in the late phase (B). C, On a T2-weighted MRI the mass has increased signal intensity and a poorly delineated contour. Dynamic contrast-enhanced early-phase (D) and late-phase (E) MRI show an enhancement pattern similar to that on CT. F, MR cholangiography demonstrates a long common channel of the common bile duct and main pancreatic duct (arrow), suggesting an associated anomalous pancreaticobiliary ductal union.

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B FIG 42-142 Gallbladder carcinoma (polypoid type). A, Contrast-enhanced CT shows a large intraluminal polypoid mass with diffuse contrast enhancement. B, T2-weighted MRI better demonstrates the papillary surface of the mass.

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B FIG 42-143 Gallbladder carcinoma (polypoid type). A, Contrast-enhanced CT shows a small intraluminal polypoid lesion with subtle contrast enhancement. B, Increased lesion uptake is noted on FDG PET, suggesting malignancy.

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B FIG 42-144 Gallbladder carcinoma (thickened-wall type). A, Contrast-enhanced CT shows focal thickening of the gallbladder wall at the fundus. B, Increased lesion uptake is noted on FDG PET, suggesting malignancy.

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FIG 42-145 Gallbladder carcinoma with metastasis to the liver and lymph nodes. A and B, Contrastenhanced CT shows a mass replacing the gallbladder fossa with irregular peripheral enhancement, suggestive of gallbladder carcinoma. Direct liver invasion (arrowheads), hilar invasion (asterisk), multiple lymph node metastases (large arrows), and liver metastases (small arrows) are also suggested. Bile duct dilatation is presumed to be caused by hilar invasion.

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C FIG 42-146 Gallbladder carcinoma (squamous cell type). A, Contrast-enhanced CT shows a mass replacing the gallbladder fossa, with irregular peripheral enhancement suggestive of gallbladder carcinoma. Pathologic diagnosis of percutaneous needle biopsy was squamous cell carcinoma of the gallbladder, and the patient underwent chemotherapy. B, Follow-up CT 3 months later shows increased size and cavitary change of the mass, which contains a large amount of air and luid (asterisk). Liver metastasis (arrowhead) and bile duct dilatation are also noted. C, CT at a lower level reveals a large istula (arrows) in the mass replacing the gallbladder and duodenum. Asterisk shows air and luid.

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E FIG 42-147 Malignant ibrous histiocytoma of the gallbladder. A, Contrast-enhanced CT shows a mass replacing the gallbladder and mild dilatation of the intrahepatic bile duct. B, T2-weighted MRI shows the mass with moderately high signal intensity and a poorly delineated contour. C, T1-weighted MRI shows the low signal intensity of the mass. D and E, Dynamic contrast-enhanced MRIs show the mass obscuring the gallbladder with irregular peripheral enhancement in the early phase (D) and progressive enhancement in the late phase (E).

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FIG 42-148 Gallbladder lymphoma. Contrast-enhanced CT shows irregular thickening and enhancement of the gallbladder wall. Pathologic diagnosis of diffuse large B-cell lymphoma was made after cholecystectomy.

FIG 42-149 Metastatic melanoma to the gallbladder. Contrastenhanced CT shows a large intraluminal mass in the gallbladder, with marked hypoattenuation and a poorly delineated contour. Mild enhancement at the base of the lesion (arrows) and a bile cleft between the mass and the adjacent gallbladder wall can be seen.

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325. Todani T, Watanabe Y, Mizuguchi T, et al: Hepaticoduodenostomy at the hepatic hilum after excision of choledochal cyst. Am J Surg 142:584–587, 1981. 326. Todani T, Watanabe Y, Narusue M, et al: Congenital bile duct cysts: Classiication, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst. Am J Surg 134:263–269, 1977. 327. Todani T, Watanabe Y, Toki A, et al: Carcinoma related to choledochal cysts with internal drainage operations. Surg Gynecol Obstet 164:61–64, 1987. 328. Toombs BD, Foucar E, Rowlands BJ, et al: Multiseptate gallbladder. South Med J 75:610–612, 1982. 329. Tsai HM, Lin XZ, Chen CY, et al: MRI of gallstones with different compositions. AJR Am J Roentgenol 182:1513–1519, 2004. 330. Turner MA, Fulcher AS: The cystic duct: Normal anatomy and disease processes. Radiographics 21:3–22, 288-294, 2001. 331. Udelsman R, Sugarbaker PH: Congenital duplication of the gallbladder associated with an anomalous right hepatic artery. Am J Surg 149:812–815, 1985. 332. Ueda J, Hara K, Ohishi H, et al: High density bile in the gallbladder observed by computed tomography. J Comput Assist Tomogr 7:801–804, 1983. 333. Ueda J, Kobayashi Y, Nishida T: Computed tomography evaluation of high-density bile in the gallbladder. Gastrointest Radiol 15:22–26, 1990. 334. Ukaji M, Ebara M, Tsuchiya Y, et al: Diagnosis of gallstone composition in magnetic resonance imaging: In vitro analysis. Eur J Radiol 41:49–56, 2002. 335. van Sonnenberg E, Ferrucci JT, Jr: Bile duct obstruction in hepatocellular carcinoma (hepatoma): Clinical and cholangiographic characteristics. Report of 6 cases and review of the literature. Radiology 130:7–13, 1979. 336. Vezina WC, Paradis RL, Grace DM, et al: Increased volume and decreased emptying of the gallbladder in large (morbidly obese, tall normal, and muscular normal) people. Gastroenterology 98:1000–1007, 1990. 337. Reference deleted in proofs. 338. Wang AJ, Wang TE, Lin CC, et al: Clinical predictors of severe gallbladder complications in acute acalculous cholecystitis. World J Gastroenterol 9:2821–2823, 2003. 339. Wastie ML, Cunningham IG: Roentgenologic indings in recurrent pyogenic cholangitis. Am J Roentgenol Radium Ther Nucl Med 119:71–77, 1973. 340. Weinbren K, Mutum SS: Pathological aspects of cholangiocarcinoma. J Pathol 139:217–238, 1983. 341. Weiner SN, Koenigsberg M, Morehouse H, et al: Sonography and computed tomography in the diagnosis of carcinoma of the gallbladder. AJR Am J Roentgenol 142:735–739, 1984. 342. Weinstein JB, Heiken JP, Lee JK, et al: High resolution CT of the porta hepatis and hepatoduodenal ligament. Radiographics 6:55–74, 1986. 343. Weissleder R, Stark DD, Compton CC, et al: Cholecystitis: Diagnosis by MR imaging. Magn Reson Imaging 6:345–348, 1988. 344. Whitesell FB, Jr: Gallstone ileus. Am Surg 36:317–322, 1970. 345. Wiesner RH, LaRusso NF: Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology 79:200–206, 1980. 346. Willi UV, Reddish JM, Teele RL: Cystic ibrosis: Its characteristic appearance on abdominal sonography. AJR Am J Roentgenol 134:1005– 1010, 1980. 347. Williams I, Slavin G, Cox A, et al: Diverticular disease (adenomyomatosis) of the gallbladder: A radiological-pathological survey. Br J Radiol 59:29–34, 1986. 348. Wilson AK, Kozol RA, Salwen WA, et al: Gangrenous cholecystitis in an urban VA hospital. J Surg Res 56:402–404, 1994. 349. Yamamoto M, Takasaki K, Yoshikawa T, et al: Does gross appearance indicate prognosis in intrahepatic cholangiocarcinoma? J Surg Oncol 69:162–167, 1998.

CHAPTER 42 350. Yamashita K, Jin MJ, Hirose Y, et al: CT inding of transient focal increased attenuation of the liver adjacent to the gallbladder in acute cholecystitis. AJR Am J Roentgenol 164:343–346, 1995. 351. Yeh TS, Jan YY, Tseng JH, et al: Malignant perihilar biliary obstruction: Magnetic resonance cholangiopancreatographic indings. Am J Gastroenterol 95:432–440, 2000. 352. Yoon KH, Ha HK, Kim MH, et al: Biliary stricture caused by blunt abdominal trauma: Clinical and radiologic features in ive patients. Radiology 207:737–741, 1998. 353. Yoon KH, Ha HK, Kim CG, et al: Malignant papillary neoplasms of the intrahepatic bile ducts: CT and histopathologic features. AJR Am J Roentgenol 175:1135–1139, 2000. 354. Yoshida H, Itai Y, Minami M, et al: Biliary malignancies occurring in choledochal cysts. Radiology 173:389–392, 1989. 355. Yoshimitsu K, Honda H, Jimi M, et al: MR diagnosis of adenomyomatosis of the gallbladder and differentiation from gallbladder carcinoma: Importance of showing Rokitansky-Aschoff sinuses. AJR Am J Roentgenol 172:1535–1540, 1999. 356. Yoshimitsu K, Honda H, Shinozaki K, et al: Helical CT of the local spread of carcinoma of the gallbladder: Evaluation according to the

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43 Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases Achille Mileto and Daniel T. Boll

“Is life worth living?—It all depends on the liver!” —William James, 1842-1910 Over more than 3 millennia the liver held a central and unsurpassed role among all human organs, manifested in coeval theogony, poetry, and fairy tales. The liver was chosen to be the seat of the soul, intelligence, and passion, equipped with particular divine protection and hoped to be indestructible, relecting the prodigious recuperative powers of hepatic parenchyma.33 In Egyptian mythology, Isis’s envoy Imsety (18th Dynasty, 15701350 BC) was the guardian of the liver of the deceased on its journey to the afterlife. Later, Greek mythology emphasized the particular physical and psychological qualities of torture when the liver is being targeted. According to Hesiod (≈700 BC) an eagle devoured Prometheus’s liver after he stole ire from Zeus. Because of the recuperative powers of hepatic parenchyma, his torture had to be endured for 13 generations until Prometheus was saved by Heracles. Unfortunately, Achilles and Tityus later met the same fate. According to Galen (129-199) the liver is of vital physical and psychological relevance to all human beings. The four bodily humors— blood, phlegm, yellow bile, and black bile—were thought to give rise to the sanguine, phlegmatic, choleric, and melancholic temperaments, respectively; health thereafter was deined as equilibrium in these four humors. Physical and psychological distress was a symptom of imbalance in these humors, as phrased by Horace (65-8 BC): “My liver swells with bile dificult to repress.” Renaissance poetry emphasized the ancient belief that the liver is the seat of love, as seen in Shakespeare’s (1564-1616) rhapsody Love’s Labour’s Lost: “This is the liver-vein, which makes lesh a deity.” Fairy tales of more recent centuries picked up the basic principle of the liver being the seat of the soul and intelligence. According to the Brothers Grimm (1785/86-1863/59, respectively), Snow White’s stepmother ordered the woodsman not just to kill her but to cut out her liver to ensure her physical and psychological disappearance. It all depended on the liver!

NORMAL LIVER ANATOMY AND VARIANTS Normal Anatomy The liver, as the largest of all abdominal organs, commands the right upper abdominal quadrant, though it can extend into the epigastrium and as far as the left upper abdominal quadrant, abutting the splenic contour. Taking variations of liver volume and dimensions due to ethnicity into account, in the male the liver weighs from 1.4 to 1.7 kg and in the female 1.2 to 1.5 kg. Its greatest transverse measurement is from 20 to 26 cm; vertically near its lateral surface the liver measures 15 to 21 cm, and its greatest anteroposterior diameter (determined at

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the level of the upper right kidney) measures 7 to 12 cm. The hepatic parenchyma is surrounded by a dense layer of connective tissue forming the liver capsule.

Surface Anatomy. The liver’s external structure features convex diaphragmatic and concave visceral surfaces. The diaphragmatic surface is perfectly itted and afixed by intervening connective tissue to a triangular section of the undersurface of the diaphragm termed the bare area. Other than the bare area, only the fossa of the gallbladder, the fossa of the inferior vena cava (IVC), and the suprarenal impression are not covered by peritoneum. The bare area’s upper and lower margins are demarcated by peritoneal relections forming the anterior and posterior layers of the coronary ligament, respectively. The posterior layer of the coronary ligament continues with the right layer of the lesser omentum as the hepatorenal ligament. The anterior and posterior layers of the hepatic coronary ligament converge on the right and left margins of the bare area, forming the right and left triangular ligaments. The right triangular ligament is a small peritoneal fold that extends toward the diaphragm. The left triangular ligament on the other hand is of considerable size and gives off connective tissue tracts extending to the diaphragm as well as portions of the falciform ligament. The main anterior portion of the left triangular ligament forms the left layer of the falciform ligament, whereas the right layer of the falciform ligament is a continuation of the anterior layer of the coronary ligament. The falciform ligament thereby forms a broad and thin peritoneal fold that dissects the liver into its right and left hepatic lobes and is in contact with the peritoneum posterior to the rectus abdominis musculature and the diaphragm. Intraabdominal ixation of the liver to the undersurface of the diaphragm is therefore realized by intervening connective tissue of the bare area as well as by means of connective tissue tracts extending from the coronary and triangular ligaments; the rather lax falciform ligament attachment to the peritoneum only limits lateral displacement. At the liver’s visceral surface, predominantly fossae and issures deine the lobar anatomy. Two fossae extending sagittally are joined by a transverse issure, forming a letter H–like structure. The left limb of the letter H is known as the left sagittal fossa, a deep groove extending from the anterior surface to the posterior contour of the organ, thereby marking the division of the liver into the right and left hepatic lobes. The anterior part of the left sagittal fossa houses the umbilical vein during fetal circulation and its adult remains, the ligamentum teres, thereafter.135 The ligamentum teres itself extends toward the base of the falciform ligament and runs together with the paraumbilical veins between its right and left layers from the umbilicus to the left portal vein. The posterior part of the left sagittal fossa contains the ductus venosus, which during fetal circulation forms a bypass between the left portal vein and the left hepatic vein, functioning as a left-sided

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portosystemic shunt, and during adulthood holds its remains, the ligamentum venosum.135 The anterior and posterior parts of the left sagittal fossa can be separated by the pons hepatis. The right limb of the letter H consists anteriorly of the fossa for the gallbladder and posteriorly of the fossa for the IVC. The latter usually appears as a short and deep impression; occasionally liver parenchyma can surround the IVC and thereby form a complete canal. Three veins—the left, middle, and right hepatic veins—perforate the loor of the fossa and drain into the IVC. These two fossae are free of peritoneal lining and are separated by the caudate process of the liver. The bar connecting the two limbs of the letter H is termed the transverse issure. Anterior to the transverse issure lies the quadrate lobe; posterior, the caudate lobe of the liver. The transverse issure represents the porta hepatis, a 5-cm-deep groove containing the hepatoduodenal ligament, which transmits anteriorly the hepatic duct on the right and the hepatic artery on the left; posteriorly and partially in between the two resides the portal vein as well as hepatic nerves and lymphatics. The hepatic artery carries oxygenated blood to the liver, constituting about 20% to 25% of the total blood volume to the organ. The portal vein on the other hand carries nutrient-rich blood from the digestive system, comprising 75% to 80% of total hepatic blood volume. The hepatic artery and portal vein ramify in parallel to one another. In healthy persons, the caliber of the portal venous branches is larger than those of corresponding arterial branches. Venous return is realized through the three main hepatic veins that drain directly into the IVC. The visceral undersurface of the liver is uneven owing to its proximity to the antral esophagus, stomach, right colonic lexure, upper pole of the right kidney, right adrenal gland, and descending portion of the duodenum. Each of the organs forms characteristic impressions. Additionally a rounded eminence, the tuber omentale, abuts the gastric concavity of the lesser curvature in front of the lesser omentum. The diaphragmatic surface can be riddled with furrows from prominent muscular bundles forming the diaphragmatic crura, seen particularly in patients with chronic lung diseases.

Functional Segmental Anatomy. Advances in hepatic surgery have made the lobar segmentation of the liver into right, left, quadrate, and caudate lobes obsolete. This division has yielded to a more functionally oriented classiication primarily based on the surgical deinition of feasible intrahepatic boundaries of resection, which in turn is based on segmental hepatic coniguration.17,18,21,47,61 Centrally located in each of the hepatic segments is a segmental branch of the portal vein and hepatic artery as well as a segmental bile duct. The solitary distal hepatic veins lie between the individual segments. Several systems have been suggested for classifying the segments of the liver, many of them quite similar; the most common is the nomenclature proposed by Bismuth-Couinaud, which will now be considered in detail. In the Bismuth-Couinaud system, segment I corresponds to the caudate lobe. This segment is in the unique position of receiving branches from both the main portal vein and its right and left branches, termed the portal trinity. Furthermore, it does not drain into the hepatic veins but directly into the IVC. All remaining liver segments (II to VIII) are deined by their positions relative to branches of the portal and hepatic veins. The portal venous plane is deined as the transverse plane dissecting the liver at the level of the portal venous bifurcation into superior and inferior hepatic segments. The portal vein divides early into left and right portal venous branches, with the left portal pedicle supplying segments II through IV, thereby forming the segmental left hepatic lobe, and the right portal pedicle (segments V through VIII) thus constituting the segmental right hepatic lobe.

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The left portal vein, after giving off a caudate branch, divides into its terminal branches, the left lateral and left medial portal venous branches. The left lateral portal venous branch supplies superior segment II, located lateral to the left hepatic vein and above the portal venous plane. The left medial portal venous branch supplies inferior segment III located laterally to the left hepatic vein and beneath the portal venous plane as well as segment IV. Segment IV is delineated medially by the middle hepatic vein and laterally by the left hepatic vein and can be further subdivided into a superior segment IVa and an inferior segment IVb in regard to the portal venous plane. The right portal vein divides into its right anterior and right posterior terminal branches. The right anterior portal venous branch supplies the anterior-inferior segment V located between the middle and right hepatic veins and below the portal venous plane, whereas the anterior-superior segment VIII can be found contiguous to segment V but directly above the portal venous plane. The right posterior portal venous branch perfuses the posterior-inferior segment VI located posterolaterally to the right hepatic vein but beneath the portal venous plane, while the posterior-superior segment VII can be found adjacent to segment VI directly above the portal venous plane (Fig. 43-1).

Liver Anatomy Variants A signiicant number of normal variants in liver morphology and hepatic vascularity occur. Knowledge of the most common anatomic variants of the liver is essential, in particular to diagnose generalized hepatomegaly versus lobar hypertrophy, as well as to identify the spatial hepatic location of focal lesions based on the functional segmentation nomenclature proposed by Bismuth-Couinaud.

Variants in Morphology. Common normal variants in liver morphology include the horizontal elongation of the lateral segment (Bismuth-Couinaud segment II) of the left hepatic lobe, which can extend into the left upper abdominal quadrant and eventually abut or even wrap around the splenic contour. This anatomic variant is more common in women. However, because of the different computed tomography (CT), magnetic resonance imaging (MRI), and perfusion characteristics of hepatic and splenic parenchyma, this variant usually does not impose problems during radiologic interpretation. Another normal variant of liver size and shape is vertical elongation of the right lobe, termed a Riedel lobe (Fig. 43-2). The presence of a Riedel lobe usually results from a prominent inferiorly positioned narrow right lobe of the liver that signiicantly extends the expected conines of the liver. A Riedel lobe is more frequently found in women.180 It has to be differentiated from extracapsular extension caused by a liver tumor, in particular hepatic adenoma or metastasis. A prominent caudate lobe can show a pronounced extension, which is then termed a hepatic papillary process (Fig. 43-3). This normal variant can simulate a mass in the portocaval region.9,72 Differentiation between an extrahepatic portocaval mass and a papillary process can be facilitated by recognizing the continuity of this process with the caudate lobe on contiguous axial sections, as well as multiplanar reformations (MPR), preferably in the coronal plane. Following a partial hepatectomy, rapid hypertrophy of the remaining liver segments can occur. This hypertrophy results in distortion of the expected anatomy as the major vessels become displaced by the enlarging segments. Furthermore, segmental hepatic resections have to be differentiated from congenital hypoplasia of the left lobe. Assessment of the clinical history of the patient and direct patient communication remain of paramount importance when interpreting complex anatomy.

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FIG 43-1 Triple-phase contrast-enhanced MDCT imaging during the hepatic arterial phase (A, D, G, and J), the portal venous phase (B, E, H, and K) and the delayed hepatic phase (C, F, I, and L) at different levels in regard to the portal venous plane: upper superior plane (A to C), lower superior plane (D to F), portal venous plane (G to I), and inferior plane (J to L). A to C, In the upper superior hepatic plane the hepatocentric venous branches of the right hepatic vein (RHV), middle hepatic vein (MHV), and left hepatic vein (LHV) are clearly seen, differentiating the superior hepatic segments (2, 4a, 8, and 7) that are supplied by the lateral branch (lb-LPV) and medial branch (mb-LPV) of the left portal vein as well as the anterior branch (ab-RPV) and posterior branch (pb-RPV) of the right portal vein, respectively. D to F, The lower superior hepatic plane shows the more intrahepatic segments of right hepatic vein (RHV), middle hepatic vein (MHV), and left hepatic vein (LHV) as well as lateral branch (lb-LPV) and medial branch (mb-LPV) of the left portal vein and anterior branch (abRPV) and posterior branch (pb-RPV) of the right portal vein. The issure for the ligamentum venosum (FLV) separates the upper caudate. G to I, In the portal venous plane the hepatocentric right portal vein (RPV) and left portal vein (LPV) can be seen with their corresponding lateral branch (lb-LPV) and medial branch (mb-LPV), as well as anterior branch (ab-RPV) and posterior branch (pb-RPV), respectively. Hepatocentric left hepatic and right hepatic arteries can be seen. Segment 1, the caudate lobe, is also visible. The terminal left hepatic vein (t-LHP) can bee seen to the left of the issure of the ligamentum teres (FLT); the terminal terminal middle (t-MHP) and right (t-RHP) are on its right side. J to L, In the inferior hepatic plane the inferior hepatic segments (3, 4b, 6, and 5) and their analogously supplying distal portal venous branches can be found.

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Variants in Vascularity. Common normal variants in hepatic vas-

FIG 43-2 Precontrast T1-weighted hepatic MRI in a 77-year-old woman with Riedel’s lobe (arrows) resulting from a prominent inferiorly positioned narrow right lobe of the liver that signiicantly extends the expected conines of the liver.

cularity have to be identiied prior to implementation of the BismuthCouinaud system to describe the location of hepatic focal lesions. Prior knowledge of replaced hepatic arteries is of importance in clinical scenarios of planned partial hepatectomies and extensive pancreatic surgery. Interindividual frequency and degree of variability of the hepatic arterial and venous as well as portal venous vasculature, particularly in the right liver lobe, is signiicant. Variants in arterial hepatic supply exist as accessory or replaced right hepatic arteries, commonly originating from the superior mesenteric artery, then located posterior in regard to the portal vein. In up to 20% of all patients, a duplication of the right hepatic vein may be found. High-resolution imaging of the hepatic veins and the portal venous system has shown that only the anterosuperior and posteroinferior sectors are visualized without signiicant variation in vascularity.36,70,112,215 It was shown that portal venous branches often cross the plane of the right hepatic vein, and no portal venous plane can be identiied separating the anterosuperior and posteroinferior sectors; hence the right hepatic vein cannot serve as a reliable landmark for dividing the anteromedial and posterolateral segments of the right hepatic lobe. The left liver lobe presents fewer variations in vascular anatomy. Analogously, variants in arterial hepatic supply exist as accessory or replaced left hepatic arteries, commonly originating from the left gastric artery and then always coursing within the issure of the venous ligament. Duplication of the middle hepatic vein is seen in about 5% of patients, of the left in about 15%. There may also be some variation in arterial structure, particularly in segment IV. In about 8% of all patients the dorsal portion of segment IV is supplied by the right hepatic artery, hence from the functionally contralateral side.105,131,141,206 In about 30% of patients, accessory portal segments analogous to the caudate lobe (Bismuth-Couinaud segment I) may be observed, each of which is supplied directly from the main portal venous trunk or from its right branch.10,35,150,215 Recognizing the signiicant interindividual variation in hepatic vascularity, advanced and less radical hepatic surgery aims to reduce the reliance on a rigid schematic division of the liver into segments and considers instead the patient’s individual vascular situation in surgeries involving segments or even subsegments of the liver.67,92,96,188 A liver segment is deined solely by its vascular supply. Based on highresolution multidetector (MD)CT and MR data sets, it is possible to construct three-dimensional (3D) hepatic maps of vascular anatomy to assist surgeons in exact and effective preoperative planning of the procedure.

HEPATIC IMAGING TECHNIQUES Multidetector CT Imaging of the Liver

FIG 43-3 T1-weighted contrast-enhanced MRI of a 55-year-old man with hypertrophy and extension of the caudate lobe (arrows), also known as a papillary hepatic process. Note the simple cyst along the issure for the ligamentum teres (arrowhead).

MDCT remains the predominant imaging modality to visualize the liver. Besides the general availability of this modality, the role of MDCT is primarily deined by its excellent morphologic visualization capabilities, in particular of diffuse or focal intrahepatic lesions as well as of anatomic relationships between the liver and adjacent organs. These imaging capabilities have been further enhanced since overall detector row numbers have increased from 4-slice to 16-slice, and of late to 64-slice detector arrays that allow partial and multisegmental raw-data reconstructions and fundamentally affect imaging protocols. MDCT imaging in particular beneited from acquisition of high-resolution volume image data sets with drastically reduced scan times due to signiicantly shorter gantry rotation periods (as short as 300 milliseconds), which can be further decreased (to about 80 milliseconds) by employing a dual x-ray tube approach.54,92,188

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Normal CT attenuation of the liver in unenhanced imaging studies varies interindividually between 55 and 65 Hounsield units (HU). Usually the normal liver appears homogeneous at CT visualization, and its attenuation exceeds that of the spleen in healthy individuals by about 10 HU. The relatively large interindividual range in attenuation values is due to the varying fat and glycogen content of the organ. Increased diffuse deposition of fat leads to a reduction in attenuation, whereas increased glycogen is relected as an increase in CT measured density.48,225 Blood circulation in the liver comprises two major components, the hepatic artery and the portal vein. Because of this dual-source hepatic blood supply, the pattern of extracellular parenchymal contrast uptake and the associated changes in tissue attenuation over time follow a complex multicompartmental perfusion model. The overall hepatic perfusion cycle can be differentiated into three idealized hepatic perfusion phases: (1) arterial phase, (2) redistribution/portal venous phase, and (3) equilibrium/hepatic venous phase. Because of the temporal proximity and relatively short duration of each of these perfusion phases, and owing to multiple extrahepatic factors that inluence systemic and portal venous perfusion, an optimized and individualized regimen of intravenous contrast agent and saline chaser application has to be applied: • Application of contrast agent and saline chaser by means of mechanical power injectors is mandatory to realize homogenous low rates of 1 to 5 mL/sec. • Venous access is usually supplied by a 16- to 20-gauge indwelling venous catheter placed in a right cubital or antecubital vein. • By choosing a nonionic and more highly concentrated contrast agent solution containing at least 370 mg iodine/mL, an overall contrast volume of 80 mL is suficient to perfuse the liver with 30 g of iodine, resulting in a 25% increase in iodine application during the arterial phase. This reduces the overall injected iodine dose signiicantly compared to less-concentrated contrast agent solutions at ixed transit times from the cubital/ antecubital vein to the liver.11,123,197 • By taking into account the individual variations of cardiac output, blood volume, and visceral perfusion, the need for bolus tracking techniques as supplied by all MDCT imaging systems to determine the arrival time of the contrast agent bolus is a mandatory prerequisite. Bolus tracking relies on sequential lowdose scans obtained at the level of the upper abdominal aorta; aortic enhancement values are immediately displayed. When aortic enhancement reaches a predeined threshold of approximately 150 HU, hepatic scanning is initiated. The delay time between adequate bolus detection in the upper abdominal aorta, CT table motion, and subsequent initiation of scanning is as low as 5 seconds on current MDCT imagers. Approximately 10 seconds after contrast threshold–based scanning initiation during the early arterial phase, contrast enhancement of the abdominal aorta and hepatic artery is observed without admixture of enhanced portal venous blood. The late arterial phase at approximately 20 seconds after scanning initiation leads to a clear depiction of the hepatic artery and its branches, owing to distinctive contrast enhancement. However, a minimal admixture of enhanced portal venous blood may already have occurred. The redistribution/portal venous inlow phase, imaged about 30 seconds after scan initiation, allows early visualization of the portal vein and its intrahepatic branches, in contrast to the still unenhanced hepatic veins. Maximum contrast enhancement of the portal vein and its intrahepatic branches is reached after approximately 40 seconds. If monoslice CT scanners are used to perform biphasic liver scanning, all

the contrast-enhanced phases previously described would be combined in one hepatic arterial/portal venous phase.55,65 The hepatic venous phase can be acquired 60 seconds after scan initiation. Simultaneous enhancement of hepatic and portal veins will thus be visualized. Because of retained contrast agent, focal liver lesions such as cholangiocarcinoma beneit from further delayed hepatic imaging, after the parenchymal contrast has mostly been drained from the liver.

MDCT Imaging Strategies. The multitude of clinical scenarios that require or include hepatic MDCT imaging cannot be appropriately addressed with one comprehensive imaging protocol. Instead a manageable list of MDCT imaging protocols to answer speciic clinical situations have been deined throughout medical institutions. Furthermore, each of these imaging protocols is tailored to the individual patient, taking individual descriptors and parameters such as body habitus, body weight, heart rate, and limitations in the patient’s range of motion and positioning into account. Valid indications for non–contrast-enhanced (NCE) hepatic MDCT examinations include (but are not limited to) the search for calciications in settings such as hemangioendothelioma, calciied metastases of mucinous adenocarcinoma, and postinlammatory calciications in cases of alveolar echinococcosis. Furthermore, unenhanced MDCT can help detect intrahepatic CT-opaque bile duct concretions. Subcapsular or parenchymal hemorrhage can also be visualized. Finally, postprocedural visualization of the lipiodol distribution pattern following intraarterial embolization of liver tumors is another valid indication for NCE hepatic MDCT imaging. Whenever contrast-enhanced MDCT imaging of the liver is part of a more comprehensive imaging protocol—for example, including the entire chest, abdomen, and pelvis in the imaging ield of view (FOV) without suspected speciic hepatic pathology—usually only one hepatic contrast phase is acquired. In this contrast monophase imaging scenario, the portal venous imaging phase will be preferred. Dedicated multiphase hepatic imaging can be performed subsequently to further evaluate suspected hepatic indings. In clinical scenarios with a known or suspected hypervascular primary neoplasm outside the liver for which there are suspected hypervascular hepatic metastases, a dedicated hepatic dual-phase imaging protocol should be performed. This protocol includes MDCT imaging during both the hepatic late arterial and the portal venous phase but does not include an NCE phase. Conirmed or suspected diagnoses of breast carcinoma, renal cell carcinoma, melanoma, and neuroendocrine tumors (e.g., islet cell tumors, carcinoid and thyroid carcinomas) would call for the dual-phase hepatic imaging protocol. Known or suspected cirrhosis or hepatocellular carcinoma as well as suspected benign primary liver lesions (e.g., focal nodular hyperplasia or hepatic adenoma) would be imaged by means of MDCT employing a triple-phase imaging protocol. This protocol includes a noncontrast imaging phase in addition to hepatic arterial and portal venous imaging phases; it also calls for a larger volume of contrast agent and higher infusion rates compared to the dual-phase protocol. Oftentimes a delayed phase acquired 10 to 15 minutes after initiation of contrast is performed as well. In patients with known or suspected cholangiocarcinoma another triple-phase imaging protocol (unenhanced, portal venous, and delayed) addresses a pathophysiologic phenomenon of delayed contrast agent washout and subsequent relative hyperattenuation of cholangiocarcinomas in comparison to surrounding hepatic parenchyma. For preoperative planning in anticipation of a partial hepatic resection, high-resolution imaging of the celiac axis, proximal superior

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Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases

mesenteric artery, and porta hepatis is mandatory. A hepatic resection protocol combines high-resolution imaging of the arterial vasculature with a limited imaging FOV followed by a standard portal venous imaging phase.

MDCT Imaging Protocols. The family of available CT imagers covers a huge bandwidth of detector conigurations from single- to 128-detector arrays, which allow helical scanning at various temporal and spatial resolutions. Fundamental differences in detector conigurations of equally sized and equally spaced detector arrays from asymmetric detector conigurations of detector sizes and arrangements result in MDCT imaging protocols with unique parameters for almost each available MDCT imaging system. The advent of dual-source and/ or dual-detector MDCT imagers that allow for simultaneous dualenergy examinations will increase possible combinations of imaging parameters even further. This overview of MDCT imaging protocols attempts to cover a representative selection of widely used equally sized and equally spaced 16-detector and 128-detector MDCT images. Adaptations according to individual scanner conigurations, however, can be performed using these imaging protocols as groundwork (Tables 43-1 to 43-6) (see Fig. 43-1). Dual-energy CT applications for liver imaging. Dual-energy MDCT allows for spectral analyses and thus tissue characterization based on using two x-ray beams of distinct and known energy distributions tuned to the characteristic absorption proiles of different tissues and injected contrast materials. This has the potential for enhancing inherent tissue differences and enabling selective contrast material detection.125 The identiication, isolation, and quantiication of iodinecontaining voxels throughout the liver enable the creation of iodine

TABLE 43-1

Protocol

Collimation

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp Not applicable

Slice thickness Pitch Table speed/gantry rotation Tube current Tube voltage Delay from initiation of bolus

TABLE 43-4

maps from contrast-enhanced dual-energy MDCT studies (DECT). Alternatively, virtual nonenhanced image series might be obtained by subtracting the iodine contribution from the contrast-enhanced image data sets. The latter approach has the potential for substantially reducing the radiation dose to patients for multiphase MDCT protocols of the liver125 (Fig. 43-4). A more recent promising application for DECT imaging of the liver is based on material density analysis. Material density images are

Hepatic Monophase Contrast MDCT Protocol: Portal Venous Phase TABLE 43-2 Parameter

Protocol

Collimation

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp 30 sec

Slice thickness Pitch Table speed/gantry rotation Tube current Tube voltage Delay from initiation of bolus

Hepatic Dual-Phase Contrast

TABLE 43-3

MDCT Protocol PROTOCOL Parameter

Arterial Phase

Collimation

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec

Hepatic NCE MDCT Protocol

Parameter

1273

Slice thickness Pitch Table speed/gantry rotation Tube current

Tube voltage Delay from initiation of bolus

Automatic adaptation 100-700 mA/ 340-380 mA 120 kVp Arterial bolus tracking

Portal Venous Phase 64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/ 340-380 mA 120 kVp 30 sec

Hepatic Triple-Phase Contrast MDCT Protocol PROTOCOL

Parameter

Non–Contrast-Enhanced

Arterial Phase

Portal Venous Phase

Collimation

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp Not applicable

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp Arterial bolus tracking

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp 30 sec

Slice thickness Pitch Table speed/gantry rotation Tube current Tube voltage Delay from initiation of bolus

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TABLE 43-5

PROTOCOL Parameter Collimation

Slice thickness Pitch Table speed/gantry rotation Tube current Tube voltage Delay from initiation of bolus

Non–ContrastEnhanced

Arterial Phase

Portal Venous Phase

Delayed Phase

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp N/A

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp Arterial bolus tracking

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp 30 sec

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.7 55.0 mm/up to 0.28 sec Automatic adaptation 100-700 mA/340-380 mA 120 kVp 15 min

The Partial Liver Resection

TABLE 43-6

MDCT Protocol PROTOCOL Parameter

Arterial Phase

Portal Venous Phase

Collimation

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 1.25 mm 1.375/1.75 55.0 mm/up to 0.28 sec

64 × 1.5 mm or 64 × 0.6 mm (=128 z-lying spot)/32 × 1.5 mm 3-5 mm 1.375/1.75 55.0 mm/up to 0.28 sec

Automatic adaptation 100-700 mA/ 340-380 mA 120 kVp Arterial bolus tracking

Automatic adaptation 100-700 mA/ 340-380 mA 120 kVp 30 sec

Slice thickness Pitch Table speed/gantry rotation Tube current

Tube voltage Delay from initiation of bolus

obtained using a two-material decomposition algorithm, which works by irst establishing a basis pair and identifying associated attenuation characteristics of each material in the basis pair.13 Then each voxel is decomposed proportionally into the two-material basis pairs according to the attenuation characteristics of that speciic voxel as measured at each energy level (typically 80 and 140 kVp). Material density images represent the relative distribution of densities in a given material, which produce the observed projections at the high and low energies.13 Therefore the values obtained on material density images do not represent absolute density measurements, but rather they relect the true proportion or relative quantity of material under investigation.13 As an example, for a material basis pair composed of fat and iodine, the effective fat density image is represented by the fat-iodine data set, whereas the effective iodine density image is represented by the iodinefat data set. A region-of-interest measurement obtained on a fat-iodine image data set represents the relative effective density of fat without the iodine contribution. Similarly, an ROI measurement drawn over an iodine-fat image depicts the relative effective density of iodine without fat within a given target area.13

Magnetic Resonance Imaging MRI of the liver has been proven to be a competitive and comprehensive modality to assess morphology and functional characteristics of the liver in clinical scenarios of diffuse and focal liver diseases. Current clinical abdominal MRI is performed at magnetic ield strengths from 0.5 to 3.0 tesla (T). Concurrent technical improvements such as the development of more powerful gradient systems and phased-array body coils, as well as implementation of advanced imaging sequence designs such as respiratory-triggered 3D data acquisition and sparse k-space sampling schemes, permit high-quality examination of the liver with both T1- and T2-weighted pulse sequences. Timing parameters of T1- and T2-weighted pulse sequences for dedicated hepatic imaging (e.g., repetition time [TR], echo time [TE]) are in part based on liver tissue–speciic relaxation times, T1 and T2, which in turn show a strong dependency on the surrounding magnetic ield strength. At 0.5 T magnetic ield strength, liver parenchyma has a T1 relaxation time of approximately 327 to 518 milliseconds and a tissue-speciic T2 relaxation time of 55 to 62 milliseconds. At 1.5 T, hepatic tissue’s relaxation time has signiicantly increased for T1 to 547 to 568 milliseconds and minimally decreased for T2 to 51 to 56 milliseconds. At 3.0 T, liver-speciic T1 relaxation time has increased further to 809 milliseconds, while liver-speciic T2 relaxation time is further reduced to approximately 45 to 50 milliseconds.43,63,216 The underlying principle of tissue-speciic T1-weighted imaging is to use the shortest possible TE to maximize hepatic contrast and the number of slices attainable performing a breath-hold examination. Hepatic T2-weighted imaging on the other hand requires a TR in excess of at least four times the tissue’s speciic T1 relaxation time and a TE that approximates the tissue’s speciic T2 relaxation time. Therefore sequence designs of T1- and T2-weighted pulse sequences have to be partially redesigned for each given ield strength to allow high-quality hepatic imaging in reasonable time frames. A comprehensive evaluation of the liver by means of MRI frequently involves intravenous contrast agents. As opposed to intravenous contrast in hepatic CT imaging, which is based on nonionic extracellular iodine-containing solutions with various concentrations of iodine, contrast-enhanced MRI of the liver uses a cluster of contrast agents that include nonspeciic agents with an extracellular distribution, materials that are taken up speciically by hepatocytes and are partially excreted through the biliary system, as well as solutions that are targeted speciically to the Kupffer cells as part of the reticuloendothelial system (RES).

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Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases

A

B

C

D

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FIG 43-4 Dual-energy MDCT of the liver in a 52-year-old man. Dual-energy MDCT worklow with conventional grayscale data set (A), water-density (B), iodine-density (C) and color-coded iodine overlay map (D).

Nonspeciic gadolinium chelates without tissue-speciic biodistribution conined to extracellular spaces have been commercially available since 1986. Paramagnetic gadolinium shortens tissue-speciic relaxation times, leading to an increase in hepatic tissue signal intensities on T1-weighted sequences. Rapid redistribution of gadolinium chelates from intravascular to extracellular spaces requires a small-volume bolus injection of this contrast agent at up to 2 mL/sec, with an individual-adapted contrast dose of 0.1 to 0.2 mmol/kg of body weight. These gadolinium chelates are available in various compositions as gadopentetate dimeglumine (Gd-DTPA), gadoteridol (Gd-HP-DO3A), gadodiamide (Gd-DTPA-BMA), gadoversetamide (Gd-DTPA-BMEA), gadoterate meglumine (Gd-DOTA), and gadobutrol (Gd-BT-DO3A), with varying approval from governmental healthcare authorities, in particular the latter not having been approved by the U.S. Food and Drug Administration (FDA). Gadofosveset trisodium represents a new class of blood-pool contrast agents speciically designed for visualization of abdominal or limb vessels in patients with known or suspected vascular diseases. Whereas in the past, extremely attractive safety proiles have been reported using these contrast agents, of late reports have been made of a possible association between gadolinium chelates and development of nephrogenic systemic ibrosis in patients with impaired renal function. Until further scientiic evalua-

tions of this phenomenon have been conducted, patients with a glomerular iltration rate of less than 30 mL/min/1.73 m2 should not receive gadolinium-containing contrast agents.23,120,124,169,198 Hepatocyte-targeted contrast agents undergo active transport into the intracellular space of the hepatocytes, where they are further metabolized. They are partly eliminated through the biliary system and subsequently allow parenchymal and biliary assessment employing T1-weighted pulse sequences. Hepatocyte-selective contrast agents are either manganese based, as mangafodipir trisodium (Mn-DPDP), or gadolinium based, as gadoxetic acid disodium (Gd-EOB-DTPA) or gadobenate dimeglumine (Gd-BOPTA), the latter two combining the properties of nonspeciic extracellular with tissue-speciic intracellular contrast agents. The pharmacodynamics of these contrast agents differ signiicantly. Mangafodipir trisodium is administered as a slow intravenous infusion over 2 minutes; the overall dose of 5 to 10 mmol/kg of body weight is less than 10% of that for gadolinium-based agents. Therefore dynamic imaging is not possible, and imaging of mangafodipir trisodium in its short-term extracellular distribution does not add valuable information. In patients with pronounced cirrhosis and subsequent hepatic impairment, an association with an elevated risk to experience neurologic complications has been described. Gadoxetic acid disodium and gadobenate dimeglumine on the other hand allow

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for imaging during the arterial phase, redistribution/portal venous phase, and equilibrium/hepatic venous phase, comparable to the other gadolinium chelates; however, they add an excretory phase to the contrast-enhanced liver imaging protocol. Because Gd-EOB-DTPA and Gd-BOPTA feature a T1 relaxivity slightly higher than conventional gadolinium-based agents, an overall contrast dose of 0.025 to 0.1 mmol/kg of body weight is suficient to acquire the same information.40,52,170,223,224 RES-speciic contrast agents are selectively incorporated by the Kupffer cells, which comprise 2% of the liver volume. These RESspeciic contrast agents consist of small iron particles, which when larger than 50 nm are termed superparamagnetic iron particles (SPIO) and when smaller than 50 nm are called ultrasmall superparamagnetic iron particles (USPIO). Ferumoxides diluted in 5% dextrose solution are administered intravenously at least 30 minutes prior to imaging at a dosage of 10 µmol/kg of body weight, but imaging can also occur as long as 4 hours after administration. Approximately 80% of injected ferumoxides are taken up by macrophages in the Kupffer cells, and the remaining 20% are stored in the spleen and bone marrow. The superparamagnetic effect is based on susceptibility artifacts generated by the incorporated ferumoxides and subsequent shortening of tissue-speciic T2 relaxation times. T2-weighted pulse sequences are conventionally used for parenchymal postcontrast imaging of RES-speciic contrast agents. As with all tissue-speciic contrast agents, lack of this particular tissue will lead to lack of uptake of contrast material; in the case of the negative SPIO and USPIO contrast agents, the surrounding liver will appear hypointense. Positive contrast agents, such as mangafodipir trisodium and gadobenate dimeglumine, will lead to a hyperintense visualization of hepatic parenchyma. Imaging characteristics of hepatic lesions will be based on the presence or absence of liver-speciic Kupffer cells or hepatocytes.57,101,102,147,201 On NCE pulse sequences, physiologic liver parenchyma shows a higher T1 signal intensity and a lower T2 signal intensity compared to the spleen. The hyperintensity of hepatic parenchyma on T1-weighted pulse sequences is due to the large amount of hepatic protein and rough endoplasmic reticulum within the hepatocytes. Sharply demarcated from the hepatic parenchyma is the more hypointense biliary tree as well as portal and hepatic veins; hyperintense inlow artifacts, however, can be observed on individual images. Therefore NCE T1-weighted pulse sequences should not be evaluated for the patency of hepatic or portal venous vasculature. Bile throughout the biliary tree appears hyperintense on T2weighted pulse sequences in contrast to the hypointense visualization of the surrounding liver parenchyma. Heavily T2-weighted pulse sequences are subsequently used for acquisition of MR cholangiopancreatography (MRCP) images, in which only the biliary tree is visualized against a hypointense background. Indications for MRI of the liver include: • Characterization of diffuse or focal hepatic lesions of uncertain etiology • Determination of the extent and segment localization of hepatic malignancies prior to planned partial liver resection • Follow-up in cases of known primary or secondary hepatic malignancies

MRI Strategies. MR sequences for hepatic imaging continue to evolve at a fast rate, whereas the clinical applications of each of these sequences have changed little over time. Unchanged remain the three basic considerations if MRI has been chosen for hepatic imaging: to improve parenchymal contrast, to suppress respiratory motion artifact, and to ensure complete anatomic coverage. Guaranteeing these three basic considerations in order to assess various clinical scenarios of

differing hepatic diseases using the most advanced designs of T1-weighted and T2-weighted imaging sequences remains the greatest challenge in hepatic MRI. A major recent development—particularly in abdominal MRI— was implementation of parallel imaging techniques using spatial information from single coils of a phased-array set to perform a portion of the spatial encoding normally accomplished by time-consuming gradients and radiofrequency (RF) pulses, thereby signiicantly reducing acquisition times. Different approaches such as the simultaneous acquisition of spatial harmonics (SMASH) technique or the sensitivity encoding (SENSE) procedure have been proposed, realizing spatial encoding with multiple spatial-distinct receiver coils for a sparse sampling of k-space. Subsequently, linear combinations of component coil signals are used to emulate the effects of phase encoding gradients. However, basic parallel imaging techniques require detailed and time-consuming coil mapping procedures for calibration purposes to prevent image distortions. Faster and more sophisticated calibration techniques acquire a block of extra lines in the center of k-space and subsequently perform a sliding block reconstruction. Unlike the internal autocalibration functions of SMASH techniques (AutoSMASH), data from multiple lines from all coils are used to it an autocalibration signal line in one single coil. This it gives the weights that can be used to generate the missing lines from that coil. Once all of the lines are reconstructed for a particular coil, a Fourier transformation can be used to generate the uncombined image for that coil. This process is repeated for each coil of the array, and inally the full set of images can be combined using a sum-of-squares reconstruction. This approach is also known as the generalized autocalibrating partially parallel acquisition (GRAPPA) technique.66,189,190 Acceleration of individual imaging sequences and use of respiratory triggering techniques (e.g., respiratory bellows or implemented diaphragmatic navigators) ensure that T1-weighted and T2-weighted pulse sequences can be acquired in excellent quality. Whereas T1-weighted imaging is currently performed during a single breath hold—particularly important for dynamic contrast-enhanced (DCE) imaging—T2-weighted pulse sequences are obtained in a seamless multisegmental end-expiratory fashion using respiratory triggering. Developments and improvements in magnetic ield strengths, gradient technology, and receiver coil design, as well as implementation of parallel imaging techniques and respiratory triggering procedures, allow acquisition of a comprehensive hepatic MR exam in less than 30 minutes. For hepatic MRI the following sequence types are used: single-shot fast-spin echo (SSFSE), balanced steady-state free precession (SSFP), dual gradient echo in-phase (IP) and opposed-phase (OP) imaging, dynamic multiphase 3D spoiled gradient echo, diffusionweighted imaging (DWI), and MRI elastography. Single-shot fast-spin echo. SSFSE acquisition schemes (e.g., half-Fourier acquisition single-shot turbo-spin echo [HASTE]) are based on a spin echo sequence with data acquisition after an initial preparation pulse for contrast enhancement, further employing a long echo train, with each echo being individually phase-encoded. Additionally a sparse k-space sampling scheme is used, acquiring only 56% of the raw-data matrix; partial Fourier reconstruction results in T2-weighted hepatic MRIs. An interleaved acquisition scheme is usually chosen, with long TRs to allow the spin system to recover between excitation pulses. The parenchymal contrast on SSFSE acquisition schemes may be improved with spectral fat-suppression techniques or with an inversion recovery pulse (short tau inversion recovery [STIR]) that provides additional contrast.78,80,95,200 FSE sequences can be combined with respiratory triggering procedures to allow 3D data sampling on heavily T2-weighted hepatic MRIs,

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Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases

resulting in high-resolution MRCP image data sets. These MRCP data sets can be further postprocessed with maximum intensity projections (MIPs). Balanced steady-state free precession. SSFP acquisition schemes (FIESTA, trueFISP) are based on a gradient echo sequence with a steady state developing for transverse and longitudinal magnetization, as well as a chosen TR that is shorter than hepatic T1 and T2 relaxivity parameters. Balanced gradients in all spatial directions are used between any RF excitation pulses to return the spin system to the same phase it had before RF pulses were applied. In this way, contrast as well as spatial and temporal resolutions allow this sequence type to become a practical whole-body application. Acquired images show T2* over T1 imaging characteristics. A major advantage of this sequence type is its insensitivity to motion artifacts. This sequence type is mainly used as a bright blood technique for unenhanced imaging of the portal vein. Dual gradient echo in-phase and opposed-phase imaging. This incoherent gradient echo sequence (e.g., multiplanar gradient recalled [MPGR], fast low-angle shot [FLASH]) is characterized by low lip angles and uses a semirandom spoiler gradient after each echo readout to spoil the steady-state situation to destroy any remaining transverse magnetization by causing a spatially dependent phase shift. This spoiler gradient allows extremely short TRs, resulting in heavily T1-weighted image series. TEs have to be kept as short as possible to avoid susceptibility artifacts. This sequence type is also suitable for bolus timing; a single transverse slice positioned at the level of the upper abdominal aorta will detect the injected contrast bolus and, by improving the widely used “guesstimation” approach, initiate DCE MRI thereafter. However, by adjusting the TE appropriately, scans can be obtained with water and lipids in either an IP or OP state. On IP images, the signal from both water and fat protons contributes to tissue signal intensity. On OP images, signal from fat protons cancels that of water protons. This technique is useful in evaluating focal or diffuse fatty iniltration and for tissue characterization, such as in the case of incidentalomas in the adrenal glands. Usually the boundaries between tissues with different water or fat content appear black on OP images, also known as India ink artifact or chemical shift artifact of the second kind. Choice of TE for IP and OP images depends on ield strength. High-ield-strength MR imagers with implemented strong gradient systems allow acquisition of different IP and OP pairs; however, to determine the underlying phenomenon of signal intensity variation, either due to IP and OP spin vectors or free induction decay, radiologists must be aware of the TE pair selected.136,138,139,161,165,181 Dynamic multiphase 3D spoiled gradient echo. The advent of high-performance gradient systems and implementation of parallel imaging techniques (e.g., liver acquisition with volume acceleration [LAVA], volumetric interpolated breath-hold examination [VIBE], driven equilibrium [DRIVE]) have rendered 3D acquisition schemes with zero-ill interpolation, overlapping thin sections, and effective spectral fat saturation a superior method compared to previously established two-dimensional (2D) and multisectional DCE T1-weighted imaging. Detection and characterization of diffuse and focal liver diseases is signiicantly enhanced when the entire liver can be imaged during a single suspended respiration. Speciically, to optimize arterialphase timing, a single-breath-hold triple-arterial-phase acquisition— three successive acquisitions in the same breath hold—is increasingly adopted (Fig. 43-5). This technique has a number of advantages over a single arterial-phase acquisition technique. Indeed, a triple-arterialphase acquisition allows for increasing the likelihood of acquiring at least one precisely timed late hepatic arterial-phase image set while also

1277

mitigating the effect of transient artifacts by isolating them to one or two of the image sets. In addition a 2D parallel acceleration technique (controlled aliasing in parallel imaging results in higher acceleration [CAIPIRINHA]) combined with a 3D T1-weighted spoiled gradient recalled (SPGR) echo pulse sequence (e.g., volumetric interpolated breath-hold examination [VIBE]) more recently enables whole-liver coverage with a short temporal footprint. Further developments of this sequence type showed that 3D spoiled gradient echo acquisition schemes without spectral fat saturation can be used to obtain high-resolution data sets of T1-weighted IP and OP imaging, which allow calculation of fat-only and water-only data sets using Dixon methods of data summation or subtraction, respectively.111,164,222 Diffusion-weighted imaging. Over the past decade, DWI has become a routine component of liver MR sequence protocols. DWI offers information based on hepatic water proton movements, which complements the morphologic information obtained with conventional MRI. DWI is routinely adopted either to detect or characterize hepatic disease, both benign and malignant hepatic lesions, with robust data showing the usefulness of this technique.19 DWI is carried out by supplying sequences with additional gradients implemented during the acquisition. Speciically, T2-weighted sequences, compared with conventional spin echo sequences, have an additional symmetric pair of diffusion-sensitive gradients that are routinely employed. As a result of the irst diffusion gradient, water protons undergo an initial phase shift. This shift will be completely rephased by the second diffusion gradient, without the remaining net phase shift present for protons showing restricted diffusion. By comparison, water molecules without substantial diffusion restriction acquire different phase information between the irst and second gradient; their signal will not be completely rephased by the second gradient, thus leading to a signal loss.19 The degree of water motion has been found to be inversely related to the degree of signal attenuation. The sensitivity of the DWI sequence to water motion can be varied by changing the amplitude of the diffusion-weighted gradient, the duration of the applied gradient, and the time interval between the paired gradients. These variations in gradient characteristics are expressed in one numeric parameter generally referred to as the b value. In everyday clinical practice the diffusion sensitivity can be modiied by changing the b value, which is usually given in seconds per square millimeter. When the b value is changed, usually the gradient amplitude rather than the duration or time intervals between gradients is altered. For example, hepatic hemangiomas or cysts appear hyperintense on standard T2-weighted images and may also appear hyperintense on DWI, because the sequences are based on T2-weighted spin echo sequence designs (so-called T2 shine-through effect) (Fig. 43-6). To eliminate the impact of T1, T2, TR, and TE, apparent diffusion coeficient (ADC) maps can be calculated to obtain pure diffusion information. To calculate ADC maps for each pixel in a DWI series, at least two DWI data sets with differing b values (usually one b value in the range of 0-100 and a second b value ≥400) are postprocessed. The ADC maps represent grayscale-encoded ratios of logarithmized differences in signal intensities as well as differences in b values of the two sequential DWI sequences. Areas of true restricted diffusion demonstrate high signal intensity on DWI, with corresponding low signal intensity on the ADC map. Areas of relatively free diffusion also appear hyperintense on DWI, corresponding to T2 shine-through effects, but will remain hyperintense on the ADC map.19 MRI elastography. Accumulating evidence has shown that measurements of elasticity of liver parenchyma show a strong correlation with degree of hepatic ibrosis.71 Initially this theoretic concept was exploited by ultrasonography-based imaging techniques, where

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A

B

C FIG 43-5 T1-weighted contrast-enhanced MRIs of the liver in a 61-year-old man, showing early arterial (A), midarterial (B), and late arterial (C) phases of DCE hepatic imaging.

A

B FIG 43-6 MRI of the liver for suspected hepatic lesions in a 46-year-old woman. DWI obtained with a b value of 50 (A) and corresponding ADC maps (B) allow for conidently posing a diagnosis of nonenhancing hepatic cyst (arrow).

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Liver: Normal Anatomy, Imaging Techniques, and Diffuse Diseases

external compressional impulses are visualized with Doppler ultrasonography as shear-wave transients propagating through liver parenchyma and directly depending on the elasticity of liver parenchyma itself.71 By comparison, MRI elastography techniques combine the application to the liver parenchyma of an external sinusoidal vibration, with a 2D gradient echo MR elastography sequence. The latter applies motion-encoding gradients along the section-selection direction to detect cyclic motion in the through-plane direction, ensuing in colorcoded maps representing regional elastic properties of the liver parenchyma.19

MRI Sequences. Numerous available MR imagers operating at magnetic low ield strengths of 0.5 T, midield strengths of 1.5 T, and high strengths of 3 T operate a variety of vendor-speciic imaging sequences based on the prior introduced basic MR acquisition schemes. Attempts to unify at least the terminology of MR sequences and parameters have been unsuccessful up to now, and so has the ability to reproduce comparable and clearly manageable listings of sequence chronologies for dedicated MR examinations. The advent of parallel imaging capabilities and subsequent multichannel technologies of receiver coils have further complicated this endeavor. Despite these complicating factors, we intend to include a potpourri of MR sequences and their parameters, which allow a comprehensive hepatic MR workup in a time frame of less than 20 minutes. This imaging protocol includes IP, OP, water-only, and fat-only T1-weighted imaging of the entire liver in one breath hold, respiratorytriggered T2-weighted imaging using fat-suppressed T2-weighted and high-resolution 3D MRCP sequences, and contrast-enhanced fatsaturated T1-weighted imaging with three arterial perfusion phases acquired during one breath hold, one portal venous phase, and one equilibrium phase after administration of a biliary excreted gadoliniumbased contrast agent. Delayed hepatic imaging can be performed optionally 2 hours after initial contrast application (Fig. 43-7). Table 43-7 is a comprehensive fast liver MRI protocol optimized for 3-T scanners.

DIFFUSE PARENCHYMAL DISEASES OF THE LIVER The liver plays several complex roles in the metabolism of amino acids, carbohydrates, and lipids, as well as in the synthesis of a multitude of proteins. The liver is also one of the key organs in the multifarious systems of hematologic coagulation and biliary recycling. The basic pathophysiology of all diffuse parenchymal hepatic diseases is a failure in one of the pathways of these complex hepatic metabolic functions. A wide spectrum of extrinsic agents, organisms, viruses, and intrinsic factors (e.g., enzyme defects, disorders of arterial or portal venous supply and hepatic venous drainage, primary speciic inlammatory processes) have been identiied as activators, catalysts, or triggers of diffuse parenchymal diseases of the liver. Patients’ medical history and hepatic laboratory results derive from these hepatic disturbances and subsequent impairments; hepatic MDCT and MRI can help substantiate clinical diagnoses and verify success of treatment regimens. Depending on the predominant pathophysiologic processes, the diffuse parenchymal hepatic diseases discussed in this chapter have been categorized as storage diseases, vascular diseases, inlammatory parenchymal diseases, and cirrhosis.

Storage Diseases Fatty Liver Disease. Hepatic steatosis is the result of excessive accumulation of triglycerides within hepatocytes, a phenomenon that can affect hepatic parenchyma focally or diffusely. On a cellular level, three

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pathophysiologic phenomena have been identiied that contribute to fatty iniltration of liver parenchyma: decreased mitochondrial fatty acid β-oxidation, increased endogenous fatty acid synthesis or enhanced alimentary delivery of fatty acids, and deicient incorporation or export of triglycerides as very low-density lipoproteins (VLDL).2,3,46 Fatty liver disease can cover a spectrum from dormant noninlammatory fatty liver, termed steatosis, to steatohepatitis with inlammation, ibrosis, and eventually cirrhosis. The term alcohol-related fatty liver denotes fatty liver disease with its entire spectrum of dormant to active inlammatory variants associated with alcohol use—as little as 300 mL ingested per week. In the absence of alcohol consumption, nonalcoholic fatty liver disease (NAFLD) is most commonly associated with obesity, type 2 diabetes mellitus, and dyslipidemia. It can present with an aggressive subtype called nonalcoholic steatohepatitis (NASH), characterized by hepatocyte ballooning and necrosis with and without Mallory’s hyaline and ibrosis. Several other clinical disorders and scenarios including malnutrition, severe hepatitis, corticosteroid use, pregnancy, drug toxicity, malaria, kwashiorkor, Reye’s syndrome, and chemotherapy can also lead to fatty liver disease.5,27,39,176 On unenhanced hepatic MDCT, fatty iniltration results in lowering of the attenuation of the liver parenchyma. In normal adults the attenuation value of the liver is consistently higher than that of the spleen, with a mean difference of 8 HUs.121,160,195 Mild degrees of diffuse fatty iniltration can be diagnosed when the attenuation value of liver parenchyma is less than that of the spleen. Marked steatosis hepatis leads to a characteristic MDCT appearance in which the attenuation of the liver is even lower than that of the blood vessels, in particular the central portal venous branches and IVC. Although fatty iniltration can be depicted on contrast-enhanced MDCT examinations, contrasted images are less reliable and less speciic for detecting steatosis hepatis. Following contrast administration, signiicant fatty iniltration can be suggested if liver attenuation is less than that of muscle. Both focal fatty iniltration and residual foci of unaffected liver parenchyma surrounded by fatty iniltration (fatty sparing) may be confused with neoplastic lesions on MDCT examinations: • Focal fatty iniltration commonly has a segmental or lobar distribution, often with a straight-line margin providing a clue to diagnosis. These large and often irregular-shaped lesions typically extend to the liver capsule, usually without associated bulging of the liver contour. In addition, vessels coursing through the area of abnormality are not displaced. Common locations for nodular fatty iniltration are in the anterior part of segment IV adjacent to the falciform ligament and the issure for the ligamentum teres. • Focal areas of higher attenuation within a region of fatty change can be caused by neoplastic masses as well as regions of fatty sparing. The diagnosis of focal hepatic sparing is suggested when a geographic area of higher attenuation is identiied in a typical location such as along the gallbladder fossa adjacent to the interlobar issure, next to the ligamentum teres, or in a subcapsular location. Dual-energy MDCT is another promising imaging technique for grading fatty changes of the liver. Preliminary experiences have shown that a signiicant correlation exists between fat material density values and amount of fatty deposition69,76,98,153 (Figs. 43-8 to 43-12; see Fig. 43-1). When evaluating the hepatic parenchyma with conventional T1-weighted spin echo sequences, only subtle differences in signal intensity (range, 5%-10%) are seen between physiologic and fatty parenchyma. This difference is only present when affected parenchyma

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A

B

C

D

E

F FIG 43-7 Multiphase contrast-enhanced MRI of the liver using the comprehensive fast liver imaging protocol. Coronal (A) and transverse (B) SSFSE T2-weighted imaging of the entire abdomen. C to F, Parallel precontrast T1-weighted imaging using 3D acquisition schemes with zero-ill interpolation and overlapping thin sections, allowing IP and OP as well as calculation of fat-only and water-only data sets using Dixon methods.

G

H

I

J

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FIG 43-7, cont’d G, Respiratory-triggered T2-weighted STIR sequences are then acquired. H to J, Contrastenhanced hepatic MRI is then performed by initially acquiring hepatic arterial fat-saturated parallel T1-weighted sequences using 3D acquisition schemes in a multiphasic fashion. K, Portal venous-phase T1-weighted imaging follows. A T1-weighted fat-saturated hepatic equilibrium phase (L) is visualized after respiratorytriggered T2-weighted MRCP images (M) are acquired. N, Optionally a delayed T1-weighted fat-saturated imaging sequence can be acquired 2 hours after contrast application.

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TABLE 43-7

Comprehensive Fast Liver MRI Protocol Optimized for 3-T Scanners

Sequence

T2W

T1W IP, OP, Water-Only, Fat-Only

Acquisition scheme Coverage Triggering/breath hold TR TE Pixel bandwidth Slice thickness Field of view Imaging plane

SSFSE

SGE

2D (Non) Breath hold 1339 msec 141.312 msec 325.5 Hz 10 mm 480 mm Transverse and coronal 384 × 128 2 × 20 sec

3D Breath hold

Matrix Acquisition time

T2W Fat-Sat FSE

2D Respiratory triggered 5.026 msec 8571.4 msec 1.336/2.622 msec 90.22 msec 651.1 Hz 244.1 Hz 5 mm 5 mm 340 mm 340 mm Transverse Transverse

320 × 192 24 sec

384 × 224 3-5 min

T1W Fat-Sat T1W Fat-Sat T2W Triple Arterial Portal Venous Fat-Sat Phase Phase MRCP Dynamic SGE multiphase SGE 3D 3D Breath hold Breath hold 3.536 msec 1.72 msec 651 Hz 6 mm 340 mm Transverse

4.364 msec 2.1 msec 244.1 Hz 4.4 mm 340 mm Transverse and coronal 288 × 192 25 sec

256 × 128 3 × 8 sec

T1W Fat-Sat T1W Fat-Sat 2-Hour Delay Equilibrium Phase, Phase Optional

SSFSE

SGE

SGE

3D Respiratory triggered 3529.4 msec 810.92 msec 162.8 Hz 1.6 mm 340 mm Coronal

3D Breath hold

3D Breath hold

4.364 msec 2.1 msec 244.1 Hz 4.4 mm 340 mm Transverse

288 × 288 2-5 min

288 × 192 25 sec

4.364 msec 2.1 msec 244.1 Hz 4.4 mm 340 mm Transverse and coronal 288 × 192 25 sec

Fat-Sat, fat-saturated; FSE, fast-spin echo; IP, in-phase; MRCP, MR cholangiopancreatography; OP, opposed-phase; SGE, spoiled gradient echo; SSFSE, single-shot fast-spin echo; T1W, T1-weighted; T2W, T2-weighted; TE, echo time; TR, repetition time.

A

B FIG 43-8 Geographic fatty iniltration of the liver in this 45-year-old man can be seen on both noncontrast (A) and late hepatic arterial phase (B) images.

contains at least 10% triglycerides. T2-weighted sequences are especially insensitive to diagnose fatty hepatic parenchyma. Gradient echo phase shift imaging, however, has proven to be an excellent tool for differentiating nodular fatty iniltration from neoplasms. Employing IP and OP images, fatty iniltration can be readily diagnosed by comparing signal intensity. On OP images, focal fatty iniltration appears as a region of decreased signal intensity compared to the signal intensity of the corresponding area on the IP image81,108,114,155,158 (Fig. 43-13). In a clinical scenario of a liver lipoma containing only fat, no signiicant changes in signal intensity on IP and OP images occurs; in this clinical situation a fat-suppressed T1-weighted sequence will be able to conirm the diagnosis, showing a signiicant drop in lesional signal intensity.

Hemochromatosis. In HLA-associated inherited primary hemochromatosis, a defect in the intestinal mucosa leads to increased

gastrointestinal resorption of iron despite already adequate iron storage. As a consequence, iron is deposited irst in the hepatocytes and then, as the disease progresses, in other tissues such as the pancreas, gastrointestinal tract, kidneys, heart, joints, and endocrine glands (e.g., pituitary), with resulting destruction of these tissues. Iron is a direct hepatotoxin; subsequent thin ibrous septations develop slowly. The disease usually manifests during the fourth or ifth decade with hepatomegaly, ultimately leading to micronodular cirrhosis of the organ. Clinical symptoms include diabetes, arthralgia, cardiac insuficiency, and hypogonadism. Hepatocellular carcinoma is a late complication and occurs in up to 30% of cases, making it important to diagnose this inherited type of hemochromatosis.12,50 Secondary hemochromatosis presents with the same symptoms but is encountered in patients with chronic anemias who have received multiple blood transfusions. Additional disease forms occur with congenital transferrin deiciency, porphyria cutanea tarda, excessive iron ingestion, and complications of portocaval shunting.91,175

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B

C FIG 43-9 Dual-energy MDCT of the liver in a 65-year-old man with chemotherapy-induced mild liver steatosis. A mild fatty iniltration (arrow) of the left lower lobe can be suspected on conventional imaging (A). The latter suspicion is conirmed by either grayscale (B) or color-coded fat-iodine (C) maps.

FIG 43-10 NCE MDCT shows generalized steatosis hepatis and an area of focal fatty sparing (arrows) in this 42-year-old man. Note the nonobstructing renal stone on the left.

FIG 43-11 NCE MDCT shows focal fatty iniltrations (arrows) in the caudate lobe and hepatocentric and posterior right hepatic lobe in this 59-year-old woman. Note ascites surrounding the liver.

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PART II CT and MR Imaging of the Whole Body As discussed earlier, NCE MDCT at best is able to establish the presence of a hepatic storage abnormality. Differentiating between hemochromatosis, in which there is an iron uptake of the hepatocytes, and hemosiderosis, in which iron is deposited in the Kupffer cells of the hepatic reticuloendothelial system or the splenic monocyte/ macrophages system, is not possible using MDCT alone (Fig. 43-17). Abdominal MRI, on the other hand, is capable of distinguishing these disease entities. In hemosiderosis, low signal intensities are seen in the liver and spleen, similar in appearance to intravenously administered superparamagnetic iron oxide–based contrast agent. In hemochromatosis, hyperintense splenic signal and hypointense pancreatic signal characteristics are observed106,116,174 (Fig. 43-18).

Wilson’s Disease. Impaired biliary excretion of copper and its sub-

FIG 43-12 Contrast-enhanced hepatic MDCT showing histologyproven nonalcoholic steatohepatitis in a 41-year-old man.

Hemochromatosis of the liver can be detected with NCE MDCT, but with moderately limited sensitivity and signiicantly reduced speciicity. Increased attenuation within the hepatic parenchyma to levels in excess of 70 HU on unenhanced MDCT examinations is considered characteristic for iron overload.32,34,68,166 On the other hand, mild forms of iron overload or cases with coexistent steatosis hepatis may appear normal at MDCT. In addition a hyperdense appearance of the hepatic parenchyma is not only seen in hemochromatosis but can also be observed in hemosiderosis, glycogen storage disease, Wilson’s disease with increased copper deposition in the liver and brain, patients with cardiac arrhythmias taking amiodarone, and patients with a history of Thorotrast contrast medium exposure. Also, colloidal gold (used in arthritis treatment) and cisplatin therapy have been reported to increase liver attenuation.42,64,126,156,159,184 MRI has been shown to be signiicantly more sensitive in detecting milder forms of iron storage diseases due to hemochromatosis and has also been proven more speciic than unenhanced MDCT scans. On MRI, affected hepatic parenchyma demonstrates signal reduction due to the paramagnetic effect of the ferric ions, Fe3+, which cause shortening of the T1 and T2 relaxation times of neighboring protons. T2 shortening is the predominant effect and accounts for the reduction in hepatic signal intensity, which is seen best on gradient echo T2-weighted imaging; gradient echo sequences lack the 180-degree refocusing pulse, and Fe3+-induced magnetic inhomogeneities are therefore emphasized. Furthermore, by acquiring multiple T2-weighted sequences with varying TEs, individual T2 relaxation parameters can be calculated and used for evaluation of treatment eficacy25,193 (Figs. 43-14 to 43-16).

Hemosiderosis. Aplastic and hemolytic anemias require frequent blood transfusions, with subsequent increased storage of ferric irons in the liver, spleen, lymph nodes, and bone marrow. Whereas the hepatic iron overload in hemochromatosis leads to increased uptake of iron into the hepatocytes, hemosiderosis is characterized by iron deposition within the reticuloendothelial system. Analogous to hemochromatosis, clinical presentations of hemosiderosis include the inal cirrhotic state of the liver, highlighting the importance of early diagnosis of hemosiderosis and, for treatment options, its correct differentiation from the inherited type of hemochromatosis.

sequent accumulation in tissues, predominantly the liver and basal ganglia, characterizes this autosomal recessive disease, also referred to as hepatolenticular degeneration owing to deposition of copper ions in basal ganglia. Whereas no malignant transformation from hepatic copper deposition to hepatocellular carcinoma is known, Wilson’s disease can present as acute and even fulminant hepatitis with a rapid progression into mostly macronodular-type cirrhosis. Clinically Wilson’s disease presents with very low levels of ceruloplasmin. MDCT imaging demonstrates a nonspeciic hyperdense hepatic attenuation proile due to copper deposition in the liver (Fig. 43-19). As of yet the MRI features of Wilson’s disease do not show characteristic features that distinguish it from other forms of chronic hepatic disease. In clinical scenarios of Wilson’s-induced fulminant hepatitis and subsequent liver failure, early patchy contrast enhancement with signiicantly delayed stromal gadolinium uptake have been observed; however, these are nonspeciic imaging indings.133,178,221 Nevertheless, accumulation of copper ions in the periportal regions and along the hepatic sinusoids may be the hallmark of the hepatic Wilson’s disease, with clinical episodes of acute hepatitis with fatty changes in the liver and periportal inlammation.133,178,221

Reye’s Syndrome. In the pediatric population, fatty degeneration of the liver occurring in concert with an encephalopathy has been described after exposure to inluenza B and varicella viruses and subsequent treatment with acetylsalicylic acid. This treatment causes a limited hepatomegaly with intermittent steatosis hepatis. Clinically the only decisive prognostic indicator is the extent of neurologic symptoms.16,31,38,162 MDCT and MRI of the liver depict mild hepatomegaly with accompanying steatosis hepatis, which are nonspeciic imaging indings (Fig. 43-20).

Glycogen Storage Disease. All known forms of glycogen storage disease are inherited autosomal recessive disorders and are characterized by absence or deiciency of one of the enzymes responsible for producing or metabolizing glycogen. The enzyme deiciency causes either abnormal tissue concentrations of glycogen or abnormally formed glycogen. There are 11 known types of glycogen storage disease involving the liver, musculature, hematopoietic system, myocardium, and kidneys. All known variants of glycogen storage diseases—in particular types Ia (von Gierke’s), Ib, II (Pompe’s), III (Forbes’), and IV (Anderson’s)—as well as VI and IX, have the cardinal symptom of hepatomegaly. Types Ia and Ib have the potential to undergo malignant transformation to form hepatocellular carcinomas, whereas types III and IV progress to develop cirrhosis. In types Ia, Ib, and III an increased incidence of hepatic adenomas has been observed.143,167 Extrahepatic indings include but are not limited to glomerulonephritis, amyloidosis, hypoglycemia, and osteoporosis (types Ia and Ib) as well as

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FIG 43-13 Hepatic MRI shows diffuse steatosis hepatis, predominantly in the right lobe, in this 66-year-old woman. Note the dropout of hepatic signal intensity on OP imaging (A) compared to IP imaging (B). Fat-only (C) and water-only (D) imaging reemphasize the fatty iniltration.

myocardial (types II and IV) and striated muscular insuficiency/ weakness (type III). In all children in whom hepatomegaly is detected in combination with hypoglycemia, growth retardation, a disproportional distribution of body fat, and increased transaminases, the diagnosis of glycogen storage disease should be considered (Figs. 43-21 and 43-22).

Galactosemia and Hereditary Tyrosinemia. Infants with an inherited autosomal recessive defect in the enzyme galactose 1-phosphate uridyltransferase present with clinical symptoms such as growth retardation, nausea, vomiting, diarrhea, and jaundice, usually after their irst exposure to galactose in milk. Delayed symptoms include lethargy, irritability, and convulsions. Subtypes of galactosemia have been identiied and are based on deiciencies of galactose kinase and galactose 6-phosphate epimerase.86,186 Initial imaging indings of cirrhotic changes on hepatic MRI within 6 months after onset of symptoms have to be considered an already

advanced stage of the disease. Extrahepatic manifestations include mental retardation, cataract formation, ascites, and renal failure. Hereditary tyrosinemia, also referred to as tyrosinosis, is an autosomal recessive enzymatic disorder that causes progressive liver disease with either micro- or macronodular cirrhosis. Patients with cirrhosis due to tyrosinemia may display high-attenuating hepatic nodules that may be challenging to differentiate from hepatocellular carcinoma lesions.41

Lipid Storage Disease and Mucopolysaccharidoses. The spectrum of lipid storage disorders subsumes a diverse family of individual diseases related by their molecular pathology, in particular an enzymatic deiciency of a lysosomal hydrolase. This enzymatic deiciency leads to lysosomal accumulation of the enzyme’s speciic substrate, sphingolipid. Because glycosphingolipids are one of the essential components of all cell membranes, they can be found ubiquitously throughout the human body. The inability to properly

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FIG 43-15 T2-weighted hepatic imaging using SSFSE acquisition with FIG 43-14 T2-weighted hepatic imaging using SSFSE acquisition and

a long echo train shows hemochromatosis in this 33-year-old man.

a sparse k-space sampling shows hemochromatosis in this 29-year-old woman. Note Gamna-Gandy bodies in the spleen.

FIG 43-17 NCE MDCT in a 45-year-old man with hemolytic anemia FIG 43-16 T2-weighted hepatic imaging using STIR sequence shows

who required frequent blood transfusions and subsequently developed hemosiderosis.

hemochromatosis in this 39-year-old man.

A

B FIG 43-18 Hemosiderosis in a 51-year-old woman as seen on precontrast T1-weighted hepatic images using OP (A) and IP (B) imaging. Note the dropout of hepatic signal intensity due to induced magnetic ield inhomogeneities in the sequence with the longer TE.

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FIG 43-21 Contrast-enhanced MDCT in an 11-year-old girl with glycogen storage disease type Ia (von Gierke’s disease). Note the round hepatic adenoma in the left hepatic lobe.

FIG 43-19 NCE MDCT in a 41-year-old man with histology-proven Wilson’s disease.

FIG 43-22 Contrast-enhanced hepatic MRI in a 12-year-old girl with glycogen storage disease type III (Forbes’ disease). Note the small round hepatic adenoma in the right hepatic lobe.

FIG 43-20 Contrast-enhanced MDCT in a 10-year-old boy with Reye’s syndrome.

degrade glycosphingolipids leads to pathologic accumulation of enzymatic substrates, resulting in micropathologic and morphologic alterations that have characteristic clinical manifestations. Sphingolipid substrate storage in visceral cells can lead to organomegaly, skeletal abnormalities, and inlammatory iniltrations. The main target organ, however, is the central nervous system, which is responsible for the predominantly neurodegenerative course of lipid storage diseases. Depending on the enzymatic deiciency, the following subtypes of lipid storage diseases have been identiied: GM1 gangliosidosis (β-galactosidase), GM2 gangliosidosis (β-hexosaminidase), Gaucher’s disease (glucocerebrosidase), Niemann-Pick’s disease (sphingomyelinase), Fabry’s disease (α-galactosidase A), Schindler’s disease (αgalactosidase B), metachromatic leukodystrophy (arylsulfatase A), Krabbe’s disease (galactosylceramide-β-galactosidase), Farber’s disease (ceramidase), and Wolman’s disease (cholesteryl-ester-hydrolase). In particular Gaucher’s disease, Niemann-Pick’s disease, Farber’s disease, Wolman’s disease and the gangliosidoses present with an enlarged liver

due to lipid and cholesterol deposition, which leads to cirrhosis and chronic liver failure before adulthood.1,26,28,29,51,60,137,210 MDCT and MRI of the liver show hepatomegaly with accompanying steatosis hepatis as nonspeciic imaging indings (Fig. 43-23). Deicient activity of the enzymes regulating catabolism of glucosaminoglycans leads to accumulation of excess mucopolysaccharides in the somatic and visceral tissues, as well as excretion of speciic metabolites in the urine. In addition to mucopolysaccharides, gangliosides also accumulate. Of the mucopolysaccharidoses, type I (Hurler’s), type II (Hunter’s), type III (Sanilippo’s), type IV (Maroteaux-Lamy), and type VIIb have hepatic manifestations. Clinically hepatomegaly, diffuse ibrosis with heavy deposits of collagen bundles, and microdissection of parenchyma into nodules, as well as micronodular or macronodular cirrhosis can be observed.14,226 MDCT and MRI of the liver show cirrhotic changes, a nonspeciic imaging inding (Fig. 43-24).

Amyloidosis. Diffuse hepatic disease can be seen in either primary or secondary amyloidosis, which in both cases ensues in excessive deposition of ibrils of protein-mucopolysaccharide complexes.134 In

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A

B FIG 43-23 Precontrast T1-weighted (A) and T2-weighted (B) hepatic MRIs in a 15-year-old boy with Gaucher’s disease.

A

B

C

D FIG 43-24 Mucopolysaccharidosis type I (Hurler’s syndrome) in a 19-year-old man as seen on precontrast T1-weighted OP (A) and IP (B), as well as contrast-enhanced (C) sequences and T2-weighted (D) hepatic MRI. Note the extended cirrhosis and area of ibrosis (arrows). Ascites and splenomegaly is also present.

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B FIG 43-25 59-year-old male with non-occlusive thrombus in the main portal vein (A) and splenic vein (B) as seen on contrast-enhanced MDCT acquired during the portal venous contrast phase.

primary amyloidotic involvement of the liver, a mild to severe enlargement of the liver is observed owing to deposition of amyloid ibrils along the hepatic sinusoids and within Disse’s spaces.134 By comparison, secondary amyloidosis is often characterized by a relative sparing of sinusoidal spaces, with a more prominent involvement of the hepatic artery walls. In secondary amyloidosis, there is usually a concomitant involvement of the spleen and kidneys that may appear enlarged as well.134

Vascular Diseases Portal Venous Thrombosis—Cavernous Transformation of the Portal Vein. Virchow’s triad deines the three main mechanisms that lead to thrombosis as hypercoagulability, stasis, and disruption of the vascular endothelium. Hypercoagulable states usually result from systemic diseases such polycythemia vera, antithrombin III deiciency, idiopathic thrombocytosis, chronic myeloid leukemia, protein C deiciency, and paroxysmal nocturnal hemoglobinuria. In contrast, portal venous stasis is often due to local abnormalities such as cirrhosis, large hepatocellular carcinoma, and pancreatic carcinoma; it is also a known complication following splenectomy. Similarly, disruption of the portal venous endothelium has been observed in the clinical scenario of sepsis, direct trauma, schistosomiasis, chronic inlammatory bowel disease, pylephlebitis, and as a complication after direct catheterization. Portal venous thrombosis has been described as a transient disease; however, spontaneous revascularization is rare once the intravascular thrombus has reached smaller portal venous branches. If no spontaneous resolution of the intraluminal thrombus occurs, portoportal venous channels may form to maintain portal perfusion. These portal pathways can be found not only in the porta hepatis but also within the liver. In the porta hepatis a mesh of ine to markedly enlarged serpiginous vessels can be observed in place of the occluded main portal vein. Intrahepatic portal venous shunts form, extending from one segmental portal vein to another. Simultaneously, portosystemic collateral channels are forming, suggesting that despite extensive hemodynamic adaptations, portal hypertension is present. Chronic occlusion of the portal vein or one of its main segmental branches may be accompanied by segmental atrophy of the effected hepatic segments as well as compensatory hypertrophy of the other segments. In livers

with preexisting diffuse fatty iniltration, thrombosis of intrahepatic segmental portal venous branches can result in focal fatty sparing, because fat delivery correlates with portal blood low. MDCT and MRI of the liver are both capable of visualizing portal venous thrombosis and cavernous transformations of the portal vein during the portal venous contrast phase. Furthermore these crosssectional imaging modalities can contribute to the planning of shunt surgery and monitoring of shunt patency in a clinical setting of portal venous thrombosis. In rare cases, cavernous transformation of the portal vein can appear as a subhepatic spongelike mass. This appearance has also been reported in cases of pancreatic hemangiosarcoma and bile duct varices. Hepatic MRI with multiple arterial and portal venous contrast phase acquisitions in combination with biliary high-resolution MRCP imaging will contribute important information in the diagnostic workup. Portal vein patency can be conirmed or excluded by acquiring low-sensitive gradient echo sequences such as steady state with free precession6,44,49,89,115,122,149,183,199,207 (Figs. 43-25 to 43-28).

Obstruction of Smaller Portal Venous Branches. Thrombosis and subsequent ibrosis of smaller portal venous branches can result from hepatopedal extension from an existing portal venous thrombosis. Isolated peripheral occlusions of smaller portal venous branches have been reported to occur in systemic diseases of vasculitic and rheumatoid origin and are an early manifestation of primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and sarcoidosis. Thrombosis of smaller portal venous branches as a complication of a local inlammatory process can occur in the clinical scenario of schistosomiasis.4,45,93,117,146,163,229 Analogous to imaging of portal venous thrombosis and cavernous transformation of the portal vein, hepatic MDCT and MRI to detect thrombosis and subsequent ibrosis of smaller portal venous branches is best achieved during the portal venous perfusion phase (Figs. 43-29 and 43-30).

Portal Venous Air. Portal venous air is recognized not as a speciic disease entity but as a diagnostic clue in patients with acute abdominal pathology. The pathogenesis of this imaging sign is still not fully understood.

A

B FIG 43-26 Contrast-enhanced fat-saturated T1-weighted MRI in a 62-year-old woman with near-occlusive thrombus in the main portal vein (arrow in A). Note the layering phenomenon/low-void artifacts of the intraluminal thrombus formation (arrow in B).

FIG 43-28 62-year-old male with mass-like cavernous transformation FIG 43-27 Contrast-enhanced MDCT acquired during the portal venous contrast phase shows cavernous transformation of the portal vein following long-standing portal venous thrombosis in this 49-year-old man. Ascites and status post splenectomy are also present.

of the portal vein following long-standing portal venous thrombosis (arrows) as seen on contrast-enhanced fat-saturated T1-weighted MRI. Note the low void artifacts within the mass-like cavernous transformation (arrowhead).

FIG 43-29 Contrast-enhanced MDCT acquired during the portal venous

FIG 43-30 Contrast-enhanced MDCT acquired during the portal venous

contrast phase shows thrombosis of the right posterior portal venous branch in this 41-year-old man.

contrast phase shows thrombosis of one of the distal portal venous branches off the right anterior portal vein following cholecystectomy in this 43-year-old woman.

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Two possible pathophysiologic mechanisms have been proposed. According to the irst theory, portal venous air can be found after breakdown of the mucosal lining of bowel in concert with increased barometric and luid pressure in the bowel lumen. In this scenario the gas seen in pneumatosis intestinalis rises through the venous intestinal arcades and mesenteric veins cranially to reach the portal conluence. Within the liver the gas is transported to the small peripheral branches of the subsegmental portal veins by hepatofugal portal venous blood low. The second theory is based on the presence of gas-forming bacteria in the intestinal venous and portal venous systems. Cranial ascension of the intravascular gas ceases in the most cranially located peripheral branches of the subsegmental portal veins. Portal venous air, usually visualized as branching lucencies or susceptibility artifacts located within 2 cm of the liver capsule on MDCT and MR, has to be distinguished from biliary gas. Gas within the biliary tree is usually found within the central portions of the liver, more than 2 cm distant from the liver capsule because of the hepatocentric low of bile. A wide variety of underlying diseases have been identiied as presenting with portal venous air; it has been described in clinical scenarios of gastric ulcers, ulcerative colitis, Crohn’s disease, a complication of endoscopic procedures, intestinal abscesses and tumors, following umbilical vein catheterization, diverticulitis, intraabdominal sepsis, pneumatosis intestinalis, hemorrhagic pancreatitis, superior mesenteric artery thrombosis with subsequent intestinal ischemia, intestinal volvulus, necrotizing gastritis, colonic istulas, enteric necrosis and radiation-induced vasculitis. Most frequently, portal venous gas is caused by mesenteric vascular occlusion and subsequent bowel necrosis, and therefore it is considered an ominous sign with an overall high mortality of up to 75%. For the remaining wide spectrum of possible underlying diseases, however, the mortality drops to 39%.79,103,118,154,179 Detection of portal venous gas on MDCT imaging usually does not pose diagnostic dificulties. On hepatic MRI, however, the air-induced susceptibility artifacts have to be distinguished from vascular low voids and possible intrahepatic calciications. T1-weighted sequences acquired with different TEs will help improve diagnostic precision because the size of air-induced susceptibility artifacts increases with longer TEs (Figs. 43-31 to 43-34).

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Budd-Chiari Syndrome. The classic Budd-Chiari syndrome was described in 1845 as a combination of portal venous hypertension and hepatomegaly due to an obstruction of hepatic venous drainage. The initiating factor of Budd-Chiari syndrome is an obstruction of venous outlow from the sinusoidal bed of the liver, with subsequent development of slowly increasing portal venous hypertension. Only in rare cases does this lead to fulminant liver failure and hepatic encephalopathy. Budd-Chiari syndrome type I involves occlusion of the IVC, with or without secondary occlusion of the hepatic veins; type II consists of occlusion of the major hepatic veins; and type III is venoocclusive disease of the liver, or a progressive thrombotic occlusion of small centrilobular veins. Stasis of the hepatic venous outlow may be related to a membranous obstruction of the IVC, constrictive pericarditis, atrial myxoma, cardiac insuficiency, Hodgkin’s disease, cirrhosis, hepatocellular carcinoma, hematoma or abscess, and adrenal or renal carcinomas. Other contributing factors that are not speciic to hepatic diseases include hypercoagulability and vascular injury as identiied in Virchow’s triad.

FIG 43-32 Contrast-enhanced MDCT acquired during the portal venous contrast phase shows air within the main portal vein (arrow) as well as gastric intramural air (arrowheads) in this 65-year-old man.

FIG 43-33 Contrast-enhanced MDCT acquired during the portal venous FIG 43-31 Contrast-enhanced MDCT acquired during the portal venous contrast phase shows air within the main portal vein (arrow) in this 67-year-old woman.

contrast phase shows air within the medial and lateral branches of the left portal vein (arrow) as well as gastric intramural air (arrowheads) in this 55-year-old man.

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The role of MDCT and MRI of the liver in the speciic settings of suspected conirmed or treated Budd-Chiari syndrome includes identiication of vascular anatomy, detection of intrahepatic or extrahepatic masses, parenchymal evaluation, and assessment of shunt patencies in cavoatrial, mesocaval, and mesoatrial vascular bypasses. Cross-sectional imaging modalities are able to quantify any reduction in vascular caliber of the hepatic veins or detect missing connections to the IVC or their complete absence. In addition they allow depiction of newly formed but less competent intrahepatic collateral veins. Alteration of venous drainage ultimately leads to peripheral atrophy of hepatic parenchyma and an atypical parenchymal enhancement. Compensatory hypertrophy of both central parenchymal segments and the caudate lobe—which have improved venous drainage and different vascular anatomy, respectively—can be observed. In patients with polycythemia vera or paroxysmal nocturnal hemoglobinuria as a

reason for their hypercoagulable state, the indings of diffusely increased red bone marrow/splenomegaly or increased renal parenchymal density/decreased intensity on T1-weighted sequences, respectively, are typical cross-sectional imaging characteristics. Invasive treatment options include redirection of either hepatic venous or portal venous blood in an effort to decrease liver congestion or portal hypertension, respectively. Cavoatrial shunts redirect blood low directly into the right atrium in clinical scenarios of solitary occlusion of the IVC. Mesocaval shunts lower the pressure in the portal venous system by bypassing the solitarily occluded hepatic vein, connecting the superior mesenteric vein to the IVC. Finally, mesoatrial shunts bypass thrombosed or occluded hepatic veins and the IVC to redirect blood low from the superior mesenteric vein to the right atrium. MDCT allows direct visualization of the thrombi that can occlude or narrow the shunts, whereas hepatic MRI low-void analysis and phase-contrast angiography techniques allow depiction and quantiication of low, including detection of low reversal8,96,128,130,140,185,191,213,217 (Figs. 43-35 and 43-36).

Hepatic Venoocclusive Disease. Thrombotic and subsequent

FIG 43-34 Contrast-enhanced MDCT acquired during the portal venous contrast phase shows air within one of the venous branches of the superior mesenteric vein (arrows) in a clinical scenario of pneumatosis intestinalis in a 79-year-old man.

A

ibrotic obstruction of submillimeter hepatic veins initially leads to congestion of the sinusoids, with resultant hepatomegaly. Eventually ibrosis of the liver will occur. Medications and treatments associated with bone marrow transplantation (e.g., azathioprine, pyrrolizidine alkaloids, cysteamine, whole-body radiation) are known to induce hepatic venoocclusive disease. Distinguishing hepatic venoocclusive disease from Budd-Chiari syndrome types I and II is a key point because in venoocclusive disease the IVC and main hepatic veins are patent, but the terminal hepatic venules and sinusoids are partially or entirely destroyed. In comparison to Budd-Chiari syndrome, hepatic venoocclusive disease is associated with early-stage liver failure with jaundice and thrombocytopenia. DCE MRI may indicate increased arterial perfusion of the affected hepatic segments as well as a prolonged liver transit time of the contrast agent. However, conirmation of the diagnosis should be attempted with direct histopathologic examination or direct wedge hepatic venography.24,192,203 In the context of the hepatic venoocclusive disease spectrum, chronic graft-versus-host liver disease and liver allograft rejection should be mentioned. Owing to a substantial overlap in imaging

B FIG 43-35 Contrast-enhanced MDCT acquired during the portal venous contrast phase in a 77-year-old man with acute Budd-Chiari syndrome (A) in combination with acute thrombosis of the portal vein (arrow in B).

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A

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B

C FIG 43-36 Chronic Budd-Chiari syndrome in a 65-year-old woman as seen on T2-weighted (A), precontrast T1-weighted (B), and contrast-enhanced fat-saturated T1-weighted (C) hepatic MRI acquired during the portal venous contrast phase.

indings, both clinical history and pathology are of paramount importance for making a differential diagnosis among these entities196 (Fig. 43-37).

Liver Disease in Congestive Heart Failure. Hepatic congestion due to chronic failure of the right heart leads to widening and splaying of the central hepatic veins and overall hepatomegaly. The combination of decreased venous blood low, increased blood pressure, and hypoxemia leads to diffuse cellular necrosis. Long-standing diffuse cellular necrosis induces diffuse hepatic ibrosis with a micronodular cirrhotic pattern known as nutmeg liver. Macroscopically, hepatic MDCT and MRI are able to depict cirrhotic changes as a nonspeciic imaging inding, but microscopically the hepatic architecture remains intact77,100,132,144 (Fig. 43-38).

Hepatic Arterial Obstruction. In comparison to portal venous or

FIG 43-37 T2-weighted hepatic MRI shows hepatic venoocclusive

hepatic venous obstruction or occlusion, signiicant stenosis or occlusion of the hepatic arteries is a much rarer entity, commonly associated

disease following treatment with pyrrolizidine alkaloids in this 61-yearold woman. Note the mild hepatomegaly.

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A

B FIG 43-38 Contrast-enhanced MDCT shows a hemodynamic-relevant right cardiac mass (arrows in A) leading to enlargement of the suprahepatic inferior vena cava, as well as hepatic congestion (B), in this 59-year-old man.

with liver transplantation. The arterial anastomosis of the donor liver to the native vessel trunk can initially be signiicantly narrowed and subsequently thrombose because of the changes in hemodynamic low. In patients without prior liver transplantation, an embolic occlusion is the most common cause of hepatic arterial compromise. The hepatic artery constitutes approximately 25% of the blood low to the liver, supplying mainly the endothelial lining of the intrahepatic bile ducts and the ibrous hepatic structures. Contrast-enhanced MDCT and MRI show a diffusely diminished enhancement of the hepatic parenchyma in cases of severe hepatic artery stenosis or occlusion. High-resolution MDCT and MRI of the porta hepatis can identify the exact location of the culprit intraluminal thrombus or stenosis20,22,85,127,202 (Fig. 43-39).

Intrahepatic Arteriovenous Fistulas—Intrahepatic Shunts. Intrahepatic arteriovenous istulas can occur as vascular connections between hepatic arteries and hepatic veins, as well as between hepatic arteries and the portal venous system. A diffuse intrahepatic distribution is seen with hereditary hemorrhagic telangiectasia, also known as Osler’s disease; solitary occurrences of arteriovenous istulas are most often related to liver biopsies or surgical procedures. In Osler’s disease an enlarged hepatic artery is usually seen in combination with tortuous vasculature in the porta hepatis. Functionally the increased arterial perfusion of the liver tissue leads to a secondary hypertrophy. Severe cases of Osler’s disease can subsequently lead to right-sided cardiac failure. In solitary iatrogenic postprocedural intrahepatic arteriovenous istulas, there is signiicant dilatation of the draining vein. In the case of a vascular connection between hepatic arteries and the portal venous system, the resultant increased portal venous pressure leads to signs of portal venous hypertension and oftentimes reversed low in the affected portal venous branch. Both MDCT and DCE MRI are capable of depicting the early venous drainage occurring during the hepatic arterial phase and can help estimate the functional signiicance of the istula15,58,84,168,227 (Figs. 43-40 and 43-41).

FIG 43-39 Contrast-enhanced fat-saturated T1-weighted MRI in a 41-year-old man status post liver transplant shows occlusive thrombus formation within the hepatic artery at the level of the vascular anastomosis (arrow) and subsequent development of left hepatic cholangitis.

Liver Infarction. Hepatic infarction is rare, in large part because of the dual-source blood supply provided by the hepatic artery and portal vein. Signiicant infarcts of hepatic parenchyma are therefore only possible if both sources of hepatic blood supply are signiicantly compromised, as in acute shock trauma and hypercoagulability and in clinical scenarios such as preeclampsia or postpartum patients with HELLP syndrome (hemolytic anemia, elevated liver enzymes, low platelets). A particular variant of hepatic ischemia is pseudoinfarction of the liver, also referred to as a Zahn infarct, consisting of an area of congestion with parenchymal atrophy but without necrosis, usually due to obstruction of a branch of the portal vein. Zahn infarcts are unique in that there is collateral congestion of liver sinusoids that does not include areas of anoxia seen in most infarcts. Fibrotic tissue may develop in the area of the infarct.

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The typical MDCT appearance of liver infarction is a peripheral wedge-shaped area of low attenuation on contrast-enhanced MDCT. Larger infarcts may have a more geographic distribution. At MRI, lesions are typically hypointense on T1-weighted images but hyperintense on T2-weighted images. Although the diagnosis of liver infarction is evident in most cases, it may be confused with focal fatty iniltration, abscess, or even a tumor. It is of note that hepatic infarction does not demonstrate either mass effect or increased contrast enhancement. Also, vessels coursing through the lesion, although typically seen in focal fatty iniltration, are usually not seen in hepatic infarction62,75,109,113,187,230 (Figs. 43-42 to 43-44).

Liver Trauma. In acceleration/deceleration traumas such as motor

FIG 43-40 Contrast-enhanced fat-saturated T1-weighted hepatic MRI shows an intrahepatic istula (arrow) between a right posterior portal venous branch and a hepatic venous branch draining into the inferior vena cava (arrowheads) in this 54-year-old woman.

A

vehicle accidents and direct penetrating traumas of the abdomen, the liver and spleen are the most frequently injured organs. Traumatization of the liver and spleen is often associated with an overall unstable hemodynamic situation. The right hepatic lobe is most commonly affected, with subcapsular hematoma formation and direct parenchymal compression, parenchymal contusions or lacerations, or rupture of the biliary tree with subsequent formation of bilomas.

B FIG 43-41 Contrast-enhanced fat-saturated T1-weighted hepatic MRI in a 44-year-old man shows intrahepatic istulas between the right hepatic arterial branches (arrow in A) and portal venous branches, with early contrast enhancement of the portal vein (arrows in B) during the arterial contrast phase.

A

B FIG 43-42 Acute infarction of the liver parenchyma in a 78-year-old man as seen on contrast-enhanced MDCT (arrows in A) and T2-weighted hepatic MRI (arrows in B).

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A

B FIG 43-43 Chronic infarction and subsequent atrophy of the liver parenchyma in a 69-year-old man as seen on contrast-enhanced MDCT (arrows in A) and T2-weighted hepatic MRI (arrows in B).

A

B FIG 43-44 This 72-year-old woman had multiorgan failure and infarctions involving liver, spleen, and bilateral kidneys.

Hemorrhage into the biliary tree can be identiied due to the typical imaging appearance of blood on MDCT and MRI. Multiplanar reformations of high-resolution, cross-sectional imaging data sets are essential to detect complex parenchymal injuries, in particular parenchymal tears originating in the region of the bare area can be dificult to detect, as they follow the hepatic venous distribution7,30,104,110,148 (Fig. 43-45).

Inlammatory Parenchymal Diseases and Cirrhosis Viral Hepatitis. The histopathologic patterns of hepatitides of various causes show cellular alterations with differing penetration of periportal hepatocellular necrosis, Kupffer cell mobilization, and portal inlammation of plasma cells, depending on the underlying infectious, toxic, or autoimmune etiology. Inlammatory conditions of the hepatic parenchyma can be self-limiting, progress to scarring of liver segments, or end in an overall cirrhotic state. The acute form of hepatitis lasts less than 6 months; chronic hepatitis is deined as any inlammatory condition of the hepatic parenchyma that does not show signs of regression for time periods longer than 6 months.

Viral hepatitides are still the most common causes of liver disease worldwide. Six hepatotropic viruses, in particular picornavirus (hepatitis A), hepadnavirus (hepatitis B), lavivirus (hepatitis C), hepatitis-E virus, togavirus (hepatitis F), and GBV-C (hepatitis G) have been identiied. The acute forms of viral hepatitis usually cause hepatomegaly with an edematous liver capsule and distinct necrotic areas that result in irregularities of the liver contour. In its fulminant presentation, acute hepatitis causes extensive necrosis that leads to shrinkage of the entire organ and signiicant loss of parenchymal volume. Necrotic areas transform into scars during the phase of restitution, which can take on an imaging appearance similar to cirrhotic liver segments. Chronic hepatitis is a necroinlammatory condition dominated by lymphocytes. Long-standing edema of the hepatic parenchyma progresses to heterogeneous patterns of inlammation and hepatocyte regeneration, with subsequent ibrosis and possible cirrhosis of the liver. Ascites and splenomegaly can accompany any state of chronic hepatitis.

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A

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B

C FIG 43-45 Contrast-enhanced MDCT during the portal venous contrast phase shows hepatic trauma with differing degrees of parenchymal injury. A, A 19-year-old man with laceration of the posterior liver contour and accompanying subcapsular and extracapsular hematoma. B, A 22-year-old woman with contusion and laceration of the hepatic parenchyma. C, A 29-year-old woman with massive traumatic injury to the hepatic and splenic parenchyma.

Acute and chronic hepatitides are primarily diagnosed by clinical and serologic examinations; hepatic MDCT and MRI can, however, contribute to the diagnosis. In particular these imaging modalities can be used to determine the extent and severity of compromised hepatic parenchyma. MDCT imaging of acute and fulminant courses of hepatitis is capable of identifying general hepatomegaly combined with edema of the liver capsule. Furthermore, NCE MDCT imaging can show heterogeneous attenuation of the hepatic parenchyma, with multifocal or conluent regions in the periphery. Overall hepatic parenchymal attenuation is equal to or less than that of the spleen. Contrast-enhanced MDCT can demonstrate irregular perfusion with heterogeneous attenuation throughout the hepatic parenchyma; nodular areas of regeneration have higher attenuation values compared to surrounding edematous or partially necrotic parenchymal segments. The highly variable MDCT imaging patterns of chronic hepatitis are discussed later with cirrhosis. Hepatic MRI of acute viral hepatitis, analogously to MDCT imaging, shows general hepatomegaly combined with edema of the liver capsule. Additionally, regions of high signal intensity can be seen on T2-weighted image sequences surrounding the portal venous branches. A similar contrast enhancement pattern to that observed on MDCT imaging can be detected on DCE and multiphase contrastenhanced MRI (Fig. 43-46). During the course of chronic hepatitis, signiicant lymph node enlargement can occur, in particularly in the

porta hepatis. As opposed to nodal enlargement caused by metastases, the portal vein remains patent and maintains its shape. MRI patterns of chronic hepatitis are discussed later (see “Cirrhosis—Portal Venous Hypertension”73,87,97,99,129,145,157,214 (Figs. 43-47 and 43-48).

Radiation-Induced Hepatitis. Given the large size and anatomic location of the liver, it is frequently affected by radiation therapy of extrahepatic malignancies. Whereas the histopathologic and MDCT/ MRI indings in radiation-induced hepatitis at least partially overlap with histopathologic analysis and imaging of hepatitides of other causes, the anatomic location and margination of radiation-induced hepatitis within the hepatic parenchyma can help correctly identify this entity. In particular there is often a straight linear margin to the parenchymal abnormality that corresponds to the radiation portal. Reduced portal venous low in areas with radiation injury has been observed as well.59,212,228

Hepatic Sarcoidosis. Noncaseating epithelioid granulomas scattered throughout the liver is the most common hepatic presentation of multisystem sarcoidosis, also known as Boeck’s sarcoid. Although involvement of abdominal organs is frequent, its abdominal manifestations are usually documented after the initial diagnosis has been made based on thoracic indings, namely bihilar lymphadenopathy. The underlying pathophysiology that leads to formation of noncaseating epithelioid granulomas remains unknown, but an association with

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A

B FIG 43-46 Acute viral hepatitis in a 39-year-old man as seen on contrast-enhanced MDCT acquired during the arterial phase (A) and the portal venous phase (B). Note the heterogeneous contrast enhancement in the edematous enlarged liver.

A

B FIG 43-47 Precontrast OP (A) and contrast-enhanced fat-saturated (B) T1-weighted hepatic MRI in a 54-yearold man with chronic viral hepatitis.

primary sclerosing cholangitis and coexistence with a wide range of other autoimmune diseases has been revealed. The most common sites of involvement include the lymph nodes, lungs, liver, spleen, eyes, skin, salivary glands, nervous system, bones, and heart. Hepatic noncaseating epithelioid granulomas present without speciic features and range from submillimeter to 1 to 2 cm in size. Larger granulomas contain greater amounts of reticulin and are surrounded by ibrotic hepatic parenchyma, relecting a more vigorous immunologic response to the unknown causative agent. Acute complications include hepatic failure due to intrahepatic cholestasis and portal hypertension; a multisystem sarcoidosis mortality of 10% has been described and is due to cor pulmonale, lung ibrosis, and liver cirrhosis.56,74,94,171,204

NCE MDCT imaging shows multiple intrahepatic and intrasplenic hypodense lesions accompanied by nonspeciic hepatosplenomegaly. These lesions become rapidly isodense to liver parenchyma after intravenous contrast administration (Figs. 43-49 and 43-50). Hepatic MRI demonstrates the noncaseating epithelioid granulomas as hypointense intrahepatic and intrasplenic nodules on T1- and T2-weighted imaging sequences. Advanced-stage hepatic sarcoidosis may present as liver cirrhosis (Fig. 43-51); MDCT and MRI patterns of cirrhosis are discussed in “Cirrhosis—Portal Venous Hypertension.”

Hepatic Candidiasis. A fungal infection with Candida albicans leads to development of multiple well-deined, rounded intrahepatic

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FIG 43-50 Contrast-enhanced MDCT shows multisystemic sarcoidosis FIG 43-48 Portal venous phase imaging shows heterogeneously enhancing hepatic parenchyma as well as hepatomegaly in a 49-yearold man with acute viral hepatitis.

of the liver and spleen in this 75-year-old man. Note the subtle hepatic lesions (arrow) in contrast to the more clearly seen splenic lesion.

FIG 43-51 Contrast-enhanced MRI in a 64-year-old woman with multisystemic sarcoidosis of the liver and spleen.

FIG 43-49 Contrast-enhanced MDCT shows multisystemic sarcoidosis of the liver and spleen in this 55-year-old man. Note disseminated distribution of innumerable hepatic lesions.

microabscesses. Hepatic candidiasis is a common fungal infection in immunocompromised patients. Candida tropicalis infections are predominantly seen in tropical countries. Hepatic candidiasis results from intrahepatic spread of intestinal fungal seeding via portal venous and hepatic venous circulation of Candida strains. Complications of hepatic candidiasis arise in cases of microabscess rupture and/or accompanying cholangitis. MDCT imaging will reveal innumerable hypodense liver lesions of less than 1 cm in diameter and without contrast enhancement. The intrahepatic periportal ields may show a slight increase in attenuation due to ibrosis. During the healing phase, scattered calciications may be observed (Figs. 43-52 to 43-54). Hepatic MRI will show innumerable small hypointense lesions on T1-weighted imaging sequences, whereas on T2, the same lesions will

be hyperintense. No contrast enhancement is seen within the lesions. T1-weighted gradient echo sequences have shown greater sensitivity in detecting the small hypointense lesions compared to spin echo acquisition schemes.172,173,219

Hepatic Schistosomiasis. Two Schistosoma species, Schistosoma japonicum and Schistosoma mansoni, are held primarily responsible for signiicant hepatic disease. For both species, infections results from water contact that is sustained by free-swimming cercariae burrowing themselves into the skin.142 The organisms thus enter the bloodstream, where they reside for a while to carry out the maturation process for then migrating in the mesenteric-portal venous system.142 Pathologic and imaging indings of hepatic disease by Schistosoma species can be explained by schistosome egg embolization to the terminal venous branches of the portal system, ensuing in chronic granulomatous reaction, extensive ibrosis, and calciication.142

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FIG 43-52 Contrast-enhanced MDCT in a 41-year-old woman with microbiologically proven candidiasis of the liver. Note splenic involvement.

FIG 43-54 Contrast-enhanced MDCT in a 55-year-old woman with microbiologically proven candidiasis. Note disseminated distribution of innumerable submillimeter hepatic and splenic lesions.

FIG 43-55 Contrast-enhanced fat-saturated T1-weighted hepatic MRI FIG 43-53 Contrast-enhanced MDCT in a 49-year-old man with microbiologically proven candidiasis of the liver. Note disseminated distribution of innumerable submillimeter hepatic lesions.

shows peliosis hepatis (arrows) that developed in this 59-year-old woman while she was being treated with tamoxifen.

can show imaging characteristics of blood at different phases of organization53,83,194,209,219 (Figs. 43-55 and 43-56).

Peliosis Hepatis. Microscopically, peliosis hepatis shows dilatation

Cirrhosis—Portal Venous Hypertension

of the sinusoids in concert with multiple blood-illed lacunar spaces. The pathogenesis remains unknown; general outlow obstruction of the sinusoids with breakdown of the sinusoidal barriers has been suggested as an initiating pathomechanism. Agents associated with development of peliosis hepatis are anabolic steroids, corticosteroids, tamoxifen, diethylstilbestrol, azathioprine, and oral contraceptives. Macroscopically, hepatomegaly may be present. Hepatic MDCT shows multiple small hypodense lesions less than 1 cm in diameter on noncontrast images; centrifugal contrast uptake during the portal venous imaging phase can be seen. Thrombosed venous branches remain hypodense during parenchymal phase imaging. Hepatic MRI will reveal small hypointense lesions on T1-weighted imaging sequences, whereas on T2 the same lesions appear hyperintense. Analogous centrifugal contrast uptake is noted. Larger lesions

Cirrhosis as multisystem disease. Liver cirrhosis represents an irreversible hepatic ibrosis bridging the portal tracts. Conditions leading to cirrhosis include chronic hepatitis, alcohol abuse, hemochromatosis, drug toxicity, chronic biliary obstruction as seen in primary sclerosing cholangitis and primary biliary cirrhosis, as well as inlammatory parenchymal processes. If the inciting cause is unknown the process is referred to as cryptogenic cirrhosis. Cirrhosis affects the contour of the organ and the size of the lobes and segments and may cause benign as well as malignant focal lesions to arise within the liver. Processes associated with cirrhosis include ascites and portal hypertension. Splenomegaly in turn is the most common inding of portal hypertension. Another common entity associated with portal venous hypertension are collateral vessels or varices; these can be seen as enhancing tortuous vessels in the paraesophageal and gastric regions, porta

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FIG 43-56 Contrast-enhanced fat-saturated T1-weighted hepatic MRI shows peliosis hepatis (arrows) that developed in this 51-year-old woman while she was being treated with steroids.

hepatis, peritoneal cavity, retroperitoneum, and even coursing through the liver via paraumbilical collaterals. Furthermore, mesenteric, omental, and retroperitoneal edema can be demonstrated in clinical scenarios of cirrhosis. The edema is usually mild but may be severe in approximately 25% of patients. Cirrhosis markedly distorts the hepatic parenchyma, producing either a smooth, nodular, or lobular appearance of the hepatic capsule in the majority of cases. Margins that are either smooth or deformed by multiple small nodules are typically seen in micronodular cirrhosis. These micronodules underlying the surface of the liver are often not visualized at MDCT or MRI. Coarse nodularity of the hepatic margin is the result of macronodular cirrhosis. Tremendous overlap in the frequency of smooth and nodular hepatic morphology among different causes of cirrhosis usually prevents distinguishing the etiology based on imaging appearance. However, a lobular liver margin is more frequently seen in patients with primary sclerosing cholangitis. Adenopathy can be seen in the porta hepatis and peripancreatic region in some cases of cirrhosis. Occasionally these nodes can be large and bulky, mimicking neoplastic involvement. These lymph nodes are most prominent in cases of primary biliary cirrhosis. Fibrosis can appear as a conluent mass replacing the cirrhotic regenerating parenchyma in approximately 30% of patients. Focal conluent ibrosis may be seen in all types of cirrhosis but occurs most commonly in primary sclerosing cholangitis and least commonly in primary biliary cirrhosis. Essential imaging features include focal retraction of the liver capsule over the area of ibrosis and incomplete involvement of liver segments, with accompanying atrophy and characteristic location in segments IVa, IVb, VII, and VIII. Focal conluent hepatic ibrosis appears as a wedge-shaped structure radiating from the porta hepatis. On MDCT and MRI, cirrhosis causes a patchy intrahepatic attenuation or signal intensity in about 65% and a diffusely heterogeneous appearance in another third of patients. Approximately 25% of endstage cirrhotic livers appear normal in size and shape; another third may be diffusely atrophic. The majority of end-stage cirrhotic livers exhibit a combination of segmental hypertrophy and atrophy, with the predominant inding being hypertrophy of liver segments I-III. Focal atrophy is most common in segments IV-VIII and may range from mild to complete involution of the affected segments. Occasionally the segments II/III and VI/VII may be atrophic; this is most often seen in

1301

patients with primary sclerosing cholangitis. Another rare inding in patients with primary sclerosing cholangitis is a higher attenuation in segment I, mimicking a pseudotumor in the caudate lobe.106 Approximately 25% of all patients with end-stage cirrhosis show a heterogeneous appearance in all parts of the liver on unenhanced MDCT and T2-weighted MRI.129 Histopathologic analysis reveals three causes for this appearance: diffuse ibrosis, fat deposition, and iron deposition. On MDCT imaging, four different patterns of diffuse ibrosis may be seen: (1) patchy and poorly deined regions of low attenuation on unenhanced MDCT, (2) thin perilobular bands of low attenuation on unenhanced MDCT, (3) low-attenuation thick ibrotic bridging surrounding regenerative nodules, and (4) diffuse ibrosis causing a highattenuation perivascular cufing. The latter two are most commonly observed in patients with primary biliary cirrhosis. Owing to the reduction in portal venous low in patients with end-stage cirrhosis, contrast-enhanced MDCT during the portal venous phase is usually not helpful in demonstrating ibrosis. On unenhanced MDCT, focal conluent ibrosis most often appears as a lesion with low attenuation. Following contrast medium administration, approximately 50% of the lesions become isoattenuating with the surrounding parenchyma. Contrast enhancement of the ibrotic area may rarely simulate a neoplastic process, which typically requires percutaneous biopsy (Figs. 43-57 to 43-59). On T2-weighted MRI, ibrosis appears as an area of high signal intensity. On unenhanced T1-weighted imaging, ibrosis usually cannot be visualized. Following contrast medium administration, however, in cases with thin perilobular bands or perivenous cufing, the ibrous tissue may show mild enhancement on T1. Focal conluent ibrosis appears bright on T2 and hypointense on T1, with a characteristic enhancement pattern most pronounced on equilibrium phase imaging37,88,90,151,152,182,208,211,218,220 (see Fig. 43-59). Cirrhosis and its hepatospeciic presentation. Another characteristic sign of liver cirrhosis is development of a spectrum of focal liver lesions ranging from benign regenerative nodules to malignant hepatocellular carcinoma. Regenerative nodules are present in all cirrhotic livers; however, these nodules are visualized in only 25% of unenhanced MDCT scans and approximately 50% of MRIs. These nodules usually present as high-attenuation lesions on unenhanced MDCT, owing to their iron and/or glycogen content or simply because they are surrounded by lower-attenuation ibrosis. On portal venous phase contrast-enhanced imaging, these nodules are rarely seen. On MRI these focal lesions can appear hypo-, iso-, or hyperintense on T1-weighted images; an isointense appearance is most common and a hyperintense appearance least common. On T2-weighted images, they typically appear as hypointense nodules; the iron they contain causes local magnetic ield inhomogeneities with decreased liver signal intensity due to shortening of T2 relaxation time (Fig. 43-60). Dysplastic nodules are premalignant lesions that represent an intermediate step in the pathway of hepatocarcinogenesis in cirrhotic livers. These lesions are present in approximately 10% of all end-stage cirrhotic livers. Dysplastic nodules appear slightly hyperdense or isodense on unenhanced MDCT imaging and isodense or hypodense on all contrast-enhanced scans (e.g., arterial phase, portal phase, and delayed scans). On MRI, dysplastic nodules appear hyperintense on T1 and iso- to hypointense on T2 and show varying amounts of contrast uptake213 (Figs. 43-61 and 43-62). The incidence of hepatocellular carcinoma in end-stage cirrhosis is high, ranging from 3% to 11%, most often in cases of cirrhosis caused by hepatitis. Carcinogenesis of hepatocellular tumors changes the Text continued on p. 1306

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A

B

C

D FIG 43-57 Contrast-enhanced MDCT shows the spectrum of appearances of cirrhosis. A, A 51-year-old woman with prominence of the caudate lobe (arrow) and mild cirrhotic nodularity imaged during the arterial contrast phase. B, A 55-year-old woman with splenomegaly (arrows) as sign of portal hypertension, adenopathy (arrowheads), and irregularities of the hepatic contours imaged during the portal venous contrast phase. C, A 61-year-old man with increased nodularity of the hepatic parenchyma imaged during the portal venous contrast phase. D, A 63-year-old man with hepatic atrophy and ascites imaged during a delayed contrast phase.

A

B FIG 43-58 A and B, Contrast-enhanced MDCT during the parenchymal contrast phase shows conluent ibrosis (arrows) within a cirrhotic liver in this 52-year-old woman.

A

B FIG 43-59 Conluent ibrosis (arrows) within the cirrhotic liver of a 69-year-old man as seen on precontrast OP T1w (A) and T2-weighted (B) hepatic MRI.

A

B

C

D

FIG 43-60 Cirrhosis and multiple regenerating nodules dissemi-

E

nated throughout the liver of a 78-year-old man as seen on contrast-enhanced MDCT during the portal venous contrast phase (arrows in A and B) and on hepatic MRI using T2-weighted (C), T1-weighted precontrast (D), and T1-weighted fat-saturated postcontrast (E) sequences. Note the subtle delineation of the regenerating nodules in postcontrast MDCT and T1, the hypointense imaging characteristics on T2, and the lack of contrast uptake on T1 fat-saturated postcontrast sequences.

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A

B

C

D

E

F FIG 43-61 Cirrhosis and a prominent dysplastic nodule in the right hepatic lobe (arrows) of a 79-year-old man as seen on arterial (A) and portal venous (B) MDCT imaging as well as on T2-weighted (C), precontrast T1-weighted (D), fat-saturated early arterial T1-weighted (E), and portal venous T1-weighted (F) hepatic MRI. Note the hypodense to isodense imaging characteristics on MDCT and the hyperintense visualization on precontrast T1-weighted hepatic MRI.

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A

B

C

D

E FIG 43-62 Cirrhosis and dysplastic nodule in the right hepatic lobe (arrows) of a 51-year-old man. T2-weighted (A) hepatic MRI, shows an additional bright central focus suspicious for malignant transformation into a hepatocellular carcinoma, known as nodule-in-nodule sign. Precontrast T1-weighted image (B) shows a hyperintense lesion. Fat-saturated early arterial T1-weighted (C), late arterial (D), and delayed imaging (E) show an initial focal contrast uptake (arrows).

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A

B FIG 43-63 Biopsy-proven hepatocellular carcinoma in the right hepatic lobe (arrows) of a 59-year-old man as seen on arterial (A) and delayed (B) MDCT imaging. Note subtle demarcation of the pseudocapsule on the delayed image.

hemodynamic properties and vascular supply of the tumor nodules, resulting in different enhancement patterns in early and advanced hepatocellular carcinomas. In early hepatocellular carcinoma the combination of reduced hepatic arterial perfusion and preserved portal venous low results in low attenuation on MDCT arteriography and isoattenuation on portal venous MDCT. In advanced hepatocellular carcinoma the combination of neoplastic arterial perfusion induced by mechanisms of angioneogenesis and obliteration of portal veins results in high attenuation on MDCT arteriography and low attenuation on portal venous MDCT. Employing hepatic MRI, various appearances may be seen on T1-weighted imaging, ranging from hypointense to hyperintense lesions. However, almost all hepatocellular carcinomas appear bright on T2, allowing for differentiation of dysplastic nodules from hepatocellular carcinomas. Small hepatocellular carcinomas may be seen on early DCE MRI only, on which they appear as hyperintense enhancing nodules. Another characteristic inding in hepatocellular carcinoma is the presence of a pseudocapsule consisting of connective ibrous tissue that appears hypointense on T1 and T2 sequences. Following administration of contrast agents, this pseudocapsule usually shows early enhancement but becomes more prominent on portal venous phase imaging82,107,119,177,205 (Fig. 43-63; see Fig. 43-62).

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44 Liver: Focal Hepatic Mass Lesions Satoshi Kobayashi and Osamu Matsui

Focal hepatic mass lesions can be divided into: (1) pseudolesions or pseudotumors, (2) nontumorous mass lesions, including cysts and inlammatory masses, (3) benign tumors, and (4) primary and secondary malignant tumors. Ultrasonography plays a primary role in detection of focal hepatic mass lesions; for further characterization, computed tomography (CT) and magnetic resonance imaging (MRI) provide valuable information. This chapter discusses the CT and MRI features of hepatic mass lesions and their pathophysiology.

TYPES OF LESIONS

portion of the portal vein through the peribiliary vascular plexus, the obstructed segment shows early enhancement on dynamic CT and MRI (segmental staining) (Fig. 44-2). This segmental staining is often observed in HCC or other malignant tumors with portal vein invasion and makes it dificult to detect the underlying tumor itself.100,184 When Zahn’s infarction occurs, the obstructed area shows hypodensity on precontrast CT, hypointensity on T1-weighted images, and hyperintensity on T2-weighted images. In a fatty liver this area often demonstrates focal sparing, and the causative disease can be overlooked.61 Intrahepatic hepatic vein obstruction results in similar indings based on the segmental distribution of the hepatic veins.114

Pseudolesions and Pseudotumors

Pseudolesion and Pseudotumor Due to Third Inlow. Several

Various kinds of pseudolesions (focal masslike indings seen only on imaging) or pseudotumors (focal masslike parenchymal changes) are seen in the liver. As a irst step in the imaging diagnosis of focal hepatic mass lesions, exclusion of these entities is important. Pseudolesions and pseudotumors are often associated with localized intrahepatic portal low abnormalities.

kinds of direct venous inlow into the liver parenchyma from outside the main portal trunk have been analyzed by anatomic and imaging studies.27,99,183,185,274 These are called third inlow. The areas receiving third inlow are well demonstrated by CT during arterial portography (CTAP) as portal perfusion defects in an otherwise normal liver.99,183,274 According to CTAP-based analysis, third inlow includes low from an aberrant right gastric vein (or pancreaticoduodenogastric vein),183 cystic veins,185,340 veins of Sappey,137,229,259 and aberrant left gastric vein.294 These veins usually connect directly to the intrahepatic portal venules. The areas receiving third inlow often show pseudolesions or pseudotumors. To differentiate these entities from true hepatic mass lesions, visualization of these veins by color Doppler ultrasonography63,136 or dynamic CT is useful (Fig. 44-3). The cystic veins drain into the gallbladder fossa and communicate with the peripheral portion of the intrahepatic portal veins in segment IV or V.185,340 The drainage area often shows a tiny wedge-shaped area of early staining on dynamic CT and MRI because of earlier venous return relative to the surrounding liver (Fig. 44-4). On nonenhanced and postcontrast CT and MRI, no deinite abnormality is demonstrated. This staining can be better visualized when blood low is increased by gallbladder cancer or cystitis. This inlow through the cystic veins frequently causes focal sparing in a fatty liver.300 An aberrant right gastric vein accumulates blood from the gastric antrum, duodenum, and pancreas head; it is also referred to as the pancreaticoduodenogastric vein.37,183 The right gastric vein usually drains into the main portal trunk; however, it drains directly into the posterior aspect of segment IV of the liver in 6% to 14% of the general population and rarely into segment I, II, or III.182,183,274,335 The area drained by this vein occasionally demonstrates early enhancement on the arterial phase of dynamic CT and MRI (see Fig. 44-4) owing to relatively early venous return, focal sparing in a fatty liver (Fig. 44-5), focal fatty liver (Fig. 44-6), and hyperplastic change in a cirrhotic liver13,63,104,119,180,182,183,306 (Fig. 44-7). On MRI this change can be seen in around 5% of cirrhotic patients.306 For purposes of differentiation,

Arterioportal Shunt. In arterioportal (AP) shunt the hepatic arterial blood lows directly into the portal vein. AP communications are abundant through the peribiliary vascular plexus in the liver,41,42 and an AP shunt may form. However, as a result of biopsy or tumor, a direct istula between the artery and portal vein can be created. On dynamic CT and MRI, a wedge-shaped early enhancement is seen in the arterial phase, with occasional visualization of the portal venules in the center of the lesion; this area becomes isodense in the equilibrium phase (Fig. 44-1). Coronal or sagittal multidetector CT images are occasionally valuable for demonstrating these features. Because AP shunt is usually not visualized on superparamagnetic iron oxide (SPIO)-enhanced and hepatobiliary-phase gadoliniumethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)– enhanced MRI, these methods are effective in differentiating AP shunt from small hypervascular tumors or other true lesions.204,280 In hypervascular hepatocellular carcinoma (HCC), corona enhancement due to drainage low from the tumor is seen in the portal or equilibrium phase with washout from the tumor (discussed later).308 This hemodynamic pattern is different from that in AP shunt.307,343 The area with AP shunt often shows focal sparing in a fatty liver and rarely focal iron deposition.108 AP shunt is often associated with HCC, cavernous hemangioma, and other tumors.

Pseudolesion Due to Portal Vein Obstruction. Intrahepatic portal vein obstruction leads to various imaging indings in the obstructed segment that may result in its cause being obscured. Because of compensatory blood low from the hepatic artery to the distal

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FIG 44-1 Arterioportal shunt. On dynamic CT scan (B) a wedge-shaped early enhancement is seen in the arterial phase, with visualization of the portal venule in the center of the lesion (arrow). However, there are no visible abnormal indings on precontrast (A) and equilibrium-phase (C) CT images.

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FIG 44-2 Segmental staining caused by intrahepatic portal vein thrombosis. Although there are no attenuation differences in the liver on precontrast (A) and equilibrium-phase (C) CT scan, a wedge-shaped enhanced area is observed in segment VIII of the liver in the arterial phase (B) (arrow). A linear hypodense lesion that indicates a thrombus is observed in the portal vein (arrowhead).

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D FIG 44-3 Hypervascular pseudolesion in the posterior aspect of segment IV caused by an aberrant right gastric vein. A to C, Liver parenchyma of the posterior aspect of segment IV shows hyperdensity with a draining vein into this area on the portal phase of dynamic CT scan (arrow in B). This area is isodense on precontrast (A) and equilibrium-phase (C) images. D, Coronal maximum intensity projection during the portal phase indicates that the right gastric vein lows directly into this area and opaciies the parenchyma (arrow).

conirmation of the venous drainage by color Doppler is important.63 In addition, Gd-EOB-DTPA–enhanced MRI is also helpful for differentiation of these pseudolesions from HCC. On hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI, this hyperplastic area is not well visualized; on the other hand, the majority of early well-differentiated HCC shows hypointensity. Focal sparing of iron in hemosiderotic liver in this area was recently reported.116 The inferior veins of Sappey low into the anterior aspect of segment IV from the chest wall through the falciform ligament; they are also called paraumbilical veins. Focal fatty liver is often observed in this area136,137,259,338 (Fig. 44-8). This area also demonstrates early enhancement or hypodensity on dynamic CT and MRI.217 These changes are not seen in patients with portal hypertension because of reversed low in this venous system.

Miscellaneous Types of Pseudolesion. A hepatic segment with FIG 44-4 Hypervascular pseudolesion in the gallbladder fossa due to cholecystic venous drainage. Liver parenchyma around the gallbladder shows hyperdensity in the arterial phase of dynamic CT scan, owing to cystic venous drainage (arrows).

hepatic vein obstruction demonstrates the same imaging indings as a hepatic segment in an area with portal vein obstruction.114,207 This phenomenon is often observed in living donor liver transplantation.127 The drainage low from hypervascular HCC demonstrates corona enhancement surrounding the tumor, mimicking extratumoral

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FIG 44-5 Focal sparing in the posterior aspect of segment IV caused by aberrant right gastric venous drainage. A, On precontrast CT the liver parenchyma in the posterior aspect of segment IV shows relative hyperdensity compared with the background fatty liver parenchyma (arrow). On T1-weighted in-phase (B) and opposed-phase (C) MRIs, the liver parenchyma—except for the posterior aspect of segment IV (arrow in C)—has decreased intensity in the opposed-phase image, which indicates fat deposition.

extension of the malignant neoplasm on dynamic CT or MRI (peritumoral pseudolesion).308 There may be a spared area in a fatty liver (peritumoral spared area)55,98 and rarely peritumoral focal fatty change.194

Nontumorous Hepatic Mass Lesions Hepatic Cyst. Solitary liver cysts are occasionally encountered. His-

FIG 44-6 Focal fatty liver in the posterior aspect of segment IV caused by aberrant right gastric venous drainage. There is a relatively hyperattenuated round lesion (arrow) in the liver parenchyma in the posterior aspect of segment IV on in-phase T1-weighted MRI. The lesion shows hypointensity on opposed-phase T1-weighted MRI (image not shown).

tologically a single layer of cuboidal epithelium is seen and the wall is composed of thin ibrous tissue. These cysts are frequently noted in older adults, implicating acquired factors in their pathogenesis. Although hepatic cysts are generally asymptomatic, compressive symptoms may develop if they become massive. Similar cysts may form diffusely throughout the liver in adult-type polycystic liver. On CT a hepatic cyst is depicted as a smooth-rimmed hypodense mass with CT values near zero. They appear hypointense on T1-weighted images and extremely hyperintense on T2-weighted images. They show no enhancement at all on either postcontrast CT or MRI (Fig. 44-9). When hemorrhage or inlammation occurs in the center of these cysts, the CT value increases and the signal intensity on MRI undergoes a variety of changes. Such lesions are referred to as complicated cysts (see Fig. 44-9).

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FIG 44-7 Hyperplastic change in the posterior aspect of segment IV in an alcoholic cirrhotic liver caused by aberrant right gastric venous drainage. The liver parenchyma in the posterior aspect of segment IV shows hyperintensity (arrow) on T1- (A) and hypointensity (arrow) on the T2-weighted image (B). On the SPIOenhanced T2-weighted MRI (C) the area shows uptake of SPIO (arrow) and is relatively hypointense compared with the background liver parenchyma.

A

B FIG 44-8 Focal fatty change in the drainage area of the inferior veins of Sappey. On precontrast (A) and arterial-phase (B) CT scans, the anterior aspect of segment IV adjacent to the falciform ligament shows hypoattenuation (arrow), which represents focal fat deposition.

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B FIG 44-9 Hepatic cyst (polycystic liver). On T1-weighted (A) and T2-weighted (B) MRIs, there are multiple smooth-rimmed masses which demonstrate deinite homogeneous hypointensity and hyperintensity, respectively, similar to cerebrospinal luid. However, some of the cysts in the right lobe of the liver have a higher intensity than other cysts, which represents bleeding in the cyst (complicated cyst).

Polycystic Liver Disease. Polycystic liver disease can be seen in the pediatric population; when complicated by congenital hepatic ibrosis, it may be associated with portal hypertension and esophageal varices. Renal cysts are also present in approximately 70% of cases. Innumerable cysts are observed within the liver, with calciication and complicated cysts frequently noted. The imaging features of these cysts are basically the same as those of hepatic cysts (see Fig. 44-9).

Ciliated Hepatic Foregut Cyst. Ciliated hepatic foregut cyst (CHFC) is a unilobular and well-demarcated cyst whose inner surface is ciliated and covered with mucin-producing cylindrical or cubic epithelium. Histologically they are the same as bronchogenic cysts.53,109,292 These cysts tend to occur on the anterior surface of the liver beneath the hepatic capsule. They contain mucinous luid with various concentrations of proteins and fats. Although CHFC is typically benign, malignant transformation to squamous cell carcinoma has been reported in few cases.53 The imaging indings of CHFC differ according to the concentration of mucin and the nature of the cyst’s contents.53,109 On nonenhanced CT, CHFC is often depicted as an isodense nodule relative to the surrounding liver; it is sometimes hyperdense or slightly hypodense. On dynamic CT the cyst does not enhance at all. On T2-weighted MRI, the indings are the same as those of hepatic cysts. On T1-weighted MRI, hyperintensity due to the presence of high concentrations of mucin is noted in some cases (Fig. 44-10).

Masslike Focal Parenchymal Changes Focal sparing in fatty liver. Focal sparing in fatty liver shows relative hyperdensity on nonenhanced CT (see Fig. 33-5), hypointensity on T1-weighted images, and relative hyperintensity on opposed-phase T1-weighted images (see Fig. 44-5). This inding is usually related to disturbances of localized portal low, and its coniguration is occasionally wedge shaped.13,180 Focal fatty change. Focal fatty liver is also strongly related to localized portal low disturbances.119 Common locations and imaging features are as described earlier under the heading “Pseudolesion Due to Portal Vein Obstruction” (see Figs. 44-6 and 44-8). Focal fatty liver can mimic dysplastic nodules or well-differentiated HCC with fatty change in cirrhotic livers (see “Hepatocellular Carcinoma,” later), and

the differentiation is often dificult when the change occurs in uncommon locations. Multiple focal nodular fatty iniltrations are rarely encountered and can mimic metastatic liver cancer, microabscesses, and biliary hamartomatosis (Fig. 44-11). Opposed-phase MRI can identify the fatty change and is useful in differentiating among these entities (see Fig. 44-6).148 Focal iron deposition. Focal iron deposition can be seen in areas with disturbed portal perfusion and results in segmental hypointensity on T2-weighted images.108 Focal nodular hyperplasia. Focal nodular hyperplasia (FNH) is deined as a tumorlike lesion characterized by a central ibrous scar with surrounding nodules of hyperplastic hepatocytes and small bile ductules in noncirrhotic livers. Most cases occur in women (the maleto-female ratio is 1 : 8).87 Because it is often associated with intrahepatic portal low disturbance, FNH is now considered a reactive change to abnormal blood circulation.143 Unlike hepatic adenoma, the association with oral contraceptive use is still controversial.67 Clinically FNH is usually asymptomatic, with epigastric pain or hepatomegaly infrequently developing. Unlike in hepatic adenoma, intraperitoneal rupture is extremely rare. Grossly FNH is a well-demarcated solitary mass without a capsule, often located beneath the surface of the liver. However, it can be multiple and pedunculated from the liver. Internal bleeding and necrosis are not usually seen. In the central scar, feeding arteries, draining veins connected to the hepatic vein, and bile duct proliferation are seen.56 The feeding arteries distribute to the peripheral portion of the tumor through the central scar in a spoke-wheel pattern. Variable amounts of Kupffer cells are present in FNH. On imaging, FNH usually has a slightly elliptical shape. On nonenhanced CT it appears as a homogeneous hypodense mass with a central scar showing more marked hypodensity. However, in small lesions, visualization of the central scar is not deinite on CT. The entire nodule is well and homogenously enhanced in the arterial phase of CT and MRI. The central scar is seen as more hypodense,267 but in small lesions it is depicted infrequently.31 If vessels radiating from the central scar to the periphery of the tumor are visualized, a near-deinitive diagnosis of FNH can be made. In this spoke-wheel pattern, the feeding vessels penetrate the ibrous septum from the central scar and distribute to the tumor (Figs. 44-12 and 44-13). This vasculature is most sensitively delineated by contrast-enhanced ultrasonography.

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C FIG 44-10 Ciliated hepatic foregut cyst. A, Postcontrast CT scan shows a nonenhanced hypodense mass beneath the anterior surface of the liver (arrow). The internal density of the mass is higher than that of water. Both T1- (B) and T2-weighted (C) MRIs demonstrate extreme hyperintensity, relecting a high intralesional concentration of protein (arrow).

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hypervascular lesions show early enhancement in the arterial phase of dynamic CT and MRI, with variable signal intensity on T1- and T2-weighted images. On Gd-EOB-DTPA and SPIO-enhanced MRI, uptake of these contrast mediums can be seen. Recently this kind of lesion has attracted particular attention in patients with alcoholic liver cirrhosis. Furthermore, recent immunohistochemical analysis revealed that around two thirds of these nodules associated with alcoholic cirrhosis could be categorized into inlammatory-type hepatic adenoma (named serum amyloid A [SAA]-positive neoplasm because the existence of hepatic adenoma in cirrhotic livers are not well accepted), different from the other one third demonstrating the immunohistochemical features of FNH. Interestingly the former shows hypointensity but the latter iso- or hyperintensity on hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI.260

Macroregenerative Nodules. Macroregenerative nodules are inciFIG 44-11 Multiple nodular fatty deposition in type C cirrhotic liver. On precontrast CT, multiple small hypodense nodules are observed in the liver. Multiple nodular fatty depositions were conirmed by MRI and follow-up studies.

FNH in most cases shows hypointensity on T1- and hyperintensity on T2-weighted images. However, because the tissue composition of FNH resembles that of the surrounding liver, it can exhibit isointensity on T1- or T2-weighted images. The central scar is depicted as hypointense on T1- and hyperintense on T2-weighted images (see Fig. 44-12). The inding of hyperintensity on the latter is attributable to the presence of a rich vasculature within the scar tissue (vascular scar).154 On dynamic MRI, homogeneous early enhancement is seen, with persistent staining. The central scar shows delayed enhancement.170 Both imaging and pathology studies have clariied that in FNH, the majority of the blood low supplying the tumor from arteries reluxes to veins within the central scar and then enters the hepatic vein.56,193 The hemodynamics of FNH differs from that of hypervascular HCC (described later under “Hepatocellular Carcinoma”), and this difference is useful in the differential diagnosis. On dynamic CT and MRI of FNH, the margin of the stain is clear; hence washout of the contrast agent is not observed (see Figs. 44-12 and 44-13).193 In addition, direct draining from the tumor to the hepatic vein is occasionally depicted (see Fig. 44-12). Because Kupffer cells are present in FNH, the signal intensity decreases on SPIO-enhanced MRI (see Fig. 44-12). The degree of uptake is variable depending on differences in the distribution density of Kupffer cells.70,236 Hepatobiliary agents such as mangafodipir trisodium (Mn-DPDP) and Gd-EOB-DTPA are useful in the characterization of FNH. Because the hepatocytes in FNH take up these agents, FNH shows hyperintensity on T1-weighted images enhanced by them319,345 (Fig. 44-14). FNH often shows donut or ring-like peripheral hyperintensity on hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI (Fig. 44-15) because of lower expression of organic anion transporting polypeptide (OATP)1B3, which uptakes Gd-EOB-DTPA into hepatocytes in the hyperplastic hepatocyte surrounding the central scar.54,195,332 Recently, telangiectatic FNH, which was formerly categorized as one of the subtypes of FNH, was categorized into the subtypes of hepatic adenoma (inlammatory adenoma).22 FNH-like lesions. FNH-like nodules are focal lesions occurring in cirrhotic livers that are morphologically similar to classic FNH in otherwise normal livers.160,216,245,268,289 They are sometimes misdiagnosed as HCC on imaging because both lesions show deinite enhancement in the arterial phase of dynamic CT or MRI.245 These

dentally detected in patients with cirrhosis and Budd-Chiari syndrome.26,168,317 They are larger than the usual regenerative nodules in some cases. Histologically, macroregenerative nodules resemble the regenerative nodules seen in cirrhosis. They typically exhibit hypointensity on T2-weighted images and various signal intensities on T1-weighted images. On dynamic CT and MRI they generally do not enhance, although in Budd-Chiari syndrome they may be multiple and show enhancement (Fig. 44-16).

Nodular Regenerative Hyperplasia. Nodular regenerative hyperplasia consists of multiple monoacinar regenerative nodules in the absence of ibrous septa, with increased intranodular portal supply. It is frequently associated with various nonhepatic chronic diseases, including myeloproliferative disorders (leukemia, polycythemia vera), lymphoproliferative disorders (lymphoma, plasma cell dyscrasia), and collagen diseases (rheumatoid arthritis, polyarteritis nodosa, lupus erythematosus). The pathogenesis of nodular regenerative hyperplasia remains unclear, but it may be similar to that of partial nodular transformation; the differences between these two entities are related to the cause and the distribution of the portal vein obliteration.320 Imaging features of these nodules include hypointensity on T2weighted images; in contrast, true hepatic tumors usually show hyperintensity on T2-weighted images. On T1-weighted images they typically demonstrate hyperintensity.270 These MRI indings are similar to those of the hyperplastic changes caused by aberrant venous drainage in cirrhotic livers and by dysplastic nodules or well-differentiated HCC. Gd-EOB-DTPA may show donut-type hyperintensity similar to FNH on hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI (Fig. 44-17).

Peliosis Hepatis. Peliosis hepatis consists of multiple small cystic lesions that communicate with sinusoids. Peliosis hepatis does not have endothelial cells in the cystic wall.321 On nonenhanced CT, peliosis hepatis is hypodense. It shows enhancement relative to the background liver in the arterial phase of dynamic CT and becomes progressively isodense. Peliosis hepatis usually demonstrates hyperintensity on T2-weighted MRIs; on T1-weighted images it is hypointense compared with the background liver. On T1-weighted images after contrast enhancement, peliosis hepatis may exhibit a centrifugal enhancement pattern.88

Biloma. Biloma refers to a localized collection of bile that has escaped from the biliary tract, regardless of whether its location is intrahepatic or extrahepatic. Because the bile duct may rupture for a variety of reasons, including choledochal stones, bilomas may also form within the liver and subcapsular area.49,199 There has been a recent increase in the incidence of bilomas associated with bile duct injury

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FIG 44-12 Focal nodular hyperplasia in a 44-year-old woman. A to C, On precontrast CT scan there is a homogeneous slightly hypodense mass with a central scar (slightly more hypodense) in the lateral segment of the liver (arrow in A). B, The lesion shows homogeneous enhancement with a less-enhanced central scar in the arterial phase (arrow). C, It is relatively hypodense compared with surrounding liver parenchyma, with a slightly enhanced central scar in the equilibrium phase (arrow). D, Direct draining from the tumor to the left hepatic vein (arrow) is observed on a coronal reconstruction of arterial-phase CT. The tumor shows isointensity (arrow) on T1- (E) and T2-weighted (F) MRIs. It demonstrates isointensity to the surrounding background liver parenchyma (arrow) on a SPIO-enhanced T2-weighted MRI (G), which represents the tumor’s uptake of SPIO.

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FIG 44-13 Focal nodular hyperplasia in a 15-year-old girl. The arterial phase of dynamic CT shows an enhanced tumor (arrows) and the feeding arteries radiating from the central scar to the periphery (spokewheel pattern).

FIG 44-14 Retention of hepatobiliary contrast agent in a 34-year-old man with focal nodular hyperplasia. In the delayed-phase (hepatobiliaryphase) T1-weighted image obtained 20 minutes after administration of Gd-EOB-DTPA, the tumor shows prolonged enhancement (arrow) that represents uptake of the contrast agent by hepatocytes.

FIG 44-16 Hypervascular macroregenerative nodule in Budd-Chiari syndrome in a 28-year-old man. The nodule shows hyperdensity in the arterial phase of dynamic CT. The nodule demonstrated hyperintensity on T1- and isointensity on T2-weighted MRIs (not shown).

FIG 44-15 Donut or ringlike peripheral retention of hepatobiliary contrast agent in focal nodular hyperplasia. In the delayed-phase (hepatobiliary-phase) T1-weighted image obtained 20 minutes after administration of Gd-EOB-DTPA, the central scar portion shows lower expression of organic anion transporter polypeptide, and the tumor shows donut or ringlike peripheral retention of contrast agent.

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FIG 44-17 Nodular regenerative hyperplasia in idiopathic portal hypertension. A, On T1-weighted MRI, there is a hyperintense nodule with a central hypointense portion. B, On T2-weighted MRI, the nodule appears hypointense with a central hyperintense portion. C, On hepatobiliary-phase Gd-ROB-DTPA–enhanced MRI, the nodule shows hyperintensity that relects uptake of EOB. D, On CTAP, the nodule appears hyperdense compared to the background liver, which suggests increase of portal low compared to the surrounding liver.

after interventions such as transcatheter arterial embolization and radiofrequency ablation, as well as hepatic artery thrombosis following liver transplantation.129,138,261 The imaging indings of biloma resemble those of hepatic cyst, with proximal bile duct dilatation frequently noted. If hepatobiliary scintigraphy reveals accumulation, a deinitive diagnosis can be made. Hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI may also help diagnose the presence of biloma.152

Biliary Hamartoma. Biliary hamartoma, also known as von Meyenburg’s complex, is thought to be the result of a congenital defect in formation of the ductal plate. It is occasionally complicated by polycystic disease or peribiliary cysts.243 Biliary hamartoma is composed of bile ductule–like clusters surrounded by ibrous interstitium; it is not necessarily a rare condition, having been noted in 0.15% to 2.8% of cases in autopsy series. These nodules are usually small, in the range of 0.1 to 5 mm, but can occasionally measure up to 10 mm. In some cases they are limited to only one part of the liver; in other cases they are interspersed throughout. On nonenhanced CT, biliary hamartoma is depicted as tiny hypodense nodules; they do not show water attenuation because of a partial volume effect. These nodules may be dificult to differentiate

from hypovascular solid masses, particularly metastatic liver cancer, multiple microabscesses, and irregular fatty iniltration. On T2weighted MRIs and MR cholangiopancreatography (MRCP), they characteristically show marked hyperintensity, relecting their cystic nature156,198,263 (Fig. 44-18).

Peribiliary Cysts. Peribiliary cysts are considered to be retention cysts of the peribiliary glands. They are frequently associated with polycystic liver and cirrhosis.213,291 In liver cirrhosis they gradually increase in size and number with disease progression. On ultrasonography they are depicted as round or tubular anechoic lesions situated along the larger portal tracts.290 On CT and MRI they are depicted as tubular lesions along the portal vein or as beaded communicating cystic lesions.19,85,97,293 However, in some cases, the indings resemble a periportal collar on CT and periportal abnormal signal intensity on MRI.181 Characteristically, lesions are present on both sides of the proximal intrahepatic portal vein. Peribiliary cysts can exhibit the “central dot” sign on enhanced CT, like that seen in Caroli’s disease.1 MRCP is useful for obtaining the total picture of peribiliary cysts (Fig. 44-19). On endoscopic retrograde cholangiopancreatography (ERCP), contrast medium does not low into peribiliary cysts, which is useful in differentiating them from Caroli’s disease.202

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B FIG 44-18 Multiple biliary hamartomatosis (von Meyenburg’s complex). A, On postcontrast CT, there are multiple minute hypodense nodules throughout the liver. B, On T2-weighted MRI at the same level, the nodules exhibit extreme hyperintensity. Most of the nodules are dificult to recognize on CT because of the partial volume effect.

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FIG 44-19 Peribiliary cysts. A, Tubular hypointense lesions are apparent along the large portal vein, especially in the hepatic hilum area (arrow), on T1-weighted MRI. B, On T2-weighted MRI these lesions show hyperintensity (arrow). Actually, these lesions are not tubular but represent multiple small cysts around the large bile duct. C, On MRCP, multiple hyperintense cystic lesions are observed around large bile ducts in the hepatic hilum area (arrow).

Caroli’s Disease. Caroli’s disease is a rare condition causing cystic dilation of the intrahepatic bile duct. It is somewhat more frequent in males and is detected in childhood or adolescence in most cases because of symptoms resulting from cholangitis or hepatic abscess. In the majority of cases, renal cystic disease, including renal tubular ectasia, is associated.214 On ultrasonography and CT, cystic dilatation of the bile duct is characteristic.157,190,199 The portal vein within a dilated bile duct is well visualized as a punctate or linear stain on enhanced CT, known as the central dot sign35 (Fig. 44-20). This portal vein also shows a low void on MRI, called an intracystic central low void sign.73

Infectious Liver Masses Pyogenic abscess. Bacteria can reach the liver via the portal vein, hepatic artery, or bile duct, as well as by direct infection from adjacent structures.86 Many cases of pyogenic abscess are associated with ascending cholangitis due to bile duct disease; however, the cause is often

unclear, and in such cases the route of infection is presumed to be via the portal vein. Escherichia coli and Klebsiella species are the most common causative bacteria. Imaging indings reveal a variety of stages and degrees of severity, but basically an abscess cavity with a center illed with pus and inlammatory changes in the adjacent tissues are noted. Lesions are both unilocular and multilocular as well as multiple and solitary. Cases associated with cholangitis tend to be multiple. Cases due to bacteremia frequently show multiple microabscesses. The shape of the abscess cavity is generally irregular, while its margin tends to assume a clear, round shape in the healing stage. On nonenhanced CT, marked hypointensity due to the presence of pus in the center of the abscess is found. In addition, slight hypointensity, presumably due to the inluence of inlammation on the adjacent tissues, produces a characteristic double-structured hypodense area.74 Although the shape is usually irregular, in a few cases it is virtually round, and the double structure is not clearly seen. Fusion of small

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B FIG 44-20 Caroli’s disease. A, Precontrast CT scan shows multiple cystic lesions that contain dotlike structures. Some of these cystic lesions contain calciied stone (arrow). B, On postcontrast CT scan the dotlike structures are well enhanced and recognizable as portal veins.

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FIG 44-21 Hepatic abscess caused by intrahepatic cholelithiasis. A, On precontrast CT scan there is a hypodense mass (arrow). B, On arterial-phase CT the mass has a target-like appearance (arrow)—a hypodense center surrounded by an enhanced hyperdense middle and a hypodense periphery. Transient wedge-shaped segmental enhancement is also observed surrounding the mass (arrowhead). C, On equilibrium-phase CT the middle and outer parts of the mass show a thick ringlike enhancement (arrow).

abscesses to form a large abscess is sometimes observed (cluster sign).106 During the arterial phase of dynamic CT, a double-target sign175 is seen: the area around the center, which is not enhanced, is stained (medial layer); the outermost layer shows hypodensity. In the portal to equilibrium phases, a thick ringlike stain due to staining of the medial and outermost layers is seen. Also, during the arterial phase, segmental or wedge-shaped enhancement is transiently found around the abscess (Fig. 44-21). This wedge-shaped enhancement disappears in the late phase. It may be attributed to narrowing or obstruction of the portal vein branches due to inlammatory changes of the portal tract around the abscess, which results in decreased portal low and a compensatory increase in arterial low.62 On MRI, liver abscesses show hyperintensity on T2-weighted images, with the abscess cavity showing even more marked hyperintensity.17,120,188 During the arterial phase of dynamic MRI, as on dynamic CT, transient wedge-shaped enhancement is shown around the abscess; in the same area on T2-weighted images, wedge-shaped hyperintensity

may be shown (Fig. 44-22). Because these indings are changeable after 1 to 2 weeks of antibiotic therapy, this helps differentiate abscesses from malignant tumors.62 Gas bubbles can be rarely found. Bile duct diseases are the most common cause of liver abscess. In particular, abscess frequently evolves from cholangitis, making early diagnosis of cholangitis of great importance. Clinically, cholangitis should be suspected in the presence of fever and elevated ductal enzymes. In the arterial phase of dynamic CT, acute cholangitis characteristically shows transient diffuse enhancement along the portal tracts within the liver12 (Fig. 44-23). Amebic abscess. Amebic abscess, which results from Entamoeba histolytica infection, is a frequent type of hepatic abscess in tropical and subtropical regions. Because it is generally secondary to amebic infection of the colon, it reaches the liver via the portal vein.47 As the abscess progresses, its core undergoes liquefaction and cavitary changes and becomes surrounded by necrotic inlammatory cell iniltration and ibrous layers. In the liver, one large focus is usually found, although

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FIG 44-22 Hepatic abscess of unknown cause. A, On fat-suppressed T2-weighted MRI there is an inhomogeneous hyperintense mass (arrow) with a very hyperintense area, suggesting a collection of pus. B, On arterial-phase Gd-enhanced T1-weighted MRI the peripheral part of the mass shows wedge-shaped segmental enhancement (arrowhead). Septum-like enhancement in the mass is also observed (arrow). C, On the equilibrium-phase image a nonenhanced cystic mass with an enhanced irregular thick wall is visualized (arrow).

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B FIG 44-23 Intrahepatic cholangitis with choledocholithiasis. A, In the portal phase of dynamic CT, there is transient diffuse enhancement along the portal tract within the liver; this disappears during the equilibrium phase (B).

multiple foci are sometimes seen. In a few cases the abscess ruptures, leading to abscess formation in the lung or peritoneal cavity.107,227 The imaging indings are essentially nonspeciic and resemble those of pyogenic abscess.200,248,249 Postcontrast CT reveals an enhanced mural structure with a strong tendency to exhibit a hypodense area at its lateral side owing to the presence of edema. Segmental enhancement similar to that seen with bacterial abscess is noted in some cases.

Fungal abscess. Fungal abscess is caused by an opportunistic infection seen in immunosuppressed patients such as those with acquired immunodeiciency syndrome (AIDS) or leukemia or those who have undergone bone marrow transplantation or treatment for malignant tumors.5,238 Candidiasis is the most common fungal infection encountered. In most cases it presents as multiple microabscesses. In many cases lesions develop in the spleen and liver simultaneously.

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B FIG 44-24 Hepatic and splenic microabscesses (Candida) in a patient with acute myelogenous leukemia. A, In the arterial phase of dynamic CT there are multiple small nodules with faint peripheral ringlike enhancement in the liver and spleen (arrows). B, On equilibrium-phase CT they appear hypodense compared with the background liver (arrows).

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B FIG 44-25 Hepatic microabscesses in a patient with acute lymphocytic leukemia. A, On arterial-phase Gd-enhanced T1-weighted MRI there are small hypointense nodules with faint peripheral ringlike enhancement (arrows). B, On fat-suppressed T2-weighted MRI these lesions appear hyperintense and additional smaller nodules are observed (arrows).

Microabscess shows faint ringlike enhancement in the arterial phase of dynamic CT and hypodensity in the equilibrium phase (Fig. 44-24). Calciications are sometimes present in chronic microabscesses. On T1-weighted images they demonstrate hypointensity, and on T2-weighted images, marked hyperintensity. On dynamic MRI, as on CT, the rim of the lesion is preferentially enhanced8 (Fig. 44-25). Actinomycosis, an infection caused by Actinomyces israelii, usually assumes a chronic course.279 Most commonly, liver lesions develop via the portal vein from foci located in the intestines, particularly the ileocecal area. Occasionally pulmonary lesions penetrate the diaphragm and spread to the liver. Liver lesions characteristically form a honeycomb abscess that contains 1- to 2-mm fungus balls. The

imaging indings resemble those of granuloma (described later under “Granuloma”), with slightly to moderately increased vascularity. In the arterial phase of dynamic CT, a solid mass that is isodense or hyperdense relative to the surrounding liver is noted. In the equilibrium phase, delayed enhancement is seen.326

Inlammatory Pseudotumor. Inlammatory pseudotumor, which is also called plasma cell granuloma and postinlammatory tumor, is characterized histologically by connective tissue proliferation associated with plasma cell and ibroblast iniltration.262 Similar lesions are commonly found in the lungs, ocular fossa, and parotid glands; they are rare in the liver,220 although the number of reported cases has recently

CHAPTER 44 increased. The pathogenesis of inlammatory pseudotumor is divided into two types. In the irst, inlammation (e.g., liver abscess) is surmised to be the cause (ibrohistiocytic type); in the other, autoimmune mechanisms are implicated (lymphoplasmacytic type).222,347 Hepatic inlammatory pseudotumor may be associated with other unusual inlammatory or autoimmune diseases such as sclerosing cholangitis, phlebitis, and retroperitoneal ibrosis.347 Inlammatory pseudotumor infrequently involves the porta hepatis or bile duct, which results in obstructive jaundice.347 Spontaneous regression has been reported.328 The imaging indings of pseudotumors caused by inlammation are the same as those of fresh granuloma, with the imaging indings differing according to the degree of ibrous change and inlammatory cell iniltration in the mass. When inlammatory cell iniltration is predominant, enhancement is seen in the arterial phase; when ibrous tissue predominates, delayed enhancement is seen on postcontrast CT, as in tumors with a rich ibrous interstitium58,333 (Fig. 44-26).

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Autoimmune pseudotumor is associated with autoimmune pancreatitis in a high proportion of cases, either synchronously or nonsynchronously, and it is considered to be one type of immunoglobulin (Ig)G4-related autoimmune disease.222,347 In this condition an inlammatory mass forms at a periductal site, resulting in dilation of peripheral bile ducts owing to intrahepatic bile duct stricture in some cases (Fig. 44-27). The imaging indings resemble those of hepatic hilar cholangiocarcinoma.

Granuloma. Hepatic granuloma is associated with a wide range of underlying factors, including bacterial, viral, parasitic, and fungal infections; biliary tract diseases; systemic diseases such as sarcoidosis; and exposure to various pharmacologic and chemical substances.18,123,235,315 With the exception of cases associated with infection, most lesions are microscopic and thus not a suitable focus for diagnostic imaging. Among infection-related lesions, bacterial hepatic abscess frequently assumes a chronic course, as do some cases of

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E FIG 44-26 Inlammatory pseudotumor. A to C, On precontrast CT a large isodense mass with a peripheral hypodense rim is observed (arrow in A). In the arterial phase the mass shows faint enhancement with a less-enhanced outer rimlike structure (arrow in B). In the equilibrium phase the central part demonstrates slight enhancement and the peripheral part demonstrates dense delayed enhancement (arrow in C). D, On T1-weighted MRI the central part of the mass shows isointensity and the peripheral part, hypointensity (arrow). E, On T2-weighted MRI it is visualized as an area of inhomogeneous hyperintensity (arrow).

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PART II CT and MR Imaging of the Whole Body fungal and parasitic infection. Also, caseous necrosis develops in the core of some tuberculomas.118 Calciication is frequent in infectious granulomas.3,278 The imaging indings of granuloma differ according to stage. Granulomas with marked inlammatory cell iniltration show slight to moderate vascular proliferation and are enhanced in the arterial phase of dynamic CT and MRI. In the late phase they show isointensity or moderate hyperintensity relative to the surrounding liver, with this inding characteristically persisting long term. When an old ibrous component makes up the bulk of the lesion, it becomes hypovascular, and although it is not clearly enhanced on dynamic CT, it shows delayed enhancement relative to the surrounding liver on late-phase CT.65,337 On MRI it shows hypointensity and hyperintensity on T1- and T2-weighted images, respectively (Fig. 44-28), making it dificult to distinguish from tumor. Some lesions with prominent ibrosis exhibit hypointensity on T2-weighted images. These indings are similar to those of highly ibrous cholangiocarcinomas, cholangiolocellular carcinoma, and liver metastases of scirrhous cancer, making the differential diagnosis extremely dificult.

FIG 44-27 Autoimmune-related inlammatory pseudotumor. On postcontrast CT a slightly hypodense mass is observed along the left portal vein (arrow). This is an IgG4-related inlammatory mass in the area of the bile ducts.

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E FIG 44-28 Hepatic granuloma (unknown cause) in a 39-year-old woman. A to C, On precontrast CT a hypodense nodule is observed (arrow in A). B, In the arterial phase it shows faint enhancement (arrow). C, In the equilibrium phase it demonstrates delayed enhancement and becomes isodense to the background liver (arrow). On T1- (D) and T2-weighted (E) MRIs, the nodule appears hypointense and hyperintense, respectively (arrow).

CHAPTER 44 Eosinophilic Abscess. Hepatic eosinophilic abscess is commonly associated with peripheral eosinophilia. Activated Kupffer cells stimulate the eosinophils to release some humoral factors that induce localized coagulopathy and thromboembolism. Histopathologically, eosinophilic abscess consists of coagulation necrosis and inlammatory cell iniltration, especially eosinophils. Eosinophilic abscess shows hypodensity on postcontrast CT, with indistinct margins and nonspherical contours344 (Fig. 44-29).

Parasitic Diseases. The following parasitic diseases might show mass lesion on imaging: Echinococcus granulosus (hydatid) cyst,112,200 Echinococcus multilocularis,139,200 schistosomiasis (Schistosoma japonicum, Schistosoma haematobium, and Schistosoma mansoni),196,197,200 fascioliasis,76 clonorchiasis,33,161 and visceral larva migrans.32

Vascular Diseases Hepatic infarction. The normal liver receives approximately 60% to 65% of its blood low via the portal vein and 35% to 40% via the hepatic artery, making it less susceptible to infarction than most other organs. Most hepatic infarctions are due to hepatic artery occlusion

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associated with systemic circulatory disturbance.228,303 Histologically, coagulation necrosis is found in the infarct center, with compensatory hyperemia seen in the periphery. An ill-deined wedge-shaped hypodense area is seen on CT. When bleeding is present, the center may appear hyperdense. On enhanced CT or MRI, the infarcted area does not stain. In acute hepatic necrosis, gas may be noted in the necrotic focus7,271 (Fig. 44-30). When portal low is reduced for whatever reason, the number of hepatocytes decreases and the hepatic sinusoids undergo dilation and hyperemia. This is known as Zahn’s infarction. This entity is widely seen in cases of intrahepatic portal vein obstruction due to thrombosis and tumor growth (Fig. 44-31). Anoxic pseudolobular necrosis. Anoxic pseudolobular necrosis (focal ischemic necrosis) is coagulative necrosis that involves one or more pseudolobules in cirrhotic livers. It usually follows massive gastrointestinal hemorrhage and shock. It is occasionally dificult to differentiate from HCC with massive internal coagulation necrosis.55,125,147 When ischemic necrosis of regenerative nodules is seen diffusely, it is called ischemic hepatitis. This mimics diffuse hypovascular HCC or metastasis111 (Fig. 44-32).

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FIG 44-29 Eosinophilic abscesses in a 79-year-old man. On precontrast CT (A), multiple slightly hypodense masses of various sizes and shapes are seen. They are not enhanced on arterial-phase (B) and equilibriumphase (C) images.

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B FIG 44-30 Hepatic infarction. A, Precontrast CT scan shows wedge-shaped hypodense areas in the peripheral portion of the liver (arrows). B, They demonstrate no enhancement on equilibrium-phase CT scan (arrows).

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B FIG 44-31 Zahn’s infarction. A, On precontrast CT the left and caudate lobes of the liver show slight hypodensity (arrows). B, In the arterial phase of dynamic CT these lobes demonstrate segmental staining (arrows).

FIG 44-32 Ischemic necrosis of regenerative nodules following esophageal variceal rupture in a cirrhotic patient. Postcontrast CT scan shows tiny nonenhanced nodules with an irregular and patchy coniguration (arrows).

Conluent hepatic ibrosis. Conluent hepatic ibrosis is observed in about 14% of patients with advanced cirrhosis who undergo liver transplantation. Histopathologically, approximation of remnant portal triads within the ibrotic areas are seen. On nonenhanced CT, conluent hepatic ibrosis shows wedge-shaped or geographic hypodensity. After contrast enhancement, the lesion becomes less obvious compared with nonenhanced CT.230 On MRI the lesions are hyperintense on T2-weighted images and hypointense on T1-weighted images compared with the background liver231 (Fig. 44-33).

Benign Hepatic Tumors Cavernous Hemangioma. Cavernous hemangioma is the most frequently encountered benign hepatic tumor in clinical practice, with an

incidence between 0.4% and 20%.241,265 It is seen in all age groups and has a female preponderance. It is detected in the absence of signs and symptoms in almost all cases. When the tumor exceeds 4 cm, abdominal pain or discomfort or a palpable mass may be present. Rupture occurs rarely.240,241 Rare complications of giant lesions include consumptive coagulopathy, thrombocytopenia, and hypoibrinogenemia (Kasabach-Merritt syndrome).6 Hemangiomas are usually solitary but are multiple in approximately 10% of cases. Their borders are clear, but they are not encapsulated. The cut surface is spongelike and typically dark reddish. Histologically it is made up of variously sized vascular spaces lined by lat endothelial cells and interspersed with ibrous tissue. As the hemangioma grows, various degenerative changes are seen in its center, including old and new thrombus formation, necrosis, scarring, hemorrhage, and calciication.316 When degeneration and ibrous changes become more prominent, the lesion is referred to as a sclerosed hemangioma.2,174 On nonenhanced CT, hemangioma is depicted as a well-demarcated hypodense area with the same density as the aorta. It is sometimes round but more often oval or irregular. Large lesions sometimes have a geographic (irregular) shape. In the arterial phase of dynamic CT, peripheral enhancement is seen irst, followed by gradual illing toward the center (illing in) and prolonged enhancement on the equilibrium phase—a pattern characteristic of hemangioma. The density of hemangiomas relects the vascular spaces, and on precontrast, arterial, and equilibrium-phase dynamic CT, the fact that the tumor’s density is similar to that of the aorta is useful diagnostic proof101,155,246 (Fig. 44-34). In the type of small hemangioma containing small sinusoids, dynamic CT may show the entire tumor to be enhanced from the early phase316 (Fig. 44-35). In hemangiomas exceeding 4 cm, a more irregular hypodense area in the center or a septum-like structure may be found because of thrombus, necrosis, and scar formation (Fig. 44-36). Calciication and cystic degeneration are also found in some cases.83,192 Rarely, luid-luid formation is seen.102 T1-weighted MRIs show homogeneous hypointensity, and T2-weighted images show homogeneous marked hyperintensity. The signal intensity on T2 is usually higher than that of the spleen (see Figs. 44-34 to 44-36).305 On dynamic MRI the enhancement pattern is the

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FIG 44-33 Conluent hepatic ibrosis in hepatitis C–related cirrhotic liver. A, Precontrast CT shows a geographically hypodense area (arrow). B, The lesion demonstrates delayed enhancement on postcontrast CT (arrow). The lesion shows hypointensity (arrow) on T1- (C) and hyperintensity (arrow) on T2-weighted MRI (D).

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FIG 44-34 Cavernous hemangioma and HCC in a patient with hepatitis C–related chronic hepatitis. A to C, On precontrast CT a hypodense mass is observed (arrow in A). B, In the arterial phase it shows peripheral dense, spotty enhancement (arrow). C, In the equilibrium phase the attenuated area spreads throughout the mass; this is called filling in (arrow). The density of the lesion is almost the same as that of the aorta in all phases of dynamic CT. D, On T2-weighted MRI the mass demonstrates deinite hyperintensity (arrow) similar to spinal luid. It shows slight peripheral enhancement (arrow) on the arterial-phase Gd-enhanced T1-weighted image (E) and illing in (arrow) on the late-phase image (F). Arrowheads in B, D, and E indicate associated minute HCC.

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FIG 44-35 Small hepatic hemangioma—early enhancing type. A, T1-weighted MRI shows a small hypointense mass (arrow). B, The mass demonstrates extreme hyperintensity (arrow) on the T2-weighted image. C, Arterial-phase Gd-enhanced T1-weighted MRI reveals deinite enhancement of the entire tumor (arrow). D, Prolonged enhancement is shown in the late phase (arrow).

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FIG 44-36 Giant cavernous hemangioma with central liquefaction. A, On the T1-weighted image the mass shows deinite hypointensity, with even more hypointense central portions (arrow). B, On the T2-weighted image, the mass demonstrates deinite hyperintensity, and the portions that appear very hypointense on T1 show more hyperintensity (arrow). C, The equilibrium-phase Gd-enhanced MRI reveals illing in and prolonged enhancement with central nonenhanced portions, indicating central liquefaction (arrow).

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FIG 44-37 Sclerosed hemangioma. Postcontrast CT shows a slightly enhanced mass with internal heterogeneity (arrow).

same as that seen on CT. The larger the lesion becomes, the more inhomogeneous it appears on diagnostic imaging because of thrombus and scar formation in the center (see Fig. 44-36). Small AP shunts can complicate even small hemangiomas and are not rare. A hemangioma with an AP shunt usually shows enhancement of the entire lesion from the early phase, with less marked enhancement seen in the late phase compared with the early one.128 Sclerosed hemangiomas show hypodensity with delayed enhancement on dynamic CT and hypointensity in relation to cerebrospinal luid on T2-weighted images2 (Fig. 44-37). Hemangioma occasionally appears as a so-called pseudo-washout sign in the transitional (late) phase of dynamic Gd-EOB-DTPA MRI and might mimic hypervascular HCC.43

Hepatic Adenoma. Hepatic adenoma tends to occur in a younger group compared with FNH and overwhelmingly affects women, most of whom have a history of oral contraceptive use. In addition the relationship between this tumor and glycogen storage disease is well recognized.122 In many cases hepatic adenoma is discovered because of an abdominal mass or recurrent abdominal pain, but it can also present as acute abdomen owing to tumor rupture. Hepatic adenoma develops in noncirrhotic livers and is usually solitary but may occur in multiple form (hepatic adenomatosis).72 The tumor border is clear and there is usually no capsule, although part of the tumor or its entire circumference may be covered by a ibrous capsule in some cases. In its core, bleeding, necrosis, and scar tissue are seen. Neither portal veins nor bile ducts are found, although bile ductules may develop bile plugs. Recently new genotype/phenotype classiication of hepatic adenoma was released.22 According to it, hepatic adenoma is divided into the following four categories: HNF1αinactivated type, inlammatory type, β-catenin–activated type, and unclassiied type. HNF1α-inactivated adenoma is female predominant and characterized by intratumoral fat deposition. Inlammatory adenoma is female predominant and has potential malignant transformation and steatosis in background liver. The lesions formerly

known as telangiectatic FNH are currently included in inlammatory adenoma.22 β-Catenin–activated adenoma is male predominant, has a higher potential of malignant transformation, and contains vague scar within the tumor. In most cases, nonenhanced CT depicts this tumor as a hypodense mass. Small tumors appear homogeneous, but in general the center shows inhomogeneous attenuation. Coagulum or thrombus may be noted in relatively early stages of ruptured hepatic adenoma as areas of hyperattenuation. In tumors with marked fatty metamorphosis of hepatocytes, a fat-related hypodense area may be seen. In addition, necrotic foci and scar tissue may appear as hypodense areas. Calciication is seen within the tumor in some cases. In the arterial phase of dynamic CT, moderate tumor enhancement is seen.72 HNF1α-inactivated adenoma shows diffuse signal dropout on T1-weighted chemical shift sequence due to steatosis, isosignal or slight hypersignal on T2-weighted images, and moderate enhancement in the arterial phase, with no persistent enhancement in the portal venous and delayed phases (Fig. 44-38). Inlammatory adenoma demonstrates an absence or only focal signal dropout on chemical shift sequences, marked hypersignal on T2-weighted sequences, with a stronger signal in the outer part of the lesions correlating with sinusoidal dilatation areas, and strong arterial enhancement with persistent enhancement in the portal venous and delayed phases151 (Fig. 44-39). In addition, on T2-weighted MRI, a hyperintense signal band in the periphery of the lesion with a center that is isointense to surrounding liver—called a characteristic atoll sign—can be seen.312 MRI indings of β-catenin– activated and unclassiied adenoma are not yet well described. On hepatobiliary-phase Gd-EOB-MRI, more than 90% of hepatic adenomas demonstrated hypointensity relative to the surrounding liver distinctly different from FNH; this is valuable for differential diagnosis.71 However, β-catenin–activated adenoma commonly shows Gd-EOBDTPA uptake with iso- or hyperintensity on hepatobiliary-phase GdEOB-DTPA–enhanced MRI because of OATP1B3(8) overexpression in adenoma cells332 (Fig. 44-40).

Bile Duct Adenoma. Bile duct adenoma is a rare benign epithelial tumor derived from bile duct cells. It is usually located on the surface of the liver. Pathologically it consists of a proliferation of ductules within a connective tissue stroma.4 In reported cases, ultrasonography showed it as a hyperechoic nodule with or without a hypoechoic rim. On dynamic CT or dynamic MRI it shows rapid enhancement in the arterial phase and delayed or prolonged enhancement owing to the ibrous component in the delayed phase.283

Angiomyolipoma. Angiomyolipoma is composed of mature fat, blood vessels, and smooth muscle cells and is not encapsulated.223,304 Immunohistochemical staining of tumor cells reveals HMB-45 positivity.225 On imaging, if the fatty component predominates, it resembles lipoma,224,242 but in general it shows a mixture of a usual solid portion intermingled with a fatty component. Tuberous sclerosis has occasionally been reported to complicate this condition. On nonenhanced CT it appears as a solid mass containing markedly hypodense areas. On MRI, both T1- and T2-weighted images show the same hyperintensity as fatty tissue, with the intensity decreasing with fat suppression.242,329 To detect small volumes of fat, MRI chemical shift imaging (in-phase/opposed-phase) is useful.16 Also, when the vascular component is prominent it appears as a markedly enhanced area on dynamic CT and MRI. However, unlike renal angiomyolipoma, 50% of hepatic angiomyolipomas lack considerable fat content.304 Low-fat tumors may be dificult to differentiate from hypervascular hepatic tumors such as HCC.341 The drainage vein of angiomyolipoma is the hepatic vein, and identifying a perfusing vein communicating with the

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FIG 44-38 Hepatic adenoma in a 37-year-old woman with a 14-year history of oral contraceptive use. There are two mass lesions in segment VII and segment I. On T1-weighted in-phase (A) and opposed-phase (B) MRIs, these tumors show decreased intensity in the opposed phase, which indicates fat deposition in the tumor. C, On T2-weighted MRI, these tumors show slightly hyperintense compared to the liver parenchyma. D, On arterial-phase Gd-EOB-DTPA–enhanced fat-suppressed T1-weighted MRI, these lesions appear isointense compared to the background liver, which indicates slightly early enhancement of these tumors. E, On hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI, these lesions appear hypointense compared to the background liver. The tumor in segment VII was proved to be HNF1α-inactivated adenoma by biopsy. (Courtesy L. Grazioli, University of Brescia, Brescia, Italy.)

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F FIG 44-39 Hepatic adenoma coexisting with focal nodular hyperplasia. There are two mass lesions on segment VII and segment I of the liver. On T1-weighted in-phase (A) and opposed-phase (B) MRIs, these lesions show no decreased intensity in the opposed phase, which indicates no fat deposition in the tumor. C, On T2-weighted MRI the lesion on segment VII appears hyperintense and the lesion on segment I appears isointense compared to the liver. On arterial-phase (D) and late-phase (E) Gd-EOB-DTPA–enhanced fatsuppressed T1-MRI, both lesions show marked enhancement on arterial phase, and the lesion on segment VII shows slightly decreased intensity with rimlike prolonged enhancement; in contrast, the lesion on segment I shows uniform prolonged enhancement. F, On hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI the lesion on segment VII appears hypointense and the lesion on segment I appears hyperintense compared to the background liver. The lesion on segment VII was proved to be inlammatory adenoma, and the lesion on segment I was proved to be focal nodular hyperplasia. (Courtesy L. Grazioli, University of Brescia, Brescia, Italy.)

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FIG 44-40 Hepatic adenoma in a 15-year-old girl. There are multiple masses on the liver. On T1-weighted in-phase (A) and opposed-phase (B) MRIs, these lesions show no decreased intensity in the opposed phase, which indicates no fat deposition in the tumor. C, On T2-weighted MRI, these tumors appear slightly hyperintense compared to the liver parenchyma. On arterial-phase (D) and late-phase (E) Gd-EOB-DTPA–enhanced fat-suppressed T1-weighted MRI, these tumors show marked enhancement on arterial phase and prolonged enhancement on late phase. F, On hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI, these lesions appear hyperintense compared to the background liver. The largest tumor on segment IV was proved to be β-cateninactivated adenoma by biopsy. (Courtesy L. Grazioli, University of Brescia, Brescia, Italy.)

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FIG 44-41 Angiomyolipoma in a 28-year-old woman. A to C, Precontrast CT shows a large lobulated hypodense mass with very hypodense areas internally (arrows in A). B, In the arterial phase the mass is well attenuated, mainly in the peripheral part (arrows). C, In the equilibrium phase the mass is isodense to hypodense (arrows), with dense enhancement of the draining hepatic veins (arrowheads). The central part of the mass shows a decrease in signal in the opposed-phase T1-weighted image (E) (arrow) compared with the in-phase T1-weighted image (D), which indicates the presence of a fatty component in the central part of the mass.

hepatic vein from the tumor center can aid in differentiating angiomyolipoma from fat-containing HCC349 (Fig. 44-41).

Infantile Hemangioendothelioma. This lesion resembles the capillary hemangioma seen in infantile skin and mucosa. Most cases become apparent within 6 months of birth and come to medical attention because of the presence of hepatomegaly and an abdominal mass and occasionally jaundice and congestive heart failure.38 Severe complications include heart failure, hepatic failure, and tumor rupture. If these complications can be avoided, the majority of these tumors regress spontaneously. Infantile hemangioendotheliomas are frequently multiple and range in size from barely discernible to 15 cm. They are well demarcated, and the tumor margin is made up of proliferating endothelial cells and new vessels. The center shows varying degrees of bleeding, ibrosis, necrosis, and calciication.

On nonenhanced CT, a relatively clear hypodense area is seen; on dynamic CT, a staining pattern similar to that of cavernous hemangiomas is noted. Dilated portal and hepatic veins are often visualized (Fig. 44-42). The MRI indings resemble those of hepatic hemangioma.201,251

Leiomyoma. This tumor is extremely rare, and primary hepatic lesions and leiomyosarcoma must be differentiated.51,311 On dynamic CT it is depicted as a hypervascular tumor, and distinguishing leiomyoma from other hypervascular tumors such as HCC may be very dificult.

Mesenchymal Hamartoma. Most mesenchymal hamartomas are seen in children younger than 2 years, and they account for 7% of all primary hepatic tumors in the pediatric population. In almost all cases

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FIG 44-42 Infantile hemangioendothelioma in a newborn (male). A, Precontrast CT shows a large hypodense mass (arrow). B, The arterial phase demonstrates inhomogeneous but marked enhancement (arrow). C, The equilibrium phase demonstrates dense prolonged enhancement with an irregular nonenhanced area (arrow). The density of the main structure of the mass is the same as that of the aorta, indicating large and abundant intratumoral blood spaces.

Pseudolymphoma. Pseudolymphoma (reactive lymphoid hyperplasia) of the liver is a rare benign lesion. Microscopically it consists of hyperplastic lymphoid follicles with distinctive germinal centers and interfollicular areas containing mature lymphocytes and plasma cells. Histologically the lesion mimics Castleman’s lymphoma or low-grade malignant lymphoma of the liver.268 In reported cases it was seen as a hypervascular mass on dynamic CT and MRI186,233 (Fig. 44-44). Pseudolymphoma shows characteristic indings such as a homogeneous parenchymal pattern, vessel-penetrating sign in larger nodules, and a unique enhancement pattern known as perinodular enhancement, which relects increased arterial supply in perinodular hepatic parenchyma due to portal venular stenosis and/or disappearance due to marked lymphoid cell iniltration in perinodular portal tracts.336 The lesions usually regress without medication.233

Miscellaneous Benign Hepatic Tumors. Other uncommon FIG 44-43 Mesenchymal hamartoma in an 8-year-old girl. Postcontrast CT shows a well-demarcated enhanced solid mass with an internal cystic portion (arrow). (Courtesy B.I. Choi, Seoul National University, Seoul, Republic of Korea.)

they are discovered because of an abdominal mass and swelling. They occur more frequently in the right lobe, measure 2 to 29 cm, and are usually solitary and well demarcated, with a few showing pedunculated growth. Macroscopically they are ibrous masses containing small and large cysts; the larger cysts contain a septum.95,272,327 The cysts are illed with a transparent gelatin-like luid. The ibrous portion is edematous, is made up of proliferating ibroblast-like mesenchymal cells, and includes bile ducts and liver parenchyma. Mesenchymal hamartoma with a predominant solid component has also been reported.172 On CT a well-demarcated cystic mass is seen; within or between the cysts, a septum-like structure is found. After administration of contrast medium, this structure within or between the cysts is enhanced (Fig. 44-43). T1-weighted MRIs show hypointensity, and T2-weighted images show marked hyperintensity, probably relecting cystic changes in most cases.327,330

benign tumors include lymphangioma, ibroma, adrenal rest tumor, and pancreatic heterotopia.

Malignant Hepatic Tumors The most common malignant hepatic neoplasms are metastatic tumors. The majority of primary malignant neoplasms originate from hepatocytes and bile duct epithelium. Mesenchymal tumors such as epithelioid hemangioendothelioma, angiosarcoma, primary lymphoma, and other sarcomas are rare.

Hepatocellular Carcinoma Incidence. HCC is one of the most frequent malignancies in the world; it ranks as the ifth most common cause of cancer in men and the seventh in women, with an estimated number of new cases of 520,000 and 230,000, respectively, for men and women in 2008.50 The highest age-adjusted incidence rates (>20 per 100,000) were reported from countries in Southeast Asia and sub-Saharan Africa that are endemic for hepatitis B virus (HBV) infection. Countries in Southern Europe have medium-high incidence rates, while low-incidence areas (10 cm); it is solitary, well demarcated, and lobulated. Necrosis and hemorrhage are seen in the center. A central ibrous scar like that seen in FNH is sometimes present.253,301 On nonenhanced CT, a hypodense solitary mass is seen; in about 50% of cases, central calciication is present. On dynamic CT inhomogeneous enhancement is observed during the arterial phase. A poorly enhanced hypodense area generally relects necrosis. In the equilibrium (or delayed) phase, delayed enhancement of the central scar is seen in about 25% of cases. On MRI the signal intensity is variable but is essentially hypointense on T1- and hyperintense on T2-weighted images. The central scar characteristically shows hypointensity on both T1- and T2-weighted images. SPIO and hepatobiliary agents do not accumulate. The indings on dynamic MRI are the same as those on CT but are more sensitively depicted89,187,276,299 (Fig. 44-64). Differentiation from FNH can be based on these indings, although in some cases the indings are similar.75

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Carcinoma. Cholangiocellular carcinoma (CCC) is a malignant tumor that develops from bile duct epithelium. It is classiied as either intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma and arises from the small intrahepatic bile ducts or hilar bile ducts, respectively. Here, intrahepatic cholangiocarcinoma is described. It has been reported that CCC occurs in those with hepatolithiasis, clonorchiasis or opisthorchiasis, sclerosing cholangitis, ulcerative colitis, hemochromatosis, α1-antitrypsin deiciency, extrahepatic biliary atresia, or Thorotrast exposure. Recently it has been reported that the occurrence of CCC is also associated with HCV infection or hepatitis C–related cirrhosis.212 CCC is often discovered as a huge tan or white tumor that is hard and contains dense ibrous tissue in its center. Histologically CCC consists of glandular adenocarcinoma with abundant sclerosis, with varying amounts of mucin secretion and necrosis noted. The tumors usually show iniltrative growth and a desmoplastic nature, and the contour of the adjacent liver is dented. Intravascular growth is not common, but the vessels and biliary tree are often encased.124,209,212,232 According to the Liver Cancer Study Group of Japan, CCC is divided into three types: mass forming, periductal iniltrating, and intraductal growing.166 The prognosis of the last is much better after surgical resection. On nonenhanced CT, mass-forming CCC is depicted as a hypodense mass. In the arterial phase of dynamic CT, only the periphery of the tumor where viable tumor cells exist is enhanced; the center of the tumor where there is abundant ibrous stroma remains nonenhanced. In the equilibrium phase the center of the tumor may be enhanced (delayed enhancement). In the arterial phase the adjacent liver often shows wedge-shaped enhancement (Fig. 44-65) that relects regional portal or hepatic venous obstruction. Dilatation of the peripheral intrahepatic bile ducts also relects obstruction of the biliary tree by the tumor (see Fig. 44-65). The desmoplasia in the tumor retracts the adjacent liver and depression of the hepatic contour is seen15,126,150,162,252,348 (Fig. 44-66). On MRI the tumor is seen as hypointense on T1- and hyperintense on T2-weighted images, with an irregular contour (see Figs. 44-65 and 44-66). The center of the tumor is more hypointense than the periphery on T2, relecting abundant ibrous stroma. Strongly hyperintense areas on T2-weighted images relect areas with marked mucin secretion or necrosis.169,318 When the tumor iniltrates an intrahepatic bile duct branch, regional cholestasis results, and a hyperintense segment containing the tumor may be seen on T1-weighted images and even more clearly on fat-suppressed T1-weighted images (see Fig. 44-65).64 The indings on dynamic MRI are similar to those on dynamic CT, although more marked early peripheral and delayed central enhancement is seen on dynamic MRI (see Fig. 44-66). Hypervascularity on dynamic CT and MRI can also be demonstrated in some types of CCC with less internal sclerosis. Periductal-iniltrating type and intraductalgrowing type CCC, including intraductal papillary neoplasm of the bile duct (IPNB), are described in Chapter 42. Mucinous carcinoma is a variant of CCC. Histopathologically the tumor consists of myxomatous matrix in which tumor cells are scattered. On ultrasonography the tumor is hyperechoic. On nonenhanced CT the tumor is depicted as a deinitely hypodense mass. The density of the tumor is slightly higher than that of water. During the arterial phase of dynamic CT, the periphery of the tumor demonstrates enhancement that gradually spreads toward the center during the portal and equilibrium phases. It shows marked hypointensity on T1and marked hyperintensity on T2-weighted images. Dynamic MRI indings are similar to those on dynamic CT but are more prominent; in the delayed phase when the tumor is relatively small, diffuse and deinite enhancement of the entire tumor can be seen79,309 (Fig. 44-67).

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FIG 44-64 Fibrolamellar carcinoma in a 24-year-old man. A, Precontrast CT demonstrates an inhomogeneous hypodense mass with punctate calciications within a central scar (arrow). B, Arterial-phase CT shows deinite enhancement, with dilated feeding arteries except for the central scar and necrotic portions (arrow). C, Nonnecrotic portions and the central scar exhibit delayed enhancement in the equilibrium phase (arrow). D, T1-weighted image demonstrates an inhomogeneous hypointense mass with a more hypointense central scar (arrow). E, On the T2-weighted image the mass shows inhomogeneous hyperintensity and the scar remains hypointense (arrow). Arrowheads in D and E indicate internal hemorrhagic necrosis. (Courtesy M. Satake, National Cancer Center East, Japan.)

These indings mimic those of cavernous hemangioma; the arterial phase of dynamic CT or MRI should be used for differentiation.309 Metastasis from mucinous carcinoma of the colon shows similar features.

Combined Hepatocellular and Cholangiocellular Carcinoma. Combined hepatocellular and cholangiocellular carcinoma is deined as a tumor containing unequivocal intimately mixed elements of both HCC and CCC.297 It has areas of HCC with trabecular growth as well as areas of gland formation with ibrous stroma and mucin production. Combined HCC and CCC is considered a subtype of HCC.282 A hepatic stem cell origin of this tumor is now suspected because foci of intermediate morphology are seen at the interface of HCC and CCC in many cases.77,298 These with stem cell features are subdivided into typical, intermediate-cell, and cholangiolocellular subtypes (WHO classiication).297

Both typical HCC areas and typical CCC areas are found within a single tumor. The HCC areas are hypervascular and show rapid runoff of contrast material. In contrast, the CCC areas are hypovascular and show delayed enhancement in the equivalent phase of postcontrast CT or MRI.10,46,57 When the HCC and CCC areas are clearly separated, the correct diagnosis can be made. However, the imaging indings of those with stem cell features are variable. Distinguishing poorly differentiated HCC, scirrhous-type HCC, CCC, and metastatic adenocarcinoma may be dificult.

Cholangiolocellular Carcinoma. Cholangiolocellular carcinoma was irst described by Steiner and deined as a tumor that originates from the Hering duct or cholangiole of the liver.277 The Hering duct is located at the connection of bile canaliculi, which is composed of hepatocytes, and the cholangiole, which is the irst component of the intrahepatic bile duct. Thus the component cells of the Hering duct

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E FIG 44-65 Mass-forming type of cholangiocellular carcinoma (intrahepatic cholangiocarcinoma) with cholestasis and Zhan’s infarction of the left lobe of the liver. A, Precontrast CT scans demonstrate a hypodense mass (arrow) with dilated intrahepatic bile ducts. B, The arterial phase reveals faint peripheral enhancement of the tumor (arrow) and segmental staining of the left lobe due to associated left portal vein obstruction. C, In the equilibrium phase the lesion shows hypodensity (arrow). Delayed enhancement caused by abundant ibrous tissue in the tumor is not prominent in this case. D, T1-weighted MRI demonstrates a hypointense nodule (arrow) and segmental hyperintensity in the left lobe due to cholestasis. E, T2-weighted MRI shows the nodule as hyperintense (arrow). The diffuse hypodensity on precontrast CT and hyperintensity on T2-weighted MRI in the left lobe may indicate Zhan’s infarction due to portal vein obstruction.

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FIG 44-66 Mass-forming type of cholangiocellular carcinoma. A, T1-weighted MRI demonstrates a hypointense mass with depression of the adjacent liver surface (arrow). B, T2-weighted MRI demonstrates a hyperintense mass with markedly hyperintense central necrosis (arrow). C and D, Dynamic contrast-enhanced T1-weighted MRI reveals peripheral enhancement in the arterial phase (C) (arrow) and internal delayed enhancement in the equilibrium phase (D) (arrow).

are thought to have intermediate features between hepatocyte and bile duct epithelium. Histopathologically, cholangiolocellular carcinoma tends to show a replacing growth pattern that is not common in typical CCC but is common in HCC. The concept of “bile ductular carcinoma” was proposed recently.146 In the new WHO classiication, this is included in a subtype of combined HCC and CCC.297 Based on our experience, cholangiolocellular carcinoma is hypodense on precontrast CT, shows slight enhancement with a less-enhancing central part in the arterial phase of dynamic CT, and shows delayed enhancement in the central part of the tumor in the equilibrium phase (Fig. 44-68). Intratumoral portal tracts can often be seen.14,203

Biliary Cystadenoma and Cystadenocarcinoma. Biliary cystadenoma and cystadenocarcinoma are rare solitary multilocular cystic masses that resemble mucinous cystic tumors of the pancreas. Cystadenoma is a large cystic neoplasm with internal septation and papillary projections. The locules are lined with columnar epithelium, and benignity and malignancy cannot be grossly differentiated. Papillary projections are more frequently present in malignant cases. Adenoma and adenocarcinoma may be intermingled in some cases, and

cystadenoma is considered a premalignant lesion. The locules contain turbid, purulent, or bloody mucin. Ovarian-like stroma is usually found in females.28,60,96,144,199,346 The locules of hepatobiliary cystadenoma and cystadenocarcinoma seldom communicate with the biliary tree. When such a communication exists, the distal and proximal biliary tree is dilated because of mucin. This type of tumor can be distinguished from the common cystadenoma or cystadenocarcinoma and is referred to as a mucin-hypersecreting bile duct tumor (or cholangiocarcinoma). It is considered the intrahepatic counterpart of intrapancreatic mucinous neoplasms.9,164,346 On imaging, biliary cystadenoma or adenocarcinoma appears as a unilocular or multilocular cystic mass with a thin wall and papillary projections. On nonenhanced CT the tumor is a uniformly hypodense mass. The density of the contents of the cyst is often greater than that of simple hepatic or renal cysts. Focal calciication of the cyst wall may be seen. On postcontrast CT the wall and septa of the tumor, as well as the papillary projections, are enhanced28,96,144,199 (Figs. 44-69 and 44-70). On T1-weighted images the tumor appears as a hypointense cystic mass. The intensity of the content of each locule may differ and is

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D FIG 44-67 Mucinous carcinoma (a variant of cholangiocellular carcinoma). A to C, Precontrast CT shows a deinitely hypodense mass (arrow in A). It demonstrates gradual enhancement (arrow) from the periphery of the tumor through the arterial phase (B) to the equilibrium phase (C). D, T2-weighted MRI demonstrates the lesion as a deinitely hyperintense mass (arrow) because of abundant intratumoral mucin.

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FIG 44-68 Cholangiolocellular carcinoma (bile ductular carcinoma). A, Precontrast CT shows a hypodense mass (arrow). B, Postcontrast CT demonstrates slight enhancement, more prominent in the periphery in the arterial phase (arrow), and delayed enhancement in the central part of the tumor in the equilibrium phase. Dilated bile ducts are observed within the tumor, which represents the presence of intratumoral portal tracts (C) (arrow).

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FIG 44-69 Cystadenoma with ovarian stroma in a 52-year-old woman. A, Arterial phase of dynamic CT shows a large cystic mass (arrow) with a small internal daughter cyst (arrowhead) projecting from the wall of the main cyst. Cyst walls are well enhanced, and minute enhanced projections are seen in the daughter cyst. B, On T1-weighted MRI the main cyst demonstrates hyperintensity comparable to mucin with a high protein content (arrow). In contrast the daughter cyst shows hypointensity similar to cerebrospinal luid (arrowhead). C, On T2-weighted MRI, both cysts demonstrate deinite hyperintensity (arrow and arrowhead).

higher than that of cerebrospinal luid. On T2-weighted images the intensity of the content is very high but varies depending on the nature of the luid.60,158 For differentiation from cystic intraductal papillary neoplasm of the bile duct, visualization of the communication between the dilated bile duct and the surrounding liver, including proximal intrahepatic bile ducts, is valuable.9,164,346

Hepatoblastoma. Hepatoblastoma is a malignant hepatocellular

FIG 44-70 Cystadenocarcinoma with ovarian stroma in a 65-year-old woman. Postcontrast CT shows a large cystic mass with enhanced papillary projections from the wall (arrows).

tumor of childhood. It seldom occurs after age 5 years and is the most common hepatic tumor in children younger than 5. Three quarters of patients are male. Like other tumors of childhood, genetic abnormalities are related to development of the disease. It is known that patients with hepatoblastoma also have Beckwith-Wiedemann syndrome, familial adenomatous polyposis coli, cardiovascular anomalies, diaphragmatic defects, malrotation of the intestine, anomalies of the urinary tract, and Down’s syndrome. Most of these tumors are detected after a parent notices abdominal enlargement. Serum AFP is elevated in most cases. Grossly, hepatoblastomas are often huge and single. The surrounding liver is not cirrhotic. Histopathologically, hepatoblastoma can be classiied as either epithelial type or mixed epithelial and

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D FIG 44-71 Hepatoblastoma in a 3-year-old boy. A, Precontrast CT shows a well-demarcated heterogeneous hypodense mass (arrow). B, There is heterogeneous internal enhancement on postcontrast CT (arrow). The mass (arrow) demonstrates heterogeneous hypointensity on T1- (C) and hyperintensity on T2-weighted MRI (D).

mesenchymal type. The epithelial component is divided into two subtypes: embryonal and fetal.39,241 On nonenhanced CT, hepatoblastoma is a huge hypodense mass with occasional calciication. On dynamic CT it becomes heterogeneously hyperdense in the arterial phase and hypodense in the equilibrium phase. A typical lobulated appearance is more clearly seen after administration of contrast medium. On MRI these tumors show hypointensity on T1- and hyperintensity on T2-weighted images. Hemosiderin deposition associated with intratumoral hemorrhage is sometimes present when hypointense parts are noted on both T2-weighted and long-TE (echo time) gradient echo images. Fibrous septa may be seen on CT or MRI25,39,241 (Fig. 44-71).

Epithelioid Hemangioendothelioma. Epithelioid hemangioendothelioma (EHE) is a vascular tumor that occurs in the lung, bone, and soft tissue. Most cases are slowly progressive; thus the clinical behavior is considered low-grade malignant. Most cases occur in adults, two thirds of them in women. EHE tends to be located in the subcapsular area of the liver. The surface of the liver is often retracted by the tumor. Marked ibrous tissue and portal tract remnants are seen in the center of the tumor, with an increased number of cells (mainly epithelioid) found in the surrounding tissues. The invasive front of EHE iniltrates hepatic sinusoids and small vessels. In the center of the tumor there is dense hyalinized ibrous tissue. The tumor has abundant stromal

matrix and seems cartilaginous. Calciication is sometimes seen. The tumors tend to be multiple and often fuse in the subcapsular areas over the course of the disease, resulting in central hypertrophy. These changes are characteristic of EHE and are useful in making the imaging diagnosis.59,171,247,323 Nonenhanced CT depicts hypodense nodules in the subcapsular area of the liver. Some lesions show calciication. In the arterial phase of dynamic CT, no deinite enhancement is apparent. On postcontrast CT the tumor shows slight enhancement and becomes somewhat indistinct. The contour of the liver is retracted by the tumor59,189,247 (Fig. 44-72). On MRI a variety of signal intensities are reported. On T1-weighted images EHE usually demonstrates hypointensity. On T2-weighted images moderate hyperintensity is shown, with a more hyperintense core (target sign; see Fig. 44-72). On dynamic MRI the tumor demonstrates a moderate peripheral enhancement and delayed central enhancement. In advanced cases a diffusely coalescent tumor in the subcapsular area and central hypertrophy of the liver are observed (see Fig. 44-72).167,313 In the early stage a solitary nodule or a few nodules constituting a nonspeciic solid mass mimicking cholangiocarcinoma and metastatic liver cancer can be seen.

Angiosarcoma. Angiosarcoma is a rare malignant hepatic tumor but is the most frequently encountered malignant mesenchymal tumor of the liver. It is derived from endothelial cells. Most patients are older

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FIG 44-72 Epithelioid hemangioendothelioma. A, Precontrast CT scan depicts hypodense nodules in the subcapsular area of the liver (arrows). Coalescent masses are also shown. B, In the arterial phase, no deinite enhancement is apparent. C, On postcontrast CT the tumor shows slight delayed enhancement and some lesions become somewhat indistinct. The contour of the liver is retracted by the tumor. Central hypertrophy of the liver is also evident. D, T1-weighted MRI demonstrates hypointense masses (arrows). E, On T2-weighted MRI they are visualized as hyperintense nodules with more hyperintense cores (arrows).

men who have a history of exposure to toxins such as vinyl chloride monomer, Thorotrast, arsenic, or anabolic steroids. Grossly, angiosarcoma consists of multiple masses spreading throughout the liver. They vary in size and can become massive. In the center of these tumors, necrosis, thrombosis, or hemorrhage may be found. Most cases are diagnosed in the advanced stage, with hepatic failure and intraperitoneal hemorrhage due to rupture seen in many cases. Intrahepatic tumors range from solitary to diffuse.30,145 On nonenhanced CT, angiosarcomas are seen as heterogeneous hypodense masses. Because of hemorrhage, the center may appear hyperdense. In cases with associated intraperitoneal bleeding, a hyperdense area due to acute clot adjacent to the tumor may be noted. On dynamic CT these tumors are well enhanced in the arterial phase, occasionally showing peripheral nodular enhancement and progressive and delayed illing enhancement on the delayed phase. Although the enhancement pattern of the mass is slightly different from the typical enhancement of hemangiomas, when the tumor is small and well demarcated it resembles cavernous hemangioma. However, in many cases these characteristics are absent, and instead, hypovascularity or ringlike enhancement is evident. T1-weighted images show a variety of hyperintense areas because of the presence of hemorrhage in basically hypointense masses. On T2-weighted images marked heterogeneous hyperintensity is seen

(Fig. 44-73). Fluid-luid levels and septation may be seen in some cases.82,103,145,239

Undifferentiated Embryonal Sarcoma. Undifferentiated embryonal sarcoma is a rare malignant neoplasm that occurs in childhood and adolescence. It grows rapidly, and cystic degeneration, intratumoral hemorrhage, or necrosis frequently occurs. Serum AFP is not elevated. Grossly it is a huge mass composed of cystic, gelatinous, red hemorrhagic and yellow necrotic areas, with a pseudocapsule made up of ibrous tissue. Histologically, viable cells are located at the edge of the tumor; the remaining portion is necrotic and accounts for the majority of the tumor. The tumor cells are stellate or spindle shaped with myxoid or ibrous stroma. The resemblance to mesenchymal hamartoma suggests that undifferentiated embryonal sarcoma is its malignant counterpart.29,199 On nonenhanced CT the tumor is depicted as a huge wellcircumscribed mass with clustering of several central cystic and peripheral solid components. The contour of the tumor has clefts and the tumor is lobulated. Postcontrast CT clearly shows the demarcation of the central cystic and peripheral solid areas. On T2-weighted images the cystic components are very hyperintense. On T1-weighted images the tumor is a hypointense mass with hyperintense spots suggesting intratumoral hemorrhage29,199,244,334 (Fig. 44-74).

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FIG 44-73 Angiosarcoma in a 67-year-old man. A, On precontrast CT, multiple nodules are seen as heterogeneous hypodense masses (arrows). Hyperdense areas are due to internal hemorrhage. Peripheral nodular enhancement in the arterial phase (B) and progressive and delayed illing enhancement in the equilibrium or delayed phase (C) are also visualized. D, On T1-weighted MRI, hyperintense areas due to hemorrhage are evident in basically hypointense masses (arrows). E, On T2-weighted MRI, marked heterogeneous hyperintensity is visualized (arrows).

Primary Hepatic Malignant Lymphoma. Primary hepatic lymphoma is rare, although the liver is frequently involved by systemic malignant lymphoma. In most cases the cause is unknown, but associations with hepatitis C, hepatitis B, Epstein-Barr virus infection, and immunocompromising conditions have been described. The tumor is usually solitary, and a splenic mass is often associated. On CT it is depicted as a slightly enhanced, homogeneously hypodense nodule.256 Another characteristic feature is iniltrative growth showing hardly any mass effect. When imaging studies reveal piercing of the native portal tracts in the tumor, the possibility of lymphoma must be considered.11 The histologic indings are extremely varied, and in some tumors with extensive ibrous interstitium between tumor cells, postcontrast CT shows delayed enhancement.20 On MRI the tumor is well demarcated and shows homogeneous hypointensity on T1- and homogeneous hyperintensity on T2-weighted images in most cases.322,324 It may be seen along the porta hepatis.94

Metastatic Liver Tumor. The most common liver metastasis is from the gastrointestinal tract. Adenocarcinoma with an abundant ibrous interstitium (scirrhous cancer) is characterized by the presence of abundant viable cancer cells in the peripheral portion of the tumor and ibrous interstitium and necrosis in its center. In most cases of medullary cancer metastases, the center also becomes

necrotic, although small lesions may lack necrotic foci. On both nonenhanced and postcontrast CT, the lesion is depicted as a nonspeciic hypodense nodule. In the arterial phase of dynamic CT the peripheral hypercellular portion shows slight ringlike or donut-like enhancement. In the equilibrium phase it becomes hypodense, whereas ibrous necrotic tissue in the center of the tumor shows delayed enhancement65,206,295,296,337 (Fig. 44-75). In liver metastasis from medullary carcinoma, diffuse enhancement of the entire tumor can be seen. The most common hypervascular metastatic liver tumors are those derived from endocrine cancers (e.g., islet cell tumors, renal cell carcinoma, carcinoid).219,275 Metastatic liver cancer appears hypointense on T1- and hyperintense on T2-weighted images. Necrotic changes in the central portion are depicted as more hyperintense on T2-weighted images, and a bull’s-eye pattern may be seen, as on ultrasonography (Fig. 44-76). Contrast-enhanced MRI depicts the indings of dynamic CT more sensitively.65,264 In liver metastases from colon cancer, T2-weighted images may show the center to be hypointense (Fig. 44-77). The histologic background is considered to be ibrosis.234 Liver metastases from colon and stomach mucinous carcinoma often have imaging features similar to those of the mucinous carcinoma variant of CCC (see earlier under “Mucinous Carcinoma”) (Fig. 44-78). Because melanin is a paramagnetic substance, liver metastases from melanoma

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FIG 44-74 Undifferentiated embryonal sarcoma with diffuse myxoid change in a 15-year-old girl. A, Arterial phase of dynamic CT shows a large hypodense mass with internal inhomogeneous enhancement (arrow). B, T1-weighted MRI demonstrates an extremely hypodense mass with internal hyperintense areas due to hemorrhage (arrow). C, T2-weighted MRI visualizes a deinitely hyperintense mass with internal septation (arrow). Cystic changes are not seen in this case. (Courtesy Y. Kodama, Hokkaido University, Japan.)

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FIG 44-75 Liver metastasis from colon cancer. A, Precontrast CT demonstrates two hypodense nodules (arrows). B, Arterial phase shows peripheral enhancement (arrows). C, In the equilibrium phase, diffuse faint enhancement in the tumors is visualized (arrows).

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typically appear hyperintense on T1- and hypointense on T2-weighted images121 (Fig. 44-79). Metastatic liver cancer forms nodules as a rule, and their distribution and size vary to some extent according to the type of underlying malignancy. For example, liver metastases from pancreatic cancer are

usually small and uniform and are distributed throughout the liver, whereas those from gallbladder cancer tend to cluster in the gallbladder fossa. In breast cancer, micronodules tend to be distributed diffusely. Liver metastases from smooth muscle sarcomas often show prominent liquefaction necrosis in their centers257 (Fig. 44-80). In the case of lymphogenic metastasis, tumor iniltration within the liver and along the portal tracts is sometimes seen; this is observed most frequently with bile duct and gallbladder cancers but also with gastric cancer, pancreatic cancer, and malignant lymphoma. In portal tract iniltration, T2-weighted images show a hyperintense area around the portal vein105,181,281 (Fig. 44-81). Peritoneal dissemination of cancer involves the subcapsular area of the liver, appearing as an intrahepatic mass in some cases. This is often seen in ovarian cancer.287

FIG 44-76 Liver metastasis from colon cancer. T2-weighted image shows a hyperintense nodule with a more hyperintense central portion (bull’s-eye pattern).

FIG 44-77 Liver metastasis from colon cancer. T2-weighted image

A

shows a nodule with internal hypointensity and a hyperintense rim (arrow).

B FIG 44-78 Mucinous liver metastasis from colon cancer. A, Precontrast CT shows a deinitely hypodense mass with a calciic deposit (arrow). B, T2-weighted MRI demonstrates an extremely hyperintense mass (arrow).

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B FIG 44-79 Multiple liver metastases from malignant melanoma. A, T1-weighted image shows multiple hyperintense nodules (arrows). B, On the T2-weighted image they demonstrate hypointensity (arrows).

FIG 44-81 Pancreatic cancer invading the liver through the portal FIG 44-80 Cystic hepatic metastases from gastrointestinal stromal tumor of the small bowel. Postcontrast CT shows multiple nonenhanced masses with enhanced irregular rims (necrotic masses; arrows).

tracts. T2-weighted image shows periportal extension of the tumor as a hyperintense band along the portal tracts (arrows).

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A FIG 44-82 Moderately to poorly differentiated HCC. A, Postcontrast CT shows a moderately to poorly differentiated mass (arrow). B, PET CT shows a deinite accumulation of FDG (arrow).

Miscellaneous Malignant Tumors. Other primary malignant tumors include carcinoid tumors, other types of sarcomas such as leiomyosarcoma and liposarcoma, and malignant ibrous histiocytoma. These are all very rare.

IMAGING TECHNIQUES FDG PET in the Diagnosis of Liver Tumors There are two major goals when using luorodeoxyglucose (FDG) positron emission tomography (PET) for liver imaging: to detect and characterize the liver tumor, and to monitor the effect of therapy. Malignant tumor cells generally show an overexpression of glucose transporters on cell membranes, resulting in increased uptake of glucose in tumor cells. For accumulation of FDG in tumor cells to occur, overexpression of hexokinase and lower expression of glucose6-phosphatase are necessary. However, the activity of glucose-6-phosphatase is high in both normal liver and well-differentiated HCC, and FDG PET is not sensitive for the diagnosis of HCC.266 However, Trojan et al. noted that in patients with moderately or poorly differentiated HCC, tumors larger than 5 cm, or markedly elevated AFP levels, FDG PET may contribute to effective noninvasive staging302 (Fig. 44-82). Although limitations include false-positive results in a minority of abscesses and false-negative results in well-differentiated HCCs, PET is useful in estimating the grade of malignancy, tumor staging, detecting recurrence, and monitoring response to therapy for most HCCs.40,165,325 FDG PET is also useful in detecting and staging both hilar and peripheral cholangiocarcinoma.130,250 For detection of colorectal liver metastases, FDG PET has a signiicantly higher sensitivity on a per-patient basis, but not on a per-lesion basis, than CT and MRI23 (Fig. 44-83). For detection of liver metastases from pancreatic tumors, the diagnostic accuracy of FDG PET is 90%, which is comparable to ultrasonography or CT.210 FDG PET can also be used to evaluate therapeutic interventions. Use of FDG PET in combination with CT at follow-up of radiofrequency ablation of primary and secondary liver tumors may lead to

A

B FIG 44-83 Metastasis from colon cancer. A, Postcontrast CT demonstrates a small metastasis (arrow) and associated hepatic cysts (arrowhead). B, PET CT clearly visualizes the lesion (arrow).

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REFERENCES

FIG 44-84 Metastasis from colon cancer. DWI clearly demonstrates multiple liver metastases as hyperintense lesions.

earlier detection of tumor recurrence than use of contrast-enhanced CT alone.24 It is also valuable to evaluate the therapeutic effects of transarterial chemoembolization/radioembolization and sorafenib therapy for HCCs.153,254,258,273 FDG PET has a potential role in evaluating the antitumor effect of chemotherapy in patients with liver metastases from colorectal cancer.52

Diffusion-Weighted Imaging in the Diagnosis of Focal Liver Lesions Based on recent advances in MRI technique, diffusion-weighted imaging (DWI) has been applied to liver examinations.208,342 Detection of HCCs by DWI was around 50% in the analysis of explanted livers,78 because early HCC and well-differentiated HCC are not well visualized on DWI images. However, apparent diffusion coeficient (ADC) measurement with DWI may help estimate the grade of malignancy of hepatocellular nodules during hepatocarcinogenesis. ADCs tend to decrease as the grade of malignancy of the nodules rise from early to poorly differentiated HCC, but with signiicant overlaps.221 DWI is valuable to diagnose an early-stage hypovascular HCC when it shows nonspeciic imaging features on hepatobiliary-phase Gd-EOB-DTPA–enhanced MRI (e.g., hyperintensity on DWI strongly indicates HCC).237 Metastatic liver cancers, including colorectal hepatic metastases, have higher ADCs compared with background liver140 and are well depicted as hyperintense nodules on DWI (Fig. 44-84). Gd-EOB-DTPA MRI combined with DWI is highly effective for detection and characterization of metastases from colorectal cancer.36 ADC measured by DWI is valuable for differential diagnosis. Hepatic cysts can be discriminated from other solid mass lesions with a cutoff of 2.5 × 10−3 mm2/sec at b values of 400 to 1000 sec/mm2. However, although ADCs tend to decrease in the order of cavernous hemangiomas, HCCs, and metastases, there are substantial overlaps among them.68 One major role of DWI in liver imaging is to detect and predict the effect of therapy on liver tumors (see Fig. 33-50). A higher pretreatment ADC value in a metastatic liver tumor is predictive of a poor response to chemotherapy, and a signiicant increase in ADC value is observed in metastatic lesions that respond to chemotherapy.141 Increase in the ADC value after yttrium-90 microsphere treatment of HCC may predict therapeutic response in the early posttreatment period.113

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45 Liver Transplantation Raj M. Paspulati

HISTORY Transplantation of the liver is the deinitive treatment for irreversible acute and chronic liver disease. The irst successful liver transplant was performed by Starlz in 1967 on a patient with hepatocellular carcinoma, who survived for more than 1 year.130 The development of cyclosporine in 1970, followed by other immunosuppressant agents and improved surgical techniques, has signiicantly improved the survival rates of liver transplant patients, leading to the acceptance of liver transplantation into clinical practice and the creation of several transplant centers in the United States and worldwide. The increased success of liver transplants led to a long waiting list of potential liver recipients owing to a shortage of cadaver livers. This shortage of cadaver livers led to the development of split cadaver transplantation and livingdonor liver transplantation (LDLT). According to data from the Organ Procurement and Transplantation Network (optn.org), from January 1988 to July 2015, 137,039 liver transplants were performed in the United States, 5519 of which were living-donor transplants.152 The United Network for Organ Sharing (UNOS) is a nonproit scientiic organization that acts as the only organ procurement network in the United States. Owing to the long waiting list, the allocation of donor livers is based on the principle that the sickest patient who has been waiting the longest is given priority. Disease severity was initially based on the Child-Turcotte-Pugh score, which had several limitations. The current severity assessment is based on the Model for End-Stage Liver Disease (MELD) scoring system, which includes three parameters: serum bilirubin, international normalized ratio, and serum creatinine. The MELD scoring system is a more accurate index of disease severity and a better assessment of mortality risk in patients with end-stage liver disease.16,34,158

INDICATIONS FOR LIVER TRANSPLANTATION The major indications for liver transplantation are hepatic decompensation secondary to chronic liver disease, acute liver failure, primary hepatic malignancy, and inborn errors of metabolism. Several other miscellaneous indications are listed in Box 45-1. Acute liver failure accounts for 5% to 6% of all liver transplants in the United States.94,144 Chronic liver disease due to hepatitis C infection is the leading indication for liver transplantation in the United States.113 Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation. Chronic liver disease and cirrhosis are associated with a 2% to 8% annual incidence of HCC; patients with cirrhosis associated with HCC are given higher priority for liver transplantation.7,94,122 However, only patients with early HCC without vascular invasion or metastasis are suitable candidates. Early HCC, as deined by the Milan criteria,

includes a single HCC lesion less than 5 cm or no more than three lesions, all of which are less than 3 cm90 (Fig. 45-1). The 5-year survival rate after transplantation in patients with HCC fulilling these selection criteria is reported to be 75%. There are conlicting results in patients with multifocal and diffuse iniltrative HCC (Fig. 45-2). Locoregional therapy using radiofrequency ablation, cryoablation, or chemoembolization is being used to reduce the tumor burden in these patients while they await liver transplantation9,35,49,83,126 (Fig. 45-3). Less common hepatic malignancies with promising survival rates following transplantation include ibrolamellar carcinoma, epithelioid hemangioendothelioma, and hepatoblastoma.4,60,78 Patients with hemangiosarcoma and hepatic metastases, with the exception of metastases from neuroendocrine tumors, have poor outcomes after transplantation. Unresectable cholangiocarcinoma is also treated by liver transplantation after downstaging with aggressive chemoradiation treatment.49,72,94,117,153

CONTRAINDICATIONS TO LIVER TRANSPLANTATION The absolute and relative contraindications for liver transplantation are outlined in Box 45-2. Brain death, extrahepatic malignancy or metastatic disease (Fig. 45-4), and poor compliance are the main absolute contraindications. Portal vein thrombosis is no longer an absolute contraindication to liver transplantation but remains a poor prognostic indicator for postoperative graft function (Fig. 45-5; see also Fig. 45-2). Cholangiocarcinoma without predisposing primary sclerosing cholangitis has a 5-year survival rate of 2% to 43% following curative surgical resection. Patients with unresectable cholangiocarcinoma or preexisting primary sclerosing cholangitis should be considered for liver transplantation.85 Inoperable hilar cholangiocarcinoma treated with neoadjuvant chemoradiation followed by liver transplantation has 1-, 3-, and 5-year survival rates of 92%, 82%, and 82%, respectively.47,100,110,132 Accurate staging of cholangiocarcinoma with crosssectional imaging is crucial for proper patient selection. HIV infection is no longer a contraindication to liver transplantation in patients with end-stage liver disease. Selection of patients is based on CD4 cell count and a viral load that is suppressible with antiretroviral treatment.92,94

EVALUATION OF THE DONOR Liver donors for LDLT are assessed for medical, psychosocial, and inancial suitability. The medical evaluation includes a routine presurgical clinical assessment and laboratory and serologic tests. Preoperative imaging is mandatory for the exclusion of focal or diffuse liver lesions and identiication of variations in biliary and vascular anatomy. Assessment of segmental and total liver volumes of both recipient and

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donor is necessary to ensure adequacy of the donor liver size. Contrastenhanced computed tomography (CT) and magnetic resonance imaging (MRI) with multiplanar reconstruction (MPR) are excellent for pretransplant evaluation of the liver in living-donor candidates. MRI is more speciic for the characterization of focal liver lesions and

Indications for Liver Transplantation BOX 45-1

Cirrhosis Chronic hepatitis B and C Alcoholic liver disease Autoimmune hepatitis Cryptogenic cirrhosis Primary biliary cirrhosis Primary sclerosing cholangitis

the diagnosis of hepatic steatosis. Evaluation of the donor liver for the presence and extent of steatosis is essential because fatty change carries a high risk of postoperative liver dysfunction in donors and graft nonfunction in recipients (Fig. 45-6). The acceptable upper limit of steatosis in the donor liver is 30%.54,71,125 The minimum graft volume required for adequate hepatic function in the recipient is reported to be 30% to 40% of the recipient weight. A donor remnant liver volume of greater than 30% of the original volume is necessary to maintain suficient liver function in the donor.80,82,154 The reported incidence of variations in the portal vein, hepatic artery, and biliary anatomy is 14%, 29%, and 44%, respectively. Prior knowledge of these variations

Contraindications to Liver Transplantation BOX 45-2

Absolute Contraindications MELD score < 15 Advanced cardiopulmonary disease Brain death Extrahepatic malignancy Angiosarcoma of the liver Uncontrolled sepsis Persistent noncompliance Active alcohol and substance abuse Vascular variations incompatible with transplantation Anatomic abnormality that precludes liver transplantation

Acute Liver Failure Hepatitis A and B Drugs and toxins Metabolic Diseases α1-Antitrypsin deiciency Hemochromatosis Wilson’s disease Glycogen storage disorders Malignancy Hepatocellular carcinoma Metastases from neuroendocrine tumors Hepatoblastoma Hepatic epithelioid hemangioendothelioma Cholangiocarcinoma* Miscellaneous Nonalcoholic fatty liver disease Polycystic liver disease Budd-Chiari syndrome *Cholangiocarcinoma is no longer a contraindication for liver transplantation, provided that proper selection criteria are followed.

A

Relative Contraindications HIV infection* Portal vein thrombosis† Hepatopulmonary syndrome Advanced age Morbid obesity Lack of adequate social support system *HIV infection is no longer an absolute contraindication; patient selection is based on CD4 count and HIV-1 RNA viral load. † The extent of portal vein thrombosis should be evaluated by pretransplant imaging. Portal vein thrombosis alone is not a contraindication, but extensive thrombosis with involvement of the superior mesenteric vein is a contraindication.

B FIG 45-1 Hepatocellular carcinomas less than 5 cm in a liver before transplantation. A, Three hyperintense lesions (arrows) are visible on a pre-Gd T1-weighted image. B, Post-Gd T1-weighted image in the equilibrium phase shows central washout with peripheral enhancing capsules of the lesions (arrows).

CHAPTER 45

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B FIG 45-2 Diffuse iniltrating hepatocellular carcinoma in a liver before transplantation. Post-Gd axial (A) and coronal (B) MRI in the portal venous phase demonstrate a diffuse iniltrating mass (arrowheads) in the right lobe, with portal vein tumor thrombosis (arrows).

A

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D FIG 45-3 Multifocal hepatocellular carcinoma in a liver before transplantation. Axial (A) and coronal (B) contrast-enhanced CT images demonstrate multiple focal enhancing lesions (arrows in A). Arterial-phase contrast-enhanced CT images before (C) and after (D) chemoembolization demonstrate right and left hepatic arteries (arrows) and embolized tumor (arrowheads in D).

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B FIG 45-4 Hepatocellular carcinoma with adrenal metastases in a liver before transplantation. A, Axial contrast-enhanced MRI in the arterial phase demonstrates a heterogeneously enhancing mass (arrowheads) in the right lobe and a new focal enhancing nodule (arrow) in the right adrenal gland. B, Axial contrastenhanced MRI in the portal venous phase shows an enhancing right adrenal nodule (arrow).

LIVER TRV MPV

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D FIG 45-5 Cirrhosis with portal vein thrombosis. A, Grayscale US demonstrates an enlarged main portal vein (arrows). B, Color-low Doppler shows no low in the main portal vein (white arrow) with periportal collateral veins (black arrow). Coronal (C) and axial (D) post-Gd MRI shows a thrombosed main portal vein (white arrows) and periportal collateral veins (black arrows).

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B FIG 45-6 Hepatic steatosis of a donor liver. In-phase (A) and opposed-phase (B) T1-weighted images demonstrate a diffuse drop in signal intensity of the liver on the opposed-phase image.

is useful to the operating surgeon in planning the vascular and biliary anastomosis because most posttransplantation vascular complications occur at the anastomosis.21,138 In adult-to-adult LDLT, the hepatectomy plane is to the right of the middle hepatic vein and involves preservation of the segment artery, left portal vein, and middle hepatic vein.

Hepatic Artery Anatomy and Variations The standard hepatic artery anatomy, with proper branching to right and left hepatic arteries, is seen in approximately 55% of patients. The hepatic artery variations were irst classiied by Michels in 1966.91 The most common variations described are the replaced or accessory right hepatic artery (RHA), arising from the superior mesenteric artery, and the replaced or accessory left hepatic artery (LHA), arising from the left gastric artery (Fig. 45-7A to D). A replaced RHA or LHA is not an absolute contraindication for donor selection, but additional measures must be taken to perform a safe anastomosis. An accessory RHA or LHA, in contrast, needs dual anastomoses in the recipient unless there is an intraparenchymal anastomosis between the two arteries (see Fig. 45-7E). A short RHA in the donor is signiicant because it makes performing the anastomosis in the recipient dificult and requires extensive reconstructive surgery. Origin of the RHA or LHA from the common hepatic artery proximal to the gastroduodenal artery can compromise perfusion of the donor stomach and duodenum after ligation of the common hepatic artery. Another signiicant variation in the donor is origin of the artery to segment 4 from the RHA (middle hepatic artery). Identiication of this arterial branch to segment 4 is important in adult-to-adult LDLT because the hepatectomy line would cross the arterial supply to this segment, threatening the segment’s viability (see Fig. 45-7F). Documentation of acquired conditions that can compromise arterial inlow (e.g., celiac artery stenosis) can assist the surgeon in planning vascular reconstruction.44,45,75,93,94

Portal Vein Anatomy and Variations A normal portal vein bifurcates at the hilum into right and left main branches (Fig. 45-8A). The right portal vein (RPV) bifurcates into the anterior and posterior branches, which in turn bifurcate into ascending and descending branches, each supplying a segment of the right lobe. The left portal vein (LPV) divides into three branches, each supplying a segment of the left lobe. Variations in portal vein anatomy are seen in approximately 10% to 20% of patients. Variations in the RPV branching pattern are more common. An early bifurcation of the RPV and trifurcation of the main portal vein (MPV) into anterior and posterior divisions and the LPV are the most common variations (see Fig. 45-8B). The anterior division of the RPV may arise from the LPV,

and its origin may be intraparenchymal or extraparenchymal. An undivided MPV with all segmental branches arising directly from the MPV is a rare anatomic variation. Intraparenchymal origin of the anterior division of the RPV from the LPV and undivided MPV variants are absolute contraindications for right lobe donation. Trifurcation of the MPV and extraparenchymal branching of the anterior division of the RPV from the LPV may require surgical reconstruction of two venous anastomoses.20,23,45,66

Hepatic Vein Anatomy and Variations Normal hepatic vein anatomy consists of three major hepatic veins that drain into the inferior vena cava (IVC). The right hepatic vein (RHV) drains hepatic segments 5 to 8; the middle hepatic vein (MHV) drains segments 4, 5, and 8; and the left hepatic vein (LHV) drains segments 2 and 3. A common variation seen in nearly 60% of patients is a common opening of the MHV and LHV into the IVC (Fig. 45-9A). Variations in hepatic vein anatomy that are signiicant for both donor and recipient are seen in approximately 30% of patients. These variations challenge the operating surgeon to modify the hepatectomy plane to avoid excessive bleeding and preserve venous drainage in the donor as well as the recipient. The MHV is an important surgical landmark for the hepatectomy plane in both right lobe and left lateral segment grafts. Early bifurcation of the MHV and large branches draining into the MHV from adjacent segments of the right lobe may require alteration of the hepatectomy plane. Identiication of accessory hepatic veins is essential because they may traverse the hepatectomy plane and cause signiicant hemorrhage and graft ischemia. All accessory hepatic veins larger than 5 mm have to be identiied because they require reimplantation to avoid graft congestion and rejection. An accessory right inferior hepatic vein that drains the posterior segments (6 and 7) of the right lobe is an important variant that should be identiied, and its distance from the main RHV should be measured (see Fig. 45-9B and C). If these two veins are separated by more than 4 cm, it may be dificult to implant both veins with a single partially occluding clamp on the recipient’s IVC. A left lobe venous variant that may alter the surgical approach is an accessory LHV that drains directly into the IVC or MHV.20,45,58,89

Intrahepatic Biliary Duct Anatomy and Variations The right hepatic duct is formed by the conluence of the right posterior duct draining segments 6 and 7 and the right anterior duct draining segments 5 and 8. The left hepatic duct is formed by the segmental branches draining segments 2 to 4. The right hepatic duct, which is shorter, joins the left hepatic duct to form the common hepatic duct

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E

F FIG 45-7 Arterial variations in a liver donor. A, Replaced right hepatic artery (RHA) (arrowhead) arising from the superior mesenteric artery (SMA) (arrow). B, Hepatic artery (white arrow), splenic artery (white arrowhead), and SMA (black arrowhead) arising from a common trunk (black arrow). C and D, Replaced left hepatic artery (LHA) (arrowhead) arising from the left gastric artery (curved arrow) and the RHA (arrow) arising from the celiac trunk. E, Accessory LHA (curved arrow) arising from the left gastric artery, with a normal LHA (arrowhead) and RHA (arrow). F, Artery to segment 4 (curved arrow) arising from the RHA (arrowhead); the LHA is shown (arrow).

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SURGICAL TECHNIQUES Cadaver Liver Transplantation

A

B FIG 45-8 Portal vein in the donor liver. A, Normal main portal vein (arrow) with right and left portal vein branches (arrowheads). B, Trifurcation of the main portal vein (arrow).

(CHD). The cystic duct joins the CHD distal to the conluence of right and left hepatic ducts. This normal biliary anatomy is present in about 58% of the population (Fig. 45-10A).77,109 The most common variant of biliary anatomy, seen in about 13% to 19% of the population, is drainage of the right posterior duct into the left hepatic duct (see Fig. 45-10B).38 Another common variant, seen in about 11% of the population, is the triple conluence of the right anterior duct, right posterior duct, and left hepatic duct to form the CHD.109 A less common variation, seen in about 5% of the population, is direct drainage of the right posterior duct into the CHD or common bile duct (CBD).38,109 Accessory hepatic ducts are present in approximately 2% of the population.24,109 Common cystic duct variations are low insertion of the cystic duct into the distal third of the extrahepatic bile duct in 9%, medial insertion of the cystic duct into the left side of the CHD in 10% to 17%, and a parallel course of the cystic duct and CHD.109,134 Uncommon cystic duct variations include a more proximal opening of the cystic duct into the CHD, aberrant opening of the cystic duct into either the left or right hepatic ducts, and drainage of an aberrant or accessory posterior duct into the cystic duct.50 The presence of these bile duct variations is not an absolute contraindication for transplantation, but preoperative knowledge of them helps the surgeon make appropriate alterations in the resection plane during graft retrieval and ductal anastomosis to avoid potential complications, including bile leaks and strictures.

The surgical technique for cadaver liver transplantation is well established, with minor individual and institutional differences. The basic surgical steps consist of the hepatectomy phase, anhepatic phase with engraftment (with or without venovenous bypass), reperfusion with arterialization, and biliary reconstruction.84,115,129 The vascular anastomosis proceeds in the following order: suprahepatic vena cava, infrahepatic vena cava, portal vein, hepatic artery. The hepatic artery is reconstructed by anastomosis between the donor celiac axis and the recipient hepatic artery bifurcation or the branch point of the gastroduodenal and proper hepatic arteries (Fig. 45-11A and B). The technique of arterial anastomosis depends on the presence of anatomic variations. If the recipient hepatic artery is inadequate, donor iliac artery graft is used to anastomose the hepatic artery to the aorta (see Fig. 45-11C). The donor and recipient portal veins are connected via an end-to-end anastomosis (Fig. 45-12). In recipients with an inadequate portal vein owing to either thrombosis or previous surgery, a venous jump graft from the donor portal vein or iliac vein is used. There are different techniques of IVC anastomosis. The conventional method includes resection of the retrohepatic segment of the recipient IVC and an end-to-end anastomosis of the donor IVC to the suprahepatic and infrahepatic ends of the recipient IVC (Fig. 45-13A to C). This technique may require a temporary venovenous bypass in the recipient between the iliac veins and superior vena cava through the axillary vein. A new technique (piggyback) involves preserving the recipient retrohepatic IVC and creating an anastomosis between the donor IVC and a common stump of the recipient hepatic veins (see Fig. 45-13D). The piggyback technique requires greater surgical skill but has several advantages: avoidance of venovenous bypass, less bleeding, and less chance of adrenal or renal vein injury.111 After the vascular anastomosis, the biliary anastomosis is performed between the donor CBD and the recipient CHD after a cholecystectomy (Fig. 45-14A and B). The choledochocholedochostomy (CDC) can be performed in endto-end or side-to-side fashion. If the recipient duct is diseased or inadequate, a Roux-en-Y hepaticojejunostomy or choledochojejunostomy is performed (see Fig. 45-14C).10,84,115 The CDC technique is preferable because it provides physiologic bile low to the duodenum with preservation of the sphincter of Oddi function, avoids intestinal contamination of the bile ducts, and allows endoscopic diagnostics and interventions.

Living-Donor Liver Transplantation LDLT is more technically challenging than whole cadaver liver transplantation. LDLT initially consisted of left lateral segment liver grafts from an adult donor to a pediatric recipient. The success of these procedures led to the use of right lobe grafts from living donors to adult recipients.133 There are four types of LDLT—left lateral segment graft, left lobe graft, right lobe graft, and extended right lobe graft— depending on the age and size of the recipient, the original disease and clinical status of the recipient, and the quality of the donor liver. The graft size is the major limiting factor in the outcome of LDLT. A minimum graft-to-recipient weight ratio of 0.8% is suficient to meet metabolic demands after transplantation.8,100 The left lateral segment graft (segments 2 and 3) is used for small pediatric recipients, and a left lobe graft (segments 2 to 4) is used for larger children. The line of parenchymal transection is to the right of the falciform ligament in lateral segment grafts and 1 to 2 cm to the right of Cantlie’s line in left lobe grafts (Fig. 45-15A). Cantlie’s line runs from the gallbladder fossa to the IVC. Intraoperative ultrasonography (US) is useful to identify the MHV in the left lobe graft resection. A long length of the LHV is

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C FIG 45-9 Hepatic vein variations in the donor liver. A, Contrast-enhanced axial MRI showing conluence (arrows) of the middle and left hepatic veins and IVC (arrowhead). B and C, Coronal images show the right hepatic vein (arrow) and accessory inferior hepatic vein (arrowhead).

preserved for anastomosis with a common stump of the LHV and MHV of the recipient. The graft portal vein is anastomosed with the LPV, portal vein bifurcation, or the MPV of the recipient. For adult recipients, either a right lobe (segments 5 to 8) or extended right lobe (segments 4 to 8) graft is used. The plane of resection is 1 cm to the right of the MHV for right lobe grafts, and the MHV is included in the graft for extended right lobe grafts (see Fig. 45-15B).43 Extended grafts are used when the graft liver is of limited quality owing to steatosis or elderly age of the donor. Assessment of the venous drainage of segment 4 and any variations in MHV anatomy is important in planning the resection plane for right lobe grafts.86 It is also important to assess preoperatively whether the donor will have adequate liver volume left after extended right lobe donation, because the volume of the left lobe lateral segments is variable. This can be assessed with CT volumetry, and 35% of liver volume is considered to be a safe cutoff point for donation.53 This percentage volume of residual liver is increased in aged donors and those with steatosis.76 Fatty livers are more vulnerable to injury by general anesthesia and ischemiareperfusion. Donor livers with steatosis of 20% or more, especially when the residual liver volume is less than 30%, are excluded from right lobe donor hepatectomy.31,69,88

POSTTRANSPLANT COMPLICATIONS Improved surgical techniques and early detection and correction of postoperative complications have signiicantly improved both graft and patient survival rates. According to the UNOS website (unos.org), the 1-, 5-, and 10-year graft survival rates of liver transplant recipients

who were younger than 65 years were 82.1%, 67.8%, and 52.6%, respectively; for recipients 65 years and older they were 77.5%, 59.7%, and 41.2%, respectively. Imaging plays an important role in the timely detection and treatment of complications. Imaging modalities for evaluation of the transplanted liver include US and cross-sectional imaging with either contrast-enhanced CT or MRI. Each of these modalities has advantages and limitations. US is the preferred imaging modality in the immediate postoperative period.27,37 The study can be performed at the patient’s bedside to detect perihepatic luid collections, biliary dilatation, and vascular low to the liver. Color-low Doppler, with evaluation of the spectral waveform, provides baseline information about the perfusion of the transplanted liver. Although US is useful, it has several limitations. There is a limited imaging window available in the immediate postoperative period owing to extensive bowel gas, pneumoperitoneum, and perihepatic luid collections. Doppler evaluation is also dificult owing to the patient’s inability to cooperate with breath holding. The hepatic arterial anastomosis site is technically dificult to evaluate, and the status of the arterial anastomosis is based on the spectral waveform and resistive index of the downstream arterial low. Contrast-enhanced multidetector CT (MDCT) in the hepatic arterial phase and portal venous phase is ideal for evaluating the transplanted liver. In addition to arterial and venous anatomy, hepatic parenchymal enhancement and perihepatic hematomas and other luid collections are well delineated.65 However, biliary anatomy and complications are not well evaluated by contrast-enhanced CT. Magnetic resonance cholangiopancreatography (MRCP) and gadolinium (Gd)-enhanced MRI can demonstrate vascular, biliary, and

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Posttransplant Liver Complications BOX 45-3

A

B FIG 45-10 Bile duct variations in the donor liver. A, MRCP demonstrates normal biliary anatomy, including the common bile duct (arrow), common hepatic duct (curved arrow), and cystic duct (arrowhead). B, Crossover anomaly of the right posterior hepatic duct (arrow) draining into the left hepatic duct (arrowhead).

parenchymal complications.101,119 Differentiation of perihepatic hematoma from other postsurgical luid collections is also an advantage of MRI. Conventional angiography and cholangiography are used only for the management of vascular and biliary complications. Although CT and MRI are better modalities for imaging a transplanted liver, duplex sonography remains the primary imaging modality in the immediate postoperative period and during follow-up. CT and MRI are generally used when sonography indings are equivocal or there is a discrepancy between the clinical presentation and the sonographic indings. Post–liver transplant complications are broadly classiied into vascular and nonvascular complications (Box 45-3).

Vascular Complications Vascular complications are more serious and are related to the hepatic artery, portal vein, and IVC reconstruction. Hepatic artery and portal vein thrombosis is the most important vascular complication, with a potential for graft failure and need for retransplantation.

Vascular Complications Hepatic artery Hepatic artery stenosis Hepatic artery thrombosis Hepatic artery pseudoaneurysm Portal vein Stenosis Thrombosis Inferior vena cava Stenosis Thrombosis Other Arterioportal istula Splenic artery aneurysm and rupture Biliary Complications Bile leak Biliary obstruction Bile duct stricture Anastomotic stricture Nonanastomotic stricture Biliary calculi Cholangitis Extrinsic compression by luid collections Recurrent cholangiocarcinoma Mucocele of the cystic duct remnant Sphincter of Oddi dysfunction Fluid Collections Hematoma Biloma Seroma Abscess Hepatic Parenchymal Complications Ischemia and infarction Abscess secondary to ischemic necrosis and opportunistic infections Adrenal Hemorrhage Malignancies Posttransplant lymphoproliferative disease Recurrent hepatocellular carcinoma Recurrent cholangiocarcinoma Skin cancer, Kaposi’s sarcoma Other malignancies (e.g., upper airway, lung, gastrointestinal, cervical cancer) Extrahepatic Opportunistic Infections Cytomegalovirus Tuberculosis Aspergillus Pneumocystis jiroveci infection

Hepatic Artery Complications. Hepatic artery complications include thrombosis, stenosis, and pseudoaneurysm formation. Stenosis and thrombosis. Stenosis and thrombosis are interrelated, with hepatic artery stenosis generally leading to thrombosis. Early hepatic artery thrombosis develops within the irst 2 weeks after surgery. Delayed hepatic artery thrombosis develops several years after transplantation as a sequela of chronic rejection and sepsis. Hepatic artery thrombosis occurs more frequently in children (40%) than in adults (4%-12%).39,61 The clinical presentation of hepatic artery

A

B

FIG 45-11 Normal arterial anastomosis in a transplanted liver. Coronal (A) and coronal oblique (B) arterial-phase CT images demonstrate hepatic artery anastomosis between the recipient and donor common hepatic arteries (arrow) and right and left hepatic artery branches (arrowheads) of the transplanted liver. Coronal Gd-enhanced MR angiography (C) demonstrates hepatic artery anastomosis to the infrarenal aorta through an arterial conduit (arrow).

C

ANAS

A

B

FIG 45-12 Normal portal vein anastomosis in a transplanted liver.

C

US with Doppler (A), coronal reconstructed CT (B), and contrastenhanced coronal MRI (C) demonstrate normal portal vein anastomosis (arrow).

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ANAS

ANAS

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B

C

D FIG 45-13 Normal IVC anastomosis in a transplanted liver. Color-low Doppler (A), spectral Doppler (B), and coronal post-Gd MRI (C) demonstrate a conventional end-to-end IVC anastomosis (arrows). In a line diagram (D) showing the piggyback technique of IVC anastomosis, the preserved recipient retrohepatic IVC (straight black arrows), ligated donor IVC (curved black arrows), ligated recipient right hepatic vein (arrowhead), and vascular cuff of the recipient middle and left hepatic veins (red arrows) are anastomosed to the donor IVC.

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A

C FIG 45-14 Bile duct anastomosis. Line diagram (A) and corresponding MRCP image (B) of a transplanted liver with choledochocholedochostomy (arrow in B). Line diagram (C) of choledochojejunostomy (black arrow). The portal vein anastomosis (curved arrow), hepatic artery anastomosis (red arrow), and T-tube (arrowhead) are illustrated in the line diagrams.

thrombosis can vary from catastrophic fulminant hepatic failure to a totally silent event. Other presentations include biliary obstruction, bile leak, or sepsis. Biliary complications result from ischemic necrosis of the bile ducts, which are entirely dependent on hepatic arterial supply, and manifest a few days to weeks after transplantation. Several anatomic or hemodynamic factors can increase the risk for thrombosis. Anatomic factors include signiicant size discrepancy between the donor and recipient arteries, internal laps, prolonged clamping of the artery, kinking of a long artery, prolonged cold ischemia, ABO blood type incompatibility, and rejection.97 Hemodynamic factors include hypercoagulable state in the irst postoperative week and graft edema from hepatic failure and celiac artery stenosis. Other

predisposing factors include interpositional conduit, technical errors, acute rejection, and cytomegalovirus infection. Because the nature of the arterial reconstruction has an effect on the prevalence of arterial thrombosis, an illustration of the type of vascular anastomosis should be provided to the radiologist by the operating surgeon.66,151 In all posttransplant patients with elevated hepatic enzymes and unexplained bacteremia, hepatic artery thrombosis should be excluded by imaging. Because thrombosis occurs at the anastomosis, US is insensitive in demonstrating the actual site of thrombosis, and the diagnosis is based on Doppler low changes in the distal intrahepatic branches. Absence of low in the proper hepatic artery at the porta hepatis and intrahepatic branches is diagnostic of complete hepatic

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B FIG 45-15 Lines of transection in living-donor liver transplantation. Coronal (A) and axial (B) contrastenhanced MRI demonstrates the lines of transection in a left lateral segment graft (yellow line) and a right lobe graft (red line).

artery thrombosis. A tardus parvus pattern of low can be identiied in the intrahepatic branches distal to partial thrombosis or signiicant stenosis (>50%) and in complete occlusion with collateral vessel formation. The tardus parvus low is characterized by low systolic velocity with a resistive index of less than 0.5 and an increased acceleration time of greater than 0.08 second (Figs. 45-16A and 45-17A). A peak systolic velocity of more than 200 cm/sec at the anastomosis is diagnostic of signiicant stenosis. There is wide variation in the reported success rates of Doppler sonography in detecting hepatic artery stenosis. The reported sensitivity and speciicity vary from 91% to 97% and 64% to 99%, respectively.10,28,56,107,140,150 A false-positive sonographic inding of hepatic artery thrombosis is seen with postsurgical edema, systemic hypotension, and high-grade hepatic artery stenosis. Development of periportal arterial collaterals in chronic hepatic artery thrombosis may result in false-negative Doppler indings. In all patients with equivocal sonographic indings, contrastenhanced CT or MRI is invaluable for the diagnosis of hepatic artery thrombosis (see Figs. 45-16B and 45-17B).14,66,67 As a diagnostic criterion for hepatic artery thrombosis, an abrupt cutoff of the hepatic artery at the anastomosis, with nonvisualization of the intrahepatic branches, has a low sensitivity (57%) and high speciicity (99%). Using focal narrowing at the anastomosis as a diagnostic criterion, a sensitivity of 100% and speciicity of 74% are possible. There is often overestimation of stenosis severity with MRI owing to postsurgical changes, susceptibility artifacts from surgical clips, and low-low states.62 Lowlow states result from systemic hypotension or regional causes such as increased resistance to hepatic low from edematous liver or decreased hepatic blood volume due to splenic artery steal phenomenon. These low-low states cause decreased enhancement of intrahepatic arteries. Treatment of hepatic artery thrombosis depends on the timing after transplantation. Acute thrombectomy and revision of the anastomosis within the irst 2 weeks have a success rate of about 50%, and most patients eventually require retransplantation. Management of hepatic artery thrombosis with interventional radiology includes intraarterial thrombolysis with urokinase.63,70,149,163 Hepatic artery stenosis of the anastomosis is managed with either balloon dilation or stent placement.68,114 These measures are palliative and provide a bridge for retransplantation. Hepatic artery pseudoaneurysm. Hepatic artery pseudoaneurysm is an uncommon complication and can be extrahepatic or intra-

hepatic. Extrahepatic pseudoaneurysms develop at the anastomosis, and intrahepatic pseudoaneurysms are a sequela of prior intervention, such as biopsy or biliary intervention, and sepsis. These pseudoaneurysms may be asymptomatic, detected incidentally on imaging, but they are a potential source of rupture and fatal hemorrhage. Rupture of an intrahepatic pseudoaneurysm can lead to a istulous communication with an adjacent portal vein or bile duct. Patients with arteriobiliary istula present with hemobilia and upper gastrointestinal bleeding.81,87 The diagnosis can be made by contrast-enhanced CT or MRI, which shows an enhancing cystic lesion in relation to the artery10,14,64,97 (Fig. 45-18). US demonstrates a periportal or intrahepatic cystic structure with arterial low on color and spectral Doppler analysis.142,156 All intrahepatic and perihepatic cystic structures should be evaluated with Doppler to exclude a pseudoaneurysm. The management options for extrahepatic pseudoaneurysm at the anastomosis are surgical excision and anastomosis, embolization, and exclusion by stent placement. Intrahepatic pseudoaneurysm can be successfully managed with endovascular coil embolization.5,30

Portal Vein Complications. Portal vein thrombosis and stenosis at the anastomosis are uncommon complications reported in 1% to 3% of patients.62,97 These complications can develop in the immediate postoperative period or several months to years after transplantation and manifest clinically with symptoms of portal hypertension, massive ascites, edema, and hepatic failure.97 Factors predisposing to portal vein thrombosis are faulty surgical technique, vessel misalignment, differences in the caliber of donor and recipient veins, previous portal vein surgery, previous portal vein thrombosis in the recipient portal vein system, and hypercoagulable states.143,157 US demonstrates complete occlusion, illing defects, and narrowing of the portal vein (Fig. 45-19A). Mild narrowing at the anastomosis is natural; signiicant stenosis is diagnosed when the peak velocity exceeds 200 cm/sec and the mean anastomotic-to-preanastomotic velocity ratio is greater than 3 : 1 (see Fig. 45-19B).25,74,128 A decrease in the hepatic artery resistive index to less than 0.5 is a secondary sign of portal vein thrombosis.106 CT and MRI demonstrate portal vein thrombosis as illing defects with narrowing of the lumen, and the extent of thrombosis and stenosis is well delineated (Fig. 45-20A; also see Fig. 45-19C). More than 50% narrowing of the portal vein has 100% sensitivity and 84% speciicity in the diagnosis of portal vein

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A

B FIG 45-17 Hepatic artery thrombosis. A, Color-low Doppler US shows

B FIG 45-16 Hepatic artery stenosis. A, Color-low Doppler US of a transplanted liver shows low-resistance arterial low in the liver, with a resistive index of less than 0.5. B, Coronal Gd-enhanced MRI demonstrates focal high-grade stenosis at the hepatic artery anastomosis (arrow), with poststenotic dilatation (arrowhead).

stenosis. The extent and severity of the portosystemic collateral vessels from portal hypertension due to signiicant portal vein stenosis are well delineated with both CT and MRI (see Fig. 45-20B).10,39,61 Percutaneous transhepatic portography can be performed when there is a discrepancy between noninvasive imaging indings and the clinical presentation. This allows measurement of a pressure gradient across the stenosis, with values higher than 5 mm being signiicant.105 Treatment options include surgical thrombectomy, creation of a venous jump graft, portosystemic shunt, and percutaneous transluminal angioplasty with or without stent placement. Patients refractory to these treatments require retransplantation.

Inferior Vena Cava Thrombosis and Stenosis. IVC complications following liver transplantation are uncommon, with a prevalence of less than 1%.39 In a standard technique with suprahepatic and infrahepatic IVC anastomosis, stenosis can occur at either anastomosis. Suprahepatic IVC stenosis presents with clinical features of Budd-

low-resistance arterial low in the liver, with a resistive index of 0.43. B, Coronal Gd-enhanced 3D MR angiogram demonstrates segmental narrowing (arrow) of the hepatic artery at the anastomosis.

Chiari syndrome, including hepatic venous congestion, ascites, decreased renal function, and peripheral edema. Infrahepatic stenosis presents with lower limb edema and decreased renal function without hepatomegaly or ascites. Secondary thrombosis of the IVC and hepatic veins can develop following suprahepatic IVC stenosis. In the piggyback technique, the recipient IVC is retained with an end-to-side anastomosis of the common cuff of the donor hepatic vein and the recipient IVC. Less commonly, stenosis can occur at this end-to-side anastomosis.95,102 Stenosis at the anastomosis can result from faulty surgical technique, swelling of the transplanted liver, kinking of the suprahepatic IVC from rotation of the liver, and discrepancy between the donor and recipient IVCs. In the case of IVC thrombosis, US may demonstrate IVC narrowing and echogenic intraluminal thrombus. Doppler evaluation at the anastomosis demonstrates a threefold increase in velocity compared with that in the prestenotic segment and monophasic low in the IVC and hepatic veins proximal to the stenosis.25,112 The severity and extent of stenosis and thrombosis are well demonstrated on coronal and sagittal reconstructed CT and MRI10,39,61 (Figs. 45-21A and 45-22). IVC stenosis can be treated initially with percutaneous transluminal angioplasty and with stent placement if angioplasty is unsuccessful (see Fig. 45-21C).12,147,161

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Liver Transplantation

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D

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F

E FIG 45-18 Hepatic artery pseudoaneurysm and arteriobiliary istula. This patient with a transplanted liver presented with upper gastrointestinal bleeding following a left hepatic lobe biopsy. Ultrasonography (A) and contrast-enhanced CT (B) show intrahepatic biliary dilatation (arrows). ERCP (C) demonstrates a dilated left hepatic duct with a illing defect (arrow). Selective hepatic angiogram in the arterial phase (D) demonstrates a small pseudoaneurysm (arrow) in relation to a peripheral branch of the left hepatic artery; a subsequent image (E) shows contrast illing of a dilated left hepatic bile duct (arrows) and the left hepatic artery (curved arrow), indicating an arteriobiliary istula. The patient was successfully treated with coil embolization (arrow in F) of the left hepatic artery branch.

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C FIG 45-19 Portal vein stenosis. This liver transplant patient presented with recurrent portal hypertension. Color-low (A) and spectral (B) Doppler US images demonstrate turbulent low with high velocity at the portal vein anastomosis (arrow in A). Coronal reconstructed CT in the portal venous phase (C) demonstrates focal stenosis (arrow) of the main portal vein at the anastomosis.

Other Vascular Complications Splenic artery aneurysm. The incidence of splenic artery aneurysm is higher in patients with cirrhosis and portal hypertension and varies from 7% to 10%. This increased incidence is presumably due to the hyperkinetic state of the spleen in portal hypertension. The risk of splenic artery aneurysm is persistently high after liver transplantation, with a reported prevalence of about 13%. There is also increased risk of rupture of these aneurysms after transplantation, especially if they are larger than 1.5 cm, owing to decreased portal venous low and increased splenic artery low. Therefore any splenic artery aneurysm detected during pretransplant evaluation of a recipient should be resected at the time of transplantation. Posttransplant splenic artery aneurysms tend to be multiple and occur more frequently in the distal third of the splenic artery.14,69,99 Intrahepatic arterioportal fistula. Intrahepatic arterioportal istula is a complication that develops in a transplanted liver following a surgical or percutaneous liver biopsy to exclude graft rejection. The reported incidence of these istulas is 50% in the irst week after the biopsy, and they tend to resolve spontaneously. These istulas are small and are not usually detected by color-low Doppler US. They have a characteristic appearance on contrast-enhanced CT and MRI; they are seen as peripheral portal branch enhancement in the arterial phase, without enhancement of the main portal vein and superior mesenteric vein. With very small arterioportal istulas, there is increased focal, peripheral, wedge-shaped parenchymal enhancement in the arterial phase compared with the rest of the normal hepatic parenchyma; this is referred to as transient hepatic attenuation difference.22

Diffuse periportal hypodensity. Diffuse periportal hypodensity on contrast-enhanced CT and hyperintensity on T2-weighted MRI in a transplanted liver are due to dilated lymphatics from impaired drainage into the extrahepatic lymphatic system (Fig. 45-23). This resolves with the development of alternative pathways of lymphatic drainage, which may take weeks to months. This is not a sign of graft rejection, as once believed, and should not be mistaken for dilated bile ducts.73 Splenic artery steal syndrome. Splenic artery steal syndrome is characterized by arterial hypoperfusion of the transplant liver due to shift of blood low from celiac trunk into splenic artery. It has a reported incidence of 3% to 8% after orthotopic liver transplant. It is thought to be due to hepatic arterial buffer response secondary to increased portal venous low. Its onset may be as early as a few hours after the transplant to several weeks after transplant. Decreased hepatic arterial perfusion of the transplant liver may lead to ischemic biliary disease and graft loss. Doppler US demonstrates decreased peak systolic velocity of intrahepatic arteries with or without corresponding increase in resistivity index (RI). Celiac angiography demonstrates a patent hepatic artery but delayed and reduced contrast illing of the hepatic artery and its branches as compared to other branches of celiac trunk. Treatment is by selective arterial embolization of the proximal splenic artery.145

Biliary Complications Biliary complications have been a common cause of morbidity from the early days of orthotopic liver transplantation. The incidence of biliary complications has decreased owing to improved surgical

CHAPTER 45

A

B FIG 45-20 Portal vein thrombosis. A, Coronal Gd-enhanced MRI in the portal venous phase shows thrombosis of the entire main portal vein (arrows), with dilated collaterals in the left upper quadrant (arrowheads). B, Delayed coronal MRI demonstrates dilated splenic collateral veins (arrowheads), with a splenorenal shunt and dilated left renal vein (arrow).

techniques, and the current reported incidence is 10% to 15%.46,104 However, with the wide use of split-liver, reduced-size, and livingdonor transplants, there has been a resurgence of biliary complications. The incidence of biliary complications is higher in LDLT, with multiple biliary reconstructions rather than a single biliary anastomosis. Irrespective of the type of biliary reconstruction, the two most common biliary complications are bile leak and bile stricture.40,52,128 Less common complications include bile duct obstruction from kinking, stone, or sludge; sphincter of Oddi dysfunction; and mucocele of the cystic duct remnant.159

Bile Leak. The reported incidence of bile leak varies from approximately 6% to 10% following orthotopic liver transplantation. The clinical presentation of bile leak is variable and includes excess bile from intraabdominal drains, abdominal pain, elevated serum bilirubin and liver enzymes, and fever. Because the clinical presentation and laboratory indings are nonspeciic, radiographic imaging and intervention play a crucial role in the early diagnosis and management of bile leaks. Types. There are three types of bile leaks: leaks at the T-tube insertion, anastomotic leaks, and nonanastomotic leaks. Bile leak most commonly occurs at the T-tube site after its removal. It can be caused by errors in tube placement or displacement of the tube outside the duct. It is not associated with vascular complications

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and bile duct ischemia. The degree of bile leak varies from a small leak along the T-tube track to a signiicant leak with perihepatic biloma and bilious ascites. There is evidence of an increased incidence of bile leak with T-tube placement, so the new surgical strategy is to avoid T-tube placement after biliary reconstruction.96,98 Anastomotic leaks generally occur in the irst month after transplantation. They are commonly the result of faulty surgical technique, with excessive tension on the biliary anastomosis and dissection around the duct, with ischemia and necrosis. This ischemia is most often due to local periductal dissection and less commonly to hepatic artery thrombosis. Anastomotic leaks can occur at both choledochocholedochostomy and choledochojejunostomy sites, but a much higher incidence is reported with the latter. This is believed to be due to a higher rate of infection and ischemia with choledochojejunostomy. Nonanastomotic leaks are a result of bile duct ischemia and necrosis as a sequela of hepatic artery thrombosis. This type of leak is often associated with infection and graft dysfunction and has a poor prognosis, with most patients requiring retransplantation. Hepatic artery thrombosis has to be excluded in all patients with nonanastomotic leak, because 90% of these leaks are a result of ischemia.10,96,98,121,145,151,160 Imaging techniques. US demonstrates perihepatic luid collections with or without biliary dilation. CT and MRI demonstrate the extent of luid collections but cannot differentiate bile from nonhemorrhagic luid collections (Fig. 45-24A). Because it is not possible to differentiate a bilious collection from other luid collections with US, CT, or MRI, hepatobiliary scintigraphy should be obtained in all patients with suspected bile leak (see Fig. 45-24B). Alternatively, imaging-guided aspiration of the luid collection may be performed to conirm a bile leak. Fluid collections at the anastomotic site should always be considered a possible bile leak, necessitating follow-up imaging. Conventional T2-weighted MRCP demonstrates the relationship of luid collections to intrahepatic and extrahepatic bile ducts but cannot show direct evidence of a bile leak.10,51,59 Three MRI contrast agents that are taken up by functioning hepatocytes and excreted into the bile should be able to provide functional evidence of a bile leak. One such contrast medium is mangafodipir trisodium, not approved by the U.S. Food and Drug Administration (FDA) for regular use. Gadobenate dimeglumine (Gd-BOPTA)/Multihance and gadoxetic acid (Gd-EOB-DTPA)/Eovist are FDA approved for regular use. These are T1-shortening contrast agents, with hyperintense signal intensity of the bile on T1 imaging. The major limitation of Gd-BOPTA (Multihance) is that only 3% to 5% of the contrast agent is excreted into the biliary system and needs delayed imaging at 60 to 90 minutes after contrast administration. In contrast, 50% of gadoxetic acid (Eovist) contrast agent is excreted by the biliary system, and bile ducts are opaciied by 20 minutes delay after contrast administration.3,15,63 Invasive imaging with endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) are undertaken if the patient is being considered for biliary stenting. Management. The management of bile leaks depends on their location and origin. Small leaks at the T-tube insertion resolve spontaneously and are followed with imaging. Large bilomas and bilious ascites need imaging-guided percutaneous drainage because they are a potential source of infection in these immunocompromised patients. Patients with persistent bile leak and anastomotic stricture are initially managed with percutaneous and endoscopic stenting. Surgical correction should be considered only when nonoperative measures fail. Patients with nonanastomotic leaks from hepatic artery thrombosis eventually need retransplantation.52,57 Surgical management of nonanastomotic strictures is dificult because of their multiplicity and intrahepatic nature. Percutaneous nonoperative treatment with balloon dilation and stenting has a major

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FIG 45-21 IVC stenosis. A, Coronal Gd-enhanced MRI of the liver demonstrates stenosis (arrow) at the suprahepatic IVC anastomosis. B, Stenosis (arrow) is conirmed by an inferior venacavogram. C, Inferior venacavogram after balloon dilation of the stenosis (arrow).

role in the management of these strictures. The success rate of these nonoperative methods is variable, with better success in nonischemic strictures. In most cases, patients with nonanastomotic strictures caused by ischemia eventually need retransplantation, and the percutaneous methods are palliative until a suitable donor liver becomes available.118,128,139,151

Biliary Obstruction Biliary stricture. Biliary obstruction due to strictures develops several months to years after transplantation. The actual incidence of biliary stricture varies among different centers, but the reported incidence ranges from 12% to 15%.26,32,121,135 Biliary strictures in a transplanted liver are classiied as anastomotic or nonanastomotic, and distinguishing between the two is relevant because they differ in terms of morphology, pathogenesis, and prognosis. The reported incidence of anastomotic strictures in the literature is around 4% to 9%. The onset of these strictures depends upon the etiology. Early-onset strictures are related to improper surgical

technique, mismatch of the recipient and donor bile duct size, bile leak, and infection.128,151 Later-onset strictures are more related to ibrosis secondary to ischemia. The incidence is higher with right lobe livingdonor transplants than with whole-liver grafts, owing to blood supply at the anastomosis and multiple small-caliber donor ducts. Anastomotic strictures are seen with both choledochocholedochostomy and choledochojejunostomy biliary reconstruction.26,40,42,46,52,96,98,104,121,128 MRCP with three-dimensional (3D) MPR is excellent for the diagnosis of anastomotic strictures. These strictures are seen as abrupt short-segment narrowing of the duct, with proximal biliary dilatation51 (Figs. 45-25 and 45-26). Anastomotic strictures may have clinical and biochemical evidence of cholestasis or can be incidental indings on routine follow-up imaging. Owing to the chronic and indolent nature of these strictures, intraductal calculi, sludge, and cholangitis may be associated. Because anastomotic strictures are generally not associated with other hepatic or vascular complications, they are managed successfully with percutaneous balloon dilation (see Fig. 45-25C and D).26,32,135

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FIG 45-22 IVC thrombosis. A, Coronal MR venogram demonstrates thrombosis of the entire retrohepatic IVC of the transplanted liver (arrows). B, Sagittal MR venogram demonstrates IVC thrombosis (arrows) and dilated ascending lumbar and azygos collateral veins (arrowheads).

FIG 45-23 Periportal hypodensity. Contrast-enhanced CT of a transplanted liver 1 week after the surgery demonstrates diffuse periportal hypodensity (arrowheads) due to dilated lymphatics. This will eventually resolve with the development of new lymphatic pathways.

Nonanastomotic bile duct strictures are multiple and intrahepatic. They are often caused by bile duct ischemia secondary to hepatic artery thrombosis or stenosis. Other causative factors include prolonged cold ischemia, chronic rejection, and cholangitis from opportunistic infections such as cytomegalovirus.18,26,10,151,116,121 Nonanastomotic strictures may also be caused by recurrence of the primary disease in patients

who had liver transplantation for primary sclerosing cholangitis14,41 (Fig. 45-27). These strictures commonly involve the central bile ducts at the hilum, with variable involvement of the right and left intrahepatic ducts. Owing to ischemic necrosis, nonanastomotic strictures are associated with other complications such as leak and biloma with secondary infection and abscess formation. Nonanastomotic strictures present earlier than anastomotic strictures, and clinical presentation is variable and includes jaundice, cholangitis with fever and chills, and increased liver function tests. Imaging with US and CT may demonstrate biliary dilatation, intrahepatic biloma, abscess, and associated vascular thrombosis (Fig. 45-28A). However, MRCP with contrast-enhanced MRI is the best noninvasive imaging method to demonstrate short-segment anastomotic stricture and multiple intrahepatic bile duct nonanastomotic strictures, biliary dilatation, cholangitis (see Fig. 45-25), intrahepatic abscess, and vascular thrombosis (see Fig. 45-28B and C).18,51,62,121,128 ERCP and PTC are invasive and reserved for therapeutic intervention after identiication of strictures by noninvasive imaging with MRCP. Endoscopic or percutaneous balloon dilation with or without stent placement is the irst line of management of anastomotic strictures. Surgical revision and biliary reconstruction with hepaticojejunostomy is indicated when percutaneous or endoscopic treatment fails.10,26,121,128,155 Other causes of biliary obstruction. Biliary cast syndrome is an uncommon complication caused by the diffuse formation of biliary casts, causing biliary obstruction. The incidence is not known, and the timing is variable after transplantation surgery. The exact cause is not known, but it is believed to be multifactorial, including acute cellular rejection, prolonged cold ischemic time, stricture, biliary drainage tubes, stasis, sludge formation, and infection. Ischemia and stricture formation are thought to be common predisposing factors for this syndrome. Noninvasive imaging demonstrates nonspeciic biliary

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F FIG 45-24 Bile leak. A, Contrast-enhanced CT of a patient with a recent liver transplant demonstrates a perihepatic luid collection (arrows). B, Hepatobiliary scan 3 hours after the tracer injection shows increased perihepatic activity (arrows) within the collection, conirming a bile leak. Axial (C) and coronal (D) T2-weighted MRI 48 hours after transplant demonstrates a large perihepatic luid collection (arrow). Coronal (E) and axial (F) T1-weighted image 25 minutes after IV administration of hepatobiliary contrast (Eovist) demonstrates extravasation of biliary contrast (arrow) into the perihepatic collection, conirming bile leak.

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FIG 45-25 Anastomotic stricture of the bile duct. MRCP (A) and ERCP (B) images demonstrate a stricture (arrow) at the choledochocholedochostomy. Balloon dilation (C) and postdilation ERCP image (D) of the stricture (arrow).

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B FIG 45-27 Nonanastomotic biliary strictures from recurrent primary

B

sclerosing cholangitis. A, Coronal MRCP of a transplanted liver shows multiple short segmental strictures of the intrahepatic bile ducts (arrows). B, Gd-enhanced MRI of the liver demonstrates dilated ducts with diffuse mural thickening of the bile ducts (arrows).

FIG 45-26 Anastomotic stricture of the bile duct. MRCP (A) and percutaneous transhepatic cholangiogram (B) of a transplanted liver demonstrate stenosis (arrow) at the biliary-enteric anastomosis.

Fluid Collections dilatation, and a deinitive diagnosis is made with ERCP and PTC. Initial management is by percutaneous or endoscopic cast clearance. Surgery is reserved for those refractory to nonoperative measures.103,120 Less common causes of biliary obstruction in transplanted livers are biliary calculi, sphincter of Oddi dysfunction, and recurrent cholangiocarcinoma. Biliary calculi are identiied as hypointense dependent illing defects on MRCP, differentiating them from hypointense nondependent defects caused by air bubbles from pneumobilia and biliary enteric anastomosis (Fig. 45-29). In patients with sphincter of Oddi dysfunction, there is generalized ductal dilatation beyond the anastomosis up to the ampulla (Fig. 45-30). This papillary dysfunction is presumably due to denervation of the papilla during hepatectomy of the recipient liver.137 Recurrence of cholangiocarcinoma involves the ducts at the anastomosis or the intrahepatic ducts or involves the lymph nodes at the porta hepatis. Mucocele of the cystic duct remnant of an allograft can cause biliary obstruction by extrinsic compression of the CHD. US reveals intrahepatic biliary dilatation and a luid-illed cystic structure at the level of the CHD. A deinitive diagnosis can be made with MRCP or a cholangiogram.1,10,146

Posttransplant perihepatic luid collections are common and are due to hematoma, seroma, biloma, and abscess formation. Postoperative luid collections and hematomas are common at the anastomotic areas in the hilum, adjacent to the IVC, and in the lesser sac and perihepatic and subphrenic spaces. Perihepatic luid collections can be easily identiied and quantiied on postoperative surveillance US. Perihepatic hematomas have a variable sonographic appearance depending on their age. Acute and subacute hematomas have variable echogenicity on US and hyperattenuation on CT and can be readily distinguished from ascites (Fig. 45-31A and B).2,10,29,79 Large perihepatic hematomas in the immediate postoperative period should initiate a search for active hemorrhage and possibly timely surgical reexploration. Bilomas cannot be distinguished from other nonbilious luid collections with any of the noninvasive imaging methods (see Fig. 45-24A). Perihepatic luid collections that increase in size on follow-up imaging and may be caused by a bile leak should be aspirated under imaging guidance to conirm a biloma; the luid should also be cultured because bilomas pose a high risk of infection and subsequent abscess formation. Once a biloma is conirmed, hepatobiliary scintigraphy is necessary to conirm an active bile leak (see Fig. 45-24B). Infected luid collections

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FIG 45-28 Biliary strictures. A, US of a transplanted liver demonstrates intrahepatic bile duct dilatation (arrow). B, MRCP shows an anastomotic stricture (arrowhead) and nonanastomotic strictures (arrows). C, Intraoperative cholangiogram after contrast injection proximal to the anastomosis shows nonanastomotic strictures (arrows).

cannot be distinguished from other luid collections by imaging, and all patients with unexplained fever should have this luid aspirated and analyzed. Large perihepatic luid collections can affect the vascular and biliary anastomosis and eventually survival of the graft. Percutaneous drainage of perihepatic luid collections can be successfully performed with either US or CT guidance.2,17

Adrenal Hemorrhage Right adrenal hemorrhage is a known complication of liver transplantation; it is due to ligation or division of the adrenal vein at the time of hepatectomy of the recipient liver, resulting in adrenal hemorrhage or hemorrhagic infarction. It appears as a hyperechoic mass on US and a hyperdense mass on CT in the right adrenal region adjacent to the IVC (see Fig. 45-31C). MRI demonstrates a hyperintense mass on fatsaturated T1-weighted images.13,108,127 The hemorrhage resolves spontaneously without the development of adrenal insuficiency or other complications. The incidence of adrenal hemorrhage is reported to be lower following piggyback-type IVC reconstruction, because the recipient IVC is retained, making injury to the adrenal vein less likely.

Neoplasms of the Transplanted Liver Recurrence of the primary hepatic malignancy in the resected liver can develop within the transplanted liver. The reported recurrence of HCC in transplanted livers varies widely depending on the pretransplant selection criteria and the underlying primary hepatic disease.56 The original stage of HCC, histologic grade, and vascular invasion are all predictors of tumor recurrence and survival of the recipient. Assessment of the tumor burden by preoperative imaging, with attention to tumor size and multiplicity, is vital for proper patient selection.123,148 Adjuvant chemotherapy and preoperative chemoembolization can reduce the tumor burden while waiting for a donor liver.9,10,141 (Fig. 45-32) The most common site of recurrence is lung, followed by liver (Fig. 45-33) and regional and distant lymph nodes. Recurrence in the lung is due to the embolization of malignant cells before or during surgery and is augmented by immunosuppression.33 Liver transplantation after neoadjuvant chemoradiation is an accepted treatment option for selected patients with perihilar cholangiocarcinoma. Proper patient selection is important because there is a

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FIG 45-30 Papillary dysfunction. MRCP of a transplanted liver demonstrates smooth narrowing of the common bile duct at the ampulla (arrow), with biliary dilatation proximal and distal to the anastomosis (arrowhead).

FIG 45-29 Choledocholithiasis. MRCP of a transplanted liver demonstrates a common bile duct calculus (arrow) distal to the anastomosis (arrowhead).

B A

C FIG 45-31 Perihepatic luid collections. A, Immediate postoperative US of a transplanted liver shows an echogenic perihepatic collection (arrows). B, Corresponding CT shows a hyperdense perihepatic hematoma (arrows). C, Contrast-enhanced CT in another patient demonstrates a perihepatic hematoma (arrows) as well as right adrenal hemorrhage (arrowhead).

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FIG 45-32 Transarterial chemoembolization (TACE) of HCC in pretransplant liver to reduce tumor burden. Pretreatment post-Gd T1-weighted MRI in arterial (A) and portal venous (B) phases demonstrate enhancing mass (arrow) with washout. Post-TACE T1-weighted MRI in arterial (C) and portal venous (D) phases demonstrate no enhancement of the mass (arrow).

higher rate of recurrence in the transplanted liver in elderly patients with large primary tumors and high CA19-9 levels.47,48 Liver transplant recipients are also at a higher risk than the general population for malignancy unrelated to the original hepatic malignancy. Prolonged immunosuppression is the leading cause of this increased incidence of de novo malignancy, although other factors such as chronic viral infections, the patient’s age, alcohol use, and smoking play an important role.19,136 Skin cancer and lymphoproliferative disease are the most common malignancies in liver transplant recipients. Squamous cell carcinoma and Kaposi’s sarcoma are the most common types of skin cancer, though an increased incidence of basal cell and Merkel cell carcinomas has been reported.36 Posttransplant lymphoproliferative disease has an established association with the degree of immunosuppression and Epstein-Barr virus infection. B-cell lymphoma is the most common form; it has a predilection for extranodal involvement and develops within 1 year of transplantation

(Fig. 45-34). Extranodal sites include the liver, spleen, gastrointestinal tract, kidneys, and adrenals.82 Hepatic involvement can be intraparenchymal or hilar in location. The hilar type is more common, with hypodense masses encasing the hilar vessels and ducts. The hepatic parenchymal type presents as hypoechoic mass lesions on US and hypodense mass lesions on contrast-enhanced CT.37,97,131 Malignancies of the upper airways, lungs, and gastrointestinal tract are also reported to occur in liver transplant recipients.55 Patients with primary sclerosing cholangitis as the primary disease are at risk of developing colon cancer owing to its association with inlammatory bowel disease.11

Nonneoplastic Hepatic Parenchymal Complications Hepatic parenchymal ischemia and infarction are uncommon in a normal liver owing to hepatic arterial and portal vascularity and an abundant collateral supply. In a transplanted liver, infarction can occur following hepatic artery or portal vein thrombosis but is more frequent

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FIG 45-33 Recurrent HCC in transplant liver. A, Axial T2-weighted MRI demonstrates a well-deined T2-hyperintense mass lesion in segment 8. Axial post-Gd T1-weighted MRI in arterial dominant phase (B) and portal venous phase (C) demonstrates enhancement in arterial dominant phase and washout in portal venous phase.

A

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C FIG 45-34 Posttransplant lymphoma. Axial (A) and coronal (B and C) Gd-enhanced MRI of the abdomen and pelvis demonstrates large, enhancing, mesenteric mass lesions (arrows). CT-guided biopsy and histopathology of these lesions conirmed B-cell lymphoma.

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Epstein-Barr virus, Pneumocystis jiroveci, Aspergillus spp., and Nocardia spp. Prevention, early detection, and timely management of these infections are vital to decrease morbidity and mortality. Imaging is complementary to clinical and laboratory tests for early detection of these infections.6,124

CONCLUSION

1 2

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Liver transplantation is an established technique for the management of patients with chronic liver disease. The addition of new indications for liver transplantation has further increased the number of patients waiting for liver transplants. As a result, new surgical techniques such as LDLT have been devised. This development has increased the responsibility of the radiologist from detecting postoperative complications to performing preoperative evaluations for the selection of both recipients and donors. Advances in imaging techniques and the feasibility of multimodality imaging of the liver have placed the radiologist at the forefront of liver transplantation. The radiologist must be familiar with new surgical techniques to enable a better understanding of the surgical anatomy and postoperative complications. The radiologist is now a key member of the transplant team.

REFERENCES

B FIG 45-35 Liver abscess. This patient with a liver transplant presented with fever and elevated white cell count. A, US demonstrates a large cystic mass in the left lobe of the liver. B, Contrast-enhanced CT demonstrates a cystic mass with an enhancing wall (arrow). The diagnosis was conirmed by CT-guided drainage of the abscess.

with the former. It is caused by disruption of the collateral vascular supply to the liver during transplantation surgery. Hepatic infarcts are seen as peripheral wedge-shaped low-attenuation areas on contrastenhanced CT or hypointense areas on MRI. The infarcted parenchyma undergoes liquefactive necrosis and is prone to infection and abscess formation10,29,37,39 (Fig. 45-35). Rejection of a liver transplant is diagnosed by biopsy and histopathology. The role of imaging in rejection is to exclude other vascular and nonvascular hepatic complications.97

Extrahepatic Opportunistic Infections Infection continues to be a major cause of morbidity and mortality in liver transplant patients. Apart from infections related to postsurgical complications, these patients are prone to extrahepatic infections owing to their immunosuppressed state. Extrahepatic sites of infection include the skin, upper airways, lungs, gastrointestinal tract, urinary tract, and central nervous system. These infections can be caused by community-acquired or hospital-based infectious agents. Common opportunistic infectious agents are cytomegalovirus,

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cholangiography study with analyses of predictive factors. Liver Transpl 11:1361–1369, 2005. Bridges MD, May GR, Harnois DM: Diagnosing biliary complications of orthotopic liver transplantation with mangafodipir trisodiumenhanced MR cholangiography: Comparison with conventional MR cholangiography. AJR Am J Roentgenol 182:1497–1504, 2004. Brown RS, Jr, Kumar KS, Russo MW, et al: Model for end-stage liver disease and Child-Turcotte-Pugh score as predictors of pretransplantation disease severity, posttransplantation outcome, and resource utilization in United Network for Organ Sharing status 2A patients. Liver Transpl 8:278–284, 2002. Campatelli A, Di Candio G, Morelli L, et al: Interventional ultrasound: Experience in 426 orthotopic liver transplantations. Transplant Proc 36:550–551, 2004. Campbell WL, Sheng R, Zajko AB, et al: Intrahepatic biliary strictures after liver transplantation. Radiology 191:735–740, 1994. Romero-Vargas ME, Flores-Cortes M, Valera Z, et al: Cancers of new appearance in liver transplant recipients: Incidence and evolution. Transplant Proc 38:2508–2510, 2006. Carr JC, Nemcek AA, Jr, Abecassis M, et al: Preoperative evaluation of the entire hepatic vasculature in living liver donors with use of contrast-enhanced MR angiography and true fast imaging with steady-state precession. J Vasc Interv Radiol 14:441–449, 2003. Chaib E, Ribeiro MA, Jr, Saad WA, et al: The main hepatic anatomic variations for the purpose of split-liver transplantation. Transplant Proc 37:1063–1066, 2005. Chen WP, Chen JH, Hwang JI, et al: Spectrum of transient hepatic attenuation differences in biphasic helical CT. AJR Am J Roentgenol 172:419–424, 1999. Cheng YF, Huang TL, Lee TY, et al: Variation of the intrahepatic portal vein; angiographic demonstration and application in living-related hepatic transplantation. Transplant Proc 28:1667–1668, 1996. Choi JW, Kim TK, Kim KW, et al: Anatomic variation in intrahepatic bile ducts: An analysis of intraoperative cholangiograms in 300 consecutive donors for living donor liver transplantation. Korean J Radiol 4:85–90, 2003. Chok KS1, Lo CM: Prevention and management of biliary anastomotic stricture in right-lobe living-donor liver transplantation. J Gastroenterol Hepatol 29(10):1756–1763, 2014. Chong WK, Beland JC, Weeks SM: Sonographic evaluation of venous obstruction in liver transplants. AJR Am J Roentgenol 188:W515–W521, 2007. Colonna JO, 2nd, Shaked A, Gomes AS, et al: Biliary strictures complicating liver transplantation: Incidence, pathogenesis, management, and outcome. Ann Surg 216:344–350, 1992. Crossin JD, Muradali D, Wilson SR: US of liver transplants: Normal and abnormal. Radiographics 23:1093–1114, 2003. Dodd GD, 3rd, Memel DS, Zajko AB, et al: Hepatic artery stenosis and thrombosis in transplant recipients: Doppler diagnosis with resistive index and systolic acceleration time. Radiology 192:657–661, 1994. Dupuy D, Costello P, Lewis D, et al: Abdominal CT indings after liver transplantation in 66 patients. AJR Am J Roentgenol 156:1167–1170, 1991. Elias G, Rastellini C, Nsier H, et al: Successful long-term repair of hepatic artery pseudoaneurysm following liver transplantation with primary stent-grafting. Liver Transpl 13:1346–1348, 2007. Escartin A, Sapisochin G, Bilbao I, et al: Recurrence of hepatocellular carcinoma after liver transplantation. Transplant Proc 39:2308–2310, 2007. Fan ST, Lo CM, Liu CL, et al: Safety of donors in live donor liver transplantation using right lobe grafts. Arch Surg 135:336–340, 2000. Feller RB, Waugh RC, Selby WS, et al: Biliary strictures after liver transplantation: Clinical picture, correlates and outcomes. J Gastroenterol Hepatol 11:21–25, 1996. Ferris JV, Baron RL, Marsh JW, Jr, et al: Recurrent hepatocellular carcinoma after liver transplantation: Spectrum of CT indings and recurrence patterns. Radiology 198:233–238, 1996.

37. Forman LM, Lucey MR: Predicting the prognosis of chronic liver disease: An evolution from child to MELD. Mayo end-stage liver disease. Hepatology 33:473–475, 2001. 38. Freeman RB, Jr: Transplantation for hepatocellular carcinoma: The Milan criteria and beyond. Liver Transpl 12(Suppl 2):S8–S13, 2006. 39. Fung JJ, Jain A, Kwak EJ, et al: De novo malignancies after liver transplantation: A major cause of late death. Liver Transpl 7(Suppl 1):S109–S118, 2001. 40. García-Criado A, Gilabert R, Bargalló X, et al: Radiology in liver transplantation. Semin Ultrasound CT MR 23:114–129, 2002. 41. Gazelle GS, Lee MJ, Mueller PR: Cholangiographic segmental anatomy of the liver. Radiographics 14:1005–1013, 1994.39. 42. Gondolesi GE, Varotti G, Florman SS, et al: Biliary complications in 96 consecutive right lobe living donor transplant recipients. Transplantation 77:1842–1848, 2004. 43. Graziadei IW: Recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl 8:575–581, 2002. 44. Graziadei IW, Sandmueller H, Waldenberger P, et al: Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl 9:557–563, 2003. 45. Graziadei IW, Schwaighofer H, Koch R, et al: Long-term outcome of endoscopic treatment of biliary strictures after liver transplantation. Liver Transpl 12:718–725, 2006. 46. Greif F, Bronsther OL, Van Thiel DH, et al: The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 219:40–45, 1994. 47. Grewal HP, Shokouh-Amiri MH, Vera S, et al: Surgical technique for right lobe adult living donor liver transplantation without venovenous bypass or portocaval shunting and with duct-to-duct biliary reconstruction. Ann Surg 233:502–508, 2001. 48. Gruttadauria S, Foglieni CS, Doria C, et al: The hepatic artery in liver transplantation and surgery: Vascular anomalies in 701 cases. Clin Transplant 15:359–363, 2001. 49. Guiney MJ, Kruskal JB, Sosna J, et al: Multi-detector row CT of relevant vascular anatomy of the surgical plane in split-liver transplantation. Radiology 229:401–407, 2003. 50. Hampe T, Dogan A, Encke J, et al: Biliary complications after liver transplantation. Clin Transplant 20(Suppl 17):93–96, 2006. 51. Heimbach JK, Gores GJ, Haddock MG, et al: Liver transplantation for unresectable perihilar cholangiocarcinoma. Semin Liver Dis 24:201–207, 2004. 52. Heimbach JK, Gores GJ, Haddock MG, et al: Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation 82:1703–1707, 2006. 53. Hertl M, Cosimi AB: Liver transplantation for malignancy. Oncologist 10:269–281, 2005. 54. Hirao K, Miyazaki A, Fujimoto T, et al: Evaluation of aberrant bile ducts before laparoscopic cholecystectomy: Helical CT cholangiography versus MR cholangiography. AJR Am J Roentgenol 175:713–720, 2000. 55. Hoeffel C, Azizi L, Lewin M, et al: Normal and pathologic features of the postoperative biliary tract at 3D MR cholangiopancreatography and MR imaging. Radiographics 26:1603–1620, 2006. 56. Horrow MM, Blumenthal BM, Reich DJ, et al: Sonographic diagnosis and outcome of hepatic artery thrombosis after orthotopic liver transplantation in adults. AJR Am J Roentgenol 189(2):346–351, 2007. 57. Hwang S, Lee SG, Sung KB, et al: Long-term incidence, risk factors, and management of biliary complications after adult living donor liver transplantation. Liver Transpl 12:831–838, 2006. 58. Ito T, Kiuchi T, Egawa H, et al: Surgery-related morbidity in living donors of right-lobe liver graft: Lessons from the irst 200 cases. Transplantation 76:158–163, 2003. 59. Iwasaki M, Takada Y, Hayashi M, et al: Noninvasive evaluation of graft steatosis in living donor liver transplantation. Transplantation 78:1501–1505, 2004.

CHAPTER 45 60. Jimenez C, Marques E, Loinaz C, et al: Upper aerodigestive tract and lung tumors after liver transplantation. Transplant Proc 35:1900–1901, 2003. 61. Johnston TD, Gates R, Reddy KS, et al: Nonoperative management of bile leaks following liver transplantation. Clin Transplant 14:365–369, 2000. 62. Kamel IR, Lawler LP, Fishman EK: Variations in anatomy of the middle hepatic vein and their impact on formal right hepatectomy. Abdom Imaging 28:668–674, 2003. 63. Kantarcı M, Pirimoglu B, Karabulut N, et al: Non-invasive detection of biliary leaks using Gd-EOB-DTPA-enhanced MR cholangiography: Comparison with T2-weighted MR cholangiography. Eur Radiol 23(10):2713–2722, 2013. 64. Kapoor V, Baron RL, Peterson MS: Bile leaks after surgery. AJR Am J Roentgenol 182:451–458, 2004. 65. Kasahara M, Ueda M, Haga H, et al: Living-donor liver transplantation for hepatoblastoma. Am J Transplant 5:2229–2235, 2005. 66. Kayahan Ulu EM, Coskun M, Ozbek O, et al: Accuracy of multidetector computed tomographic angiography for detecting hepatic artery complications after liver transplantation. Transplant Proc 39(10):3239– 3244, 2007. 67. Kim BS, Kim TK, Jung DJ, et al: Vascular complications after living related liver transplantation: Evaluation with gadolinium-enhanced three-dimensional MR angiography. AJR Am J Roentgenol 181:467–474, 2003. 68. Kim HJ, Kim KW, Kim AY, et al: Hepatic artery pseudoaneurysms in adult living-donor liver transplantation: Eficacy of CT and Doppler sonography. AJR Am J Roentgenol 184:1549–1555, 2005. 69. Kim SY, Kim KW, Kim MJ, et al: Multidetector row CT of various hepatic artery complications after living donor liver transplantation. Abdom Imaging 32:635–643, 2007. 70. Kim BW, Won JH, Lee BM, et al: Intraarterial thrombolytic treatment for hepatic artery thrombosis immediately after living donor liver transplantation. Transplant Proc 38:3128–3131, 2006. 71. Kishi Y, Sugawara Y, Kaneko J, et al: Classiication of portal vein anatomy for partial liver transplantation. Transplant Proc 36:3075–3076, 2004. 72. Kiuchi T, Kasahara M, Uryuhara K, et al: Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 67:321–327, 1999. 73. Kobori L, van der Kolk MJ, de Jong KP, et al: Splenic artery aneurysms in liver transplant patients. Liver Transplant Group. J Hepatol 27:890–893, 1997. 74. Kodama Y, Sakuhara Y, Abo D, et al: Percutaneous transluminal angioplasty for hepatic artery stenosis after living donor liver transplantation. Liver Transpl 12:465–469, 2006. 75. Kooby DA, Fong Y, Suriawinata A, et al: Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg 7:1034–1044, 2003. 76. Kwon CH, Joh JW, Lee KW, et al: Safety of donors with fatty liver in liver transplantation. Transplant Proc 38:2106–2107, 2006. 77. Lang H, Oldhafer KJ, Weimann A, et al: Liver transplantation for metastatic neuroendocrine tumors. Ann Surg 225:347–354, 1997. 78. Lang P, Schnarkowski P, Grampp S, et al: Liver transplantation: Signiicance of the periportal collar on MRI. J Comput Assist Tomogr 19:580–585, 1995. 79. Lee J, Ben-Ami T, Yousefzadeh D, et al: Extrahepatic portal vein stenosis in recipients of living-donor allografts: Doppler sonography. AJR Am J Roentgenol 167:85–90, 1996. 80. Lee SS, Kim TK, Byun JH, et al: Hepatic arteries in potential donors for living related liver transplantation: Evaluation with multi-detector row CT angiography. Radiology 227:391–399, 2003. 81. Lee VS, Krinsky GA, Nazzaro CA, et al: Deining intrahepatic biliary anatomy in living liver transplant donor candidates at mangafodipir trisodium-enhanced MR cholangiography versus conventional T2-weighted MR cholangiography. Radiology 233:659–666, 2004. 82. Lee SW, Park SH, Kim KW, et al: Unenhanced CT for assessment of macrovesicular hepatic steatosis in living liver donors: Comparison of

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visual grading with liver attenuation index. Radiology 244:479–485, 2007. Lerut JP, Orlando G, Sempoux C, et al: Hepatic haemangioendothelioma in adults: Excellent outcome following liver transplantation. Transpl Int 17:202–207, 2004. Letourneau JG, Day DL, Ascher NL, et al: Abdominal sonography after hepatic transplantation: Results in 36 patients. AJR Am J Roentgenol 149:299–303, 1987. Liu B, Yan LN, Wang WT, et al: Clinical study on safety of adult-toadult living donor liver transplantation in both donors and recipients. World J Gastroenterol 13:955–959, 2007. Lo CM, Fan ST, Liu CL, et al: Adult-to-adult living donor liver transplantation using extended right lobe grafts. Ann Surg 226:261–269, 1997. Lowell JA, Coopersmith CM, Shenoy S, et al: Unusual presentations of nonmycotic hepatic artery pseudoaneurysms after liver transplantation. Liver Transpl Surg 5:200–203, 1999. Lubienski A: Hepatocellular carcinoma: Interventional bridging to liver transplantation. Transplantation 80(1 Suppl):S113–S119, 2005. Makowka L, Stieber AC, Sher L, et al: Surgical technique of orthotopic liver transplantation. Gastroenterol Clin North Am 17:33–51, 1988. Malhi H, Gores GJ: Review article: The modern diagnosis and therapy of cholangiocarcinoma. Aliment Pharmacol Ther 23:1287–1296, 2006. Marcos A, Ham JM, Fisher RA, et al: Surgical management of anatomical variations of the right lobe in living donor liver transplantation. Ann Surg 231:824–831, 2000. Marshall MM, Muiesan P, Srinivasan P, et al: Hepatic artery pseudoaneurysms following liver transplantation: Incidence, presenting features and management. Clin Radiol 56:579–587, 2001. Marsman WA, Wiesner RH, Rodriguez L, et al: Use of fatty donor liver is associated with diminished early patient and graft survival. Transplantation 62:1246–1251, 1996. Martin P, DiMartini A, Feng S, et al: Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology 59(3):1144–1165, 2014. Matsubara K, Cho A, Okazumi S, et al: Anatomy of the middle hepatic vein: Applications to living donor liver transplantation. Hepatogastroenterology 53:933–937, 2006. Mazzaferro V, Regalia E, Doci R, et al: Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699, 1996. Michels NA: Newer anatomy of the liver and its variant blood supply and collateral circulation. Am J Surg 112:337–347, 1966. Miro JM, Aguero F, Laguno M, et al: Liver transplantation in HIV/ hepatitis co-infection. J HIV Ther 12:24–35, 2007. Molmenti EP, Pinto PA, Klein J, et al: Normal and variant arterial supply of the liver and gallbladder. Pediatr Transplant 7:80–82, 2003. Moon JI, Kwon CH, Joh JW, et al: Safety of small-for-size grafts in adult-to-adult living donor liver transplantation using the right lobe. Liver Transpl 16(7):864–869, 2010. Murray KF, Carithers RL, Jr: AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology 41:1407–1432, 2005. Navarro F, Le Moine MC, Fabre JM, et al: Speciic vascular complications of orthotopic liver transplantation with preservation of the retrohepatic vena cava: Review of 1361 cases. Transplantation 68:646–650, 1999. Nemec P, Ondrasek J, Studenik P, et al: Biliary complications in liver transplantation. Ann Transplant 6:24–28, 2001. Nghiem HV: Imaging of hepatic transplantation. Radiol Clin North Am 36:429–443, 1998. O’Connor TP, Lewis WD, Jenkins RL: Biliary tract complications after liver transplantation. Arch Surg 130:312–317, 1995. Ohta M, Hashizume M, Tanoue K, et al: Splenic hyperkinetic state and splenic artery aneurysm in portal hypertension. Hepatogastroenterology 39:529–532, 1992. Pandey D, Lee KH, Tan KC: The role of liver transplantation for hilar cholangiocarcinoma. Hepatobiliary Pancreat Dis Int 6:248–253, 2007.

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108. Pandharipande PV, Lee VS, Morgan GR, et al: Vascular and extravascular complications of liver transplantation: Comprehensive evaluation with three-dimensional contrast-enhanced volumetric MR imaging and MR cholangiopancreatography. AJR Am J Roentgenol 177:1101–1107, 2001. 109. Parrilla P, Sánchez-Bueno F, Figueras J, et al: Analysis of the complications of the piggy-back technique in 1112 liver transplants. Transplantation 67:1214–1217, 1999. 110. Parry SD, Muiesan P: Cholangiopathy and the biliary cast syndrome. Eur J Gastroenterol Hepatol 15:341–343, 2003. 111. Pascher A, Neuhaus P: Bile duct complications after liver transplantation. Transpl Int 18:627–642, 2005. 112. Pieters PC, Miller WJ, DeMeo JH: Evaluation of the portal venous system: Complementary roles of invasive and noninvasive imaging strategies. Radiographics 17:879–895, 1997. 113. Platt JF, Rubin JM, Ellis JH: Hepatic artery resistance changes in portal vein thrombosis. Radiology 196:95–98, 1995. 114. Platt JF, Yutzy GG, Bude RO, et al: Use of Doppler sonography for revealing hepatic artery stenosis in liver transplant recipients. AJR Am J Roentgenol 168:473–476, 1997. 115. Prokesch RW, Schima W, Berlakovich G, et al: Adrenal hemorrhage after orthotopic liver transplantation: MR appearance. Eur Radiol 11:2484–2487, 2001. 116. Puente SG, Bannura GC: Radiological anatomy of the biliary tract: Variations and congenital abnormalities. World J Surg 7:271–276, 1983. 117. Rea DJ, Heimbach JK, Rosen CB, et al: Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg 242:451–458, 2005. 118. Reddy KS, Johnston TD, Putnam LA, et al: Piggyback technique and selective use of veno-venous bypass in adult orthotopic liver transplantation. Clin Transplant 14:370–374, 2000. 119. Rossi AR, Pozniak MA, Zarvan NP: Upper inferior vena caval anastomotic stenosis in liver transplant recipients: Doppler US diagnosis. Radiology 187:387–389, 1993. 120. Rustgi VK: The epidemiology of hepatitis C infection in the United States. J Gastroenterol 42:513–521, 2007. 121. Ryu CH, Lee SK: Biliary strictures after liver transplantation. Gut Liver 5(2):133–142, 2011. 122. Saad WE, Davies MG, Sahler L, et al: Hepatic artery stenosis in liver transplant recipients: Primary treatment with percutaneous transluminal angioplasty. J Vasc Interv Radiol 16:795–805, 2005. 123. Saggi BH, Farmer DG, Yersiz H, et al: Surgical advances in liver and bowel transplantation. Anesthesiol Clin North America 22:713–740, 2004. 124. Sanchez-Urdazpal L, Gores GJ, Ward EM, et al: Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation. Hepatology 17:605–609, 1993. 125. Sarmiento JM, Que FG: Hepatic surgery for metastases from neuroendocrine tumors. Surg Oncol Clin N Am 12:231–242, 2003. 126. Scarborough JE, Desai DM: Treatment options for biliary complications after orthotopic liver transplantation. Curr Treat Options Gastroenterol 10:81–89, 2007. 127. Schroeder T, Malagó M, Debatin JF, et al: “All-in-one” imaging protocols for the evaluation of potential living liver donors: Comparison of magnetic resonance imaging and multidetector computed tomography. Liver Transpl 11:776–787, 2005. 128. Seehofer D, Eurich D, Veltzke-Schlieker W, et al: Biliary complications after liver transplantation: Old problems and new challenges. Am J Transplant 13(2):253–265, 2013. 129. Shah JN, Haigh WG, Lee SP, et al: Biliary casts after orthotopic liver transplantation: Clinical factors, treatment, biochemical analysis. Am J Gastroenterol 98:1861–1867, 2003. 130. Sheng R, Sammon JK, Zajko AB, et al: Bile leak after hepatic transplantation: Cholangiographic features, prevalence, and clinical outcome. Radiology 192:413–416, 1994. 131. Sherman M: Hepatocellular carcinoma: Epidemiology, risk factors, and screening. Semin Liver Dis 25:143–154, 2005.

132. Shimoda M, Ghobrial RM, Carmody IC, et al: Predictors of survival after liver transplantation for hepatocellular carcinoma associated with hepatitis C. Liver Transpl 10:1478–1486, 2004. 133. Singh N: Infectious diseases in the liver transplant recipient. Semin Gastrointest Dis 9:136–146, 1998. 134. Soejima Y, Shimada M, Suehiro T, et al: Use of steatotic graft in living-donor liver transplantation. Transplantation 76:344–348, 2003. 135. Soejima Y, Taketomi A, Yoshizumi T, et al: Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma. Transplantation 83:893–899, 2007. 136. Solomon N, Sumkin J: Right adrenal gland hemorrhage as a complication of liver transplantation: CT appearance. J Comput Assist Tomogr 12:95–97, 1988. 137. Someda H, Moriyasu F, Fujimoto M, et al: Vascular complications in living related liver transplantation detected with intraoperative and postoperative Doppler US. J Hepatol 22:623–632, 1995. 138. Starzl TE, Iwatsuki S, Esquivel CO, et al: Reinements in the surgical technique of liver transplantation. Semin Liver Dis 5:349–356, 1985. 139. Starzl TE, Marchioro TL, Vonkaulla KN, et al: Homotransplantation of the liver in humans. Surg Gynecol Obstet 117:659–676, 1963. 140. Strouse PJ, Platt JF, Francis IR, et al: Tumorous intrahepatic lymphoproliferative disorder in transplanted livers. AJR Am J Roentgenol 167:1159–1162, 1996. 141. Sudan D, DeRoover A, Chinnakotla S, et al: Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2:774–779, 2002. 142. Tanaka K, Uemoto S, Tokunaga Y, et al: Surgical techniques and innovations in living related liver transplantation. Ann Surg 217:82–91, 1993. 143. Taourel P, Bret PM, Reinhold C, et al: Anatomic variants of the biliary tree: Diagnosis with MR cholangiopancreatography. Radiology 199:521–527, 1996. 144. Theilmann L, Küppers B, Kadmon M, et al: Biliary tract strictures after orthotopic liver transplantation: Diagnosis and management. Endoscopy 26:517–522, 1994. 145. Uslu N, Aslan H, Tore HG, et al: Doppler ultrasonography indings of splenic arterial steal syndrome after liver transplant. Exp Clin Transplant 10(4):363–367, 2012. 146. Vallejo GH, Romero CJ, de Vicente JC: Incidence and risk factors for cancer after liver transplantation. Crit Rev Oncol Hematol 56:87–99, 2005. 147. Valls C, Alba E, Cruz M, et al: Biliary complications after liver transplantation: Diagnosis with MR cholangiopancreatography. AJR Am J Roentgenol 184:812–820, 2005. 148. Varotti G, Gondolesi GE, Goldman J, et al: Anatomic variations in right liver living donors. J Am Coll Surg 198:577–582, 2004. 149. Verdonk RC, Buis CI, van der Jagt EJ, et al: Nonanastomotic biliary strictures after liver transplantation. Part 2. Management, outcome, and risk factors for disease progression. Liver Transpl 13:725–732, 2007. 150. Vit A, De Candia A, Como G, et al: Doppler evaluation of arterial complications of adult orthotopic liver transplantation. J Clin Ultrasound 31:339–345, 2003. 151. Vivarelli M, Cucchetti A, La Barba G, et al: Ischemic arterial complications after liver transplantation in the adult: Multivariate analysis of risk factors. Arch Surg 139(10):1069–1074, 2004. 152. Waki K: UNOS Liver Registry: Ten year survivals. Clin Transpl 29–39, 2006. 153. Wall WJ: Liver transplantation for hepatic and biliary malignancy. Semin Liver Dis 20:425–436, 2000. 154. Wang F, Pan KT, Chu SY, et al: Preoperative estimation of the liver graft weight in adult right lobe living donor liver transplantation using maximal portal vein diameters. Liver Transpl 17(4):373–380, 2011. 155. Williams ED, Draganov PV: Endoscopic management of biliary strictures after liver transplantation. World J Gastroenterol 15(30):3725– 3733, 2009. 156. Worthy SA, Olliff JF, Olliff SP, et al: Color low Doppler ultrasound diagnosis of a pseudoaneurysm of the hepatic artery following liver transplantation. J Clin Ultrasound 22:461–465, 1994.

CHAPTER 45 157. Yerdel MA, Gunson B, Mirza D, et al: Portal vein thrombosis in adults undergoing liver transplantation: Risk factors, screening, management, and outcome. Transplantation 69:1873–1881, 2000. 158. Yu AS, Keeffe EB: Patient selection criteria for liver transplantation. Minerva Chir 58:635–648, 2003. 159. Zajko AB, Bennett MJ, Campbell WL, et al: Mucocele of the cystic duct remnant in eight liver transplant recipients: Findings at cholangiography, CT, and US. Radiology 177:691–693, 1990. 160. Zajko AB, Campbell WL, Logsdon GA, et al: Cholangiographic indings in hepatic artery occlusion after liver transplantation. AJR Am J Roentgenol 149:485–489, 1987.

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161. Zajko AB, Sheng R, Bron K, et al: Percutaneous transluminal angioplasty of venous anastomotic stenoses complicating liver transplantation: Intermediate-term results. J Vasc Interv Radiol 5:121–126, 1994. 162. Zavaglia C, De Carlis L, Alberti AB, et al: Predictors of long-term survival after liver transplantation for hepatocellular carcinoma. Am J Gastroenterol 100:2708–2716, 2005. 163. Zhou J, Fan J, Wang JH, et al: Continuous transcatheter arterial thrombolysis for early hepatic artery thrombosis after liver transplantation. Transplant Proc 37:4426–4429, 2005.

46 Pancreas Manuel Patino, Andrea Prochowski, Nisha Sainani, Onofrio Catalano, and Dushyant Sahani

“I’m tired of all this nonsense about beauty being only skin-deep. What do you want, an adorable pancreas?” —Jean Kerr Whether the pancreas is adorable or not is a debatable issue; however, advanced cross-sectional imaging has permitted generation of excellent and exquisite images of the pancreas, which in turn has contributed immensely to the assessment of pancreatic diseases. Ultrasonography (US) has been used to evaluate abdominal pathologies, and its advantages include wide availability, low cost, and lack of radiation. Despite signiicant improvements and reinements in ultrasound technology, there are still inherent limitations when imaging deep in the abdomen, especially in large patients. Detailed visualization and deinition of deeper and smaller structures and of subtle changes in density of the normal and abnormal pancreas are possible with images generated by multidetector computed tomography (MDCT) scanners. The scope of multiplanar reconstruction with MDCT scanners has added remarkably to the ability to visualize and understand complex anatomic structures and relationships. Dual-energy CT (DECT) technology, recently introduced, allows generation of material-density images founded on energy-based material separation, providing information about iodine distribution and tissue composition. In addition, processed energy-speciic images can increase iodine enhancement, improving pancreatic lesion detection and characterization by increasing contrast between normal and abnormal tissue. Positron emission tomography (PET) CT allows the revelation of pathology at the molecular level. In addition, with the development of magnetic resonance hardware as well as new sequences and techniques, pancreatic parenchyma, ductal components, and relationships with surrounding structures can be deined with great detail. Even subtle lesions that do not alter the size and shape of the pancreas can be identiied with highquality magnetic resonance imaging (MRI). Expertise in these modalities varies, although there is signiicant overlap in the information they can disclose.

ANATOMY The pancreas is an exocrine and endocrine organ approximately 15 cm long that is related to the stomach, duodenum, colon, and spleen. Considerable variations in pancreatic size, shape, and location are possible depending on body habitus and size and the position of contiguous organs (Figs. 46-1 to 46-9; Tables 46-1 to 46-3).

CT Anatomy The density of the nonenhanced pancreas is normally the same as that of soft tissue, between 30 and 50 Hounsield units (HU); it increases to 100 to 150 HU after intravenous (IV) administration of iodine-

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based contrast agents.136,159 Rapid acquisition of images after a bolus injection allows visualization of normal enhancement during arterial, capillary, and venous phases. Homogeneous enhancement of the normal gland is a useful sign for excluding necrosis in pancreatitis. In the normal gland, variable normal fat tissue may be present, either along the margin of the gland or within the glandular portions. Fatty degeneration of the pancreas is common with aging; the entire pancreas may be replaced by fat, and the patient may have no clinical symptoms. Some pathologic conditions, such as chronic pancreatitis and cystic ibrosis, however, produce fatty iniltration and atrophy. The pancreas does not have a true ibrous capsule, and its contours may be smooth or lobular (Fig. 46-10). The pancreas is well visualized when peripancreatic retroperitoneal fat is abundant. The conspicuity of the gland can be improved in lean individuals and pediatric patients by the use of adequate oral contrast for opacifying the lumen of the stomach and bowel loops and by the use of IV contrast material for visualizing the vascular structures and pancreatic parenchyma.

MRI Anatomy The appearance of the pancreas on MRI depends on the speciic pulse sequence. On T1-weighted images, the normal gland, owing to the aqueous protein content, reveals higher signal intensity than nonfatty tissue such as liver and muscle. On fat-suppressed T1-weighted sequences, the relatively high signal intensity of the pancreas increases further (Fig. 46-11B). On T2-weighted sequences, the normal pancreas is slightly hyperintense to muscle, whereas on fat-suppressed T2-weighted images, the contrast between the normal pancreas and surrounding suppressed fat is minimal (see Fig. 46-11A).229,269 The vessels are seen as low voids on MRI (see Fig. 46-11C). On T1-weighted in-phase gradient echo (GRE) images, the pancreas appears hyperintense owing to the fat content, whereas it loses signal on T1-weighted opposed-phase images (see Fig. 46-11C and 46-11D). Being a very vascular organ, the pancreas shows intense contrast enhancement in the arterial phase, followed by a rapid washout (Fig. 46-12). This makes arterial-phase imaging crucial for accurate detection of most focal pancreatic lesions, which usually enhance less than the normal parenchyma and hence are rendered more conspicuous.117 The normal pancreatic duct measures 2 to 3 mm in caliber, demonstrates smooth margins, and increases slightly from the pancreatic tail to the head. The main pancreatic duct is routinely visualized on T2-weighted images and MR cholangiopancreatography (MRCP) as a high-signal-intensity structure (Fig. 46-13). Reviewing the source images and creating a maximum intensity projection (MIP) image can aid in visualizing and evaluating the entire duct (Fig. 46-14). The pancreatic duct receives 20 to 35 short tributaries or side branches that enter at right angles. These Text continued on p. 1415

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H

F

FIG 46-1 Normal anatomy of the pancreas. A to I, Axial CT sections of the pancreas from superior to inferior. A and B, Superior portion of the body of the pancreas (B) with the splenic artery (Spl.art) posterior to the body. The splenic artery is a branch of the celiac artery (CA), which in turns arises from the aorta (A). IVC, inferior vena cava. C and D, The oblique orientation of the long axis of the pancreas is seen with the tail (T) extending from the hilum toward the midline of the body (B). The body continues as the neck (N) anterior to the portal vein (PV) and superior mesenteric artery (SMA), which in turn continues as the head. E and F, The head lies in the C loop of the duodenum, bound superiorly by the bulb and medially by the second part of the duodenum (2nd). The common bile duct is seen as a low-density structure posterior to the head (H) of the pancreas (arrow in F). Branches of the pancreaticoduodenal arcade are seen around the head of the pancreas. Continued

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SMV SMA U IVC

G

H

I FIG 46-1, cont’d G and H, The head lies anterior to the inferior vena cava (IVC) and is bound medially by the superior mesenteric vein (SMV). The head turns around and inferiorly to the triangular uncinate process (U), which lies posterior to the superior mesenteric artery (SMA) and vein. I, The inferiormost portion of the uncinate process is seen anterior to the superior mesenteric artery and vein.

FIG 46-2 Coronal reformatted MDCT of the pancreas reveals a normal

FIG 46-3 Axial MDCT shows a normal gradually tapering pancreas.

pancreatic groove. The pancreatic groove (arrow) is the region between the head of the pancreas and the C loop of the duodenum.

Most commonly the head is larger than either the body or the tail, with the tail being the narrowest.

CHAPTER 46

Pancreas

1409

A FIG 46-4 Axial MDCT of a dumbbell pancreas. In this variant the head and tail are larger, with a narrow neck.

B FIG 46-6 Curved axial (A) and coronal (B) reformatted MDCT images show the main pancreatic duct (duct of Wirsung) in its entirety.

A

B FIG 46-5 A, Bulbous and redundant body and tail of the pancreas (arrow) mimicking a mass lesion on axial MDCT. B, Axial T2-weighted MRI conirms the same inding (arrow) without any altered signal intensity.

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Spl. Art

CA

CHA

SMA SMA

B A

PV CHA

Spl. Art.

Spl. Vein

CA

C

FIG 46-7 High-quality MDCT angiographic images of the major vessels in relation to and supplying the pancreas. A, Coronal section shows the common hepatic artery (CHA) and splenic artery (Spl. Art) originating from the celiac artery (not shown). The proximal portion of the superior mesenteric artery (SMA) originating from the aorta is visualized. B, Sagittal section in another patient reveals the origin of the celiac artery (CA) and superior mesenteric artery (SMA) from the aorta. Calciied plaques are seen along the aorta. C, Axial section reveals the celiac artery (CA) originating from the aorta, which in turn gives off its major branches, the common hepatic artery (CHA) and the splenic artery (Spl. Art.). The portal vein (PV) and splenic vein (Spl. Vein) are also visualized.

Spl. Art N H SMA Branch vessels

U SMA SMV

FIG 46-9 Coronal reformatted MDCT reveals the head (H), neck (N), and uncinate process (U) of the pancreas. The superior mesenteric artery (SMA) arises from the aorta posterior to the neck of the pancreas and runs inferiorly, anterior to the uncinate process, along with the superior mesenteric vein (SMV).

FIG 46-8 Coronal MDCT angiography reveals parenchymal feeding vessels in the region of the pancreatic head. The superior mesenteric artery (SMA) and splenic artery (Spl. Art) are visualized.

CHAPTER 46 Pancreas TABLE 46-1

Anatomic Relationships of

the Pancreas • Located in anterior pararenal space of retroperitoneum • Anterior to perirenal (Gerota’s) fascia and posterior to parietal peritoneum • Divided into head, uncinate process, neck, body, and tail from right to left (see Fig. 46-1) • Long axis of body and tail of pancreas is in an oblique orientation extending from hilum of spleen to midline of the body, where pancreas lies anterior to portal vein, which is the point of transition from the body to the neck (see Fig. 46-1C-F). • Region between head of pancreas and C loop of duodenum is known as the pancreatic groove (see Fig. 46-2). • In postnephrectomy cases or with agenesis of kidney or ectopic kidney, pancreas moves posteriorly to partially ill in the empty renal fossa; its soft tissue density should not be mistaken for recurrent tumor. Head • Located in C loop of duodenum • Bounded superiorly by the bulb • Laterally by second portion of duodenum • Inferiorly by third portion of duodenum • Medially by superior mesenteric vein • Anterior to inferior vena cava (see Fig. 46-1E-G) Uncinate process • Inferiormost portion of head of pancreas • Triangular or wedge shaped • Lies just posterior to superior mesenteric artery and vein (see Fig. 46-1G-I) Neck • Anterior to superior mesenteric artery • Vary greatly in thickness (see Fig. 46-1B-D) Tail • Anterior to splenic vein • Reaches splenic hilum (see Fig. 46-1C)

TABLE 46-2

1411

Pancreatic Ductal System

• With curved reformats created using multislice CT scanners, entire pancreatic duct can be visualized in a single plane (see Fig. 46-6). • Course of pancreatic duct can vary considerably; most commonly it is descending (50% of cases). • At the point of embryologic fusion of ducts of Santorini and Wirsung in pancreatic neck, the duct may narrow slightly or demonstrate a loop that may be confused with a stricture. Main Pancreatic Duct (Duct of Wirsung)

Accessory Pancreatic Duct (Duct of Santorini)

• Fusion of dorsal duct in body and tail, with ventral duct in uncinate process • Joins common bile duct at ampulla of Vater • Empties into duodenum through major papilla • Major drainage route in 91% of individuals174

• Located in upper portion (head) of pancreas • More horizontal than duct of Wirsung • Drains proximal to major papilla, in minor papilla • Present in 44% of individuals • Major drainage route in 9% of individuals174

Size • Anteroposterior measurements in CT140: • Head: 23 ± 3 mm • Neck: 19 ± 2.5 mm • Body: 20 ± 3 mm • Tail: 15 ± 2.5 mm • Ultrasound measurements tend to be smaller. • Gland shrinks with age, but head-to-body ratio remains almost constant181 Shape • Pancreas can have several basic shapes. • Most common is gradually tapering pancreas: head larger than body and tail (see Fig. 46-3) • Dumbbell-shaped pancreas: large head and tail, narrow neck (see Fig. 46-4) • Both ends should be about equal in size. • If one end is larger than the other, pathologic process should be considered (see Fig. 46-5).

FIG 46-10 Axial curved reformatted MDCT of the entire pancreas reveals a lobulated contour (the pancreas lacks a true ibrous capsule).

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TABLE 46-3

CT and MR Imaging of the Whole Body

Pancreatic Vascular Anatomy

• High-quality angiographic representation can be reconstructed using MDCT and angiography (see Fig. 46-7) in which not only major vessels but also tiny branches and parenchymal feeding vessels can be seen (see Fig. 46-8). • Calciications commonly occur in splenic artery and should not be mistaken for pancreatic calciications. Arterial Blood Supply

Veins of the Pancreas

From arteries originating from celiac and superior mesenteric arteries Celiac trunk is located superior to body of pancreas Splenic artery (branch of the celiac) courses along superior margin of pancreas Superior mesenteric artery (SMA) arises from aorta posterior to neck of pancreas and runs inferiorly, anterior to uncinate process, along with superior mesenteric vein (SMV) (see Fig. 46-9) • Main arteries are almost always present, but origin, size, and type of collateral supply may vary • Dorsal pancreatic • Great pancreatic • Transverse pancreatic • Pancreaticoduodenal arcade • Anterior and posterior superior pancreaticoduodenal branches of gastroduodenal artery anastomose with corresponding inferior pancreaticoduodenal branches of SMA to form an arterial arcade around head of pancreas

• Splenic vein runs along posterior and superior aspects of pancreas along with splenic artery • Splenic vein joins SMV behind neck of pancreas to form portal vein • Draining veins are parallel to arteries • Veins drain into pancreaticoduodenal, superior mesenteric, splenic, or portal veins • When pathologic occlusion of any of these vessels occurs, collateral vessels may enlarge and become visible.

• • • •

Lymphatic Drainage • Parallels venous drainage • Small lymph nodes around vessels and in various ligaments are commonly seen. However, if nodes are ≥10 mm, neoplasm should be suspected.

A

B

C

D FIG 46-11 A, Axial T2-weighted fat-suppressed image reveals the normal pancreas to be mildly hyperintense compared with liver and muscle. B, Axial T1-weighted fat-suppressed GRE image reveals a high-signalintensity pancreas compared with liver and muscle. C, The pancreas appears hyperintense on this axial T1-weighed GRE in-phase image owing to its fat content. Flow voids in the vessels (splenic artery and portal vein) are visualized (arrows). D, The pancreas loses its signal on the opposed-phase image.

CHAPTER 46

A

Pancreas

B FIG 46-12 Axial T1-weighted fat-suppressed noncontrast (A) and postcontrast (B) GRE images. The contrastenhanced image shows bright signal in the aorta and splenic artery (arrow) and intense contrast enhancement of the pancreas.

A

B FIG 46-13 Axial (A) and coronal (B) T2-weighted images reveal the normal pancreas and the pancreatic duct partially (arrow).

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A

B

C

D

E

F

FIG 46-14 Multisection coronal T2-weighted thin-slab single-shot FSE MRCP. A to F, Series of contiguous thin sections (generally 4 mm thick) acquired in the coronal plane with respiratory triggering; the images were acquired during expiration to allow motion-free imaging. When viewed sequentially, they reveal the pancreatic duct (arrow) and adjacent organ structures. A small pancreatic cyst (thick arrow in F) is seen inferior to the main pancreatic duct in the region of the uncinate process.

CHAPTER 46 Pancreas

1415

A B

C FIG 46-15 Pancreas divisum type 1. A, Curved coronal reformatted MDCT image. B, Curved axial reformatted MDCT image. C, MRCP in a patient with pancreas divisum. The dorsal duct system (arrowheads in A, B, and C) drains through the duct of Santorini (thin arrow in A and C) into the minor papilla and above the opening of the duct of Wirsung (black arrow in C) into the major papilla. Note the conluence of the duct of Wirsung (black arrow) with the common bile duct (thick arrow in C).

side branches are not usually seen on MRI or MRCP unless they are dilated.84 Visualization of the pancreatic duct and its side branches on MRCP can be enhanced by administration of secretin.166

Embryology and Developmental Anomalies and Variants Congenital anomalies of the pancreas are usually discovered in childhood, although some may be detected later in life owing to the development of clinical symptoms related to the anomaly itself or symptoms mimicking acquired diseases, mainly pancreatic cancer (Figs. 46-15 to 46-21; Table 46-4).

IMAGING TECHNIQUES CT Protocols and Technique Biphasic pancreatic MDCT (pancreatic parenchymal phase [PP] and a portal venous phase [PVP] of contrast enhancement) is considered the most sensitive technique for both detection and staging of pancreatic adenocarcinoma (PDAC).76 It can also be applied to evaluation of other pathologies such as pancreatic cystic tumors. Both maximal pancreatic parenchymal enhancement and maximal tumor-toparenchyma attenuation differences usually occur in the PP, which is therefore the most sensitive phase to detect PDAC. Although tumorto-parenchyma attenuation differences tend to decrease during the PVP, the sensitivity for vascular invasion is highest in the PVP of dynamic imaging.76 Scan delays for PP and PVP can be ixed or established on an individual basis according to the patient’s personal

hemodynamics and injection rate. With the irst approach a scan delay of 40 to 50 and 65 to 70 seconds is typically used for the PP and PVP, respectively. Nowadays, with the ability to scan the whole pancreas in less than 4 seconds and the possibility of scanning before consistent parenchymal enhancement has been achieved, such ixed delays may be inappropriate in many patients.228 The contrast material injection rate must also be taken into account when choosing the scanning protocol. It has been demonstrated that increasing the contrast injection rate shortens the aortic transit time, increases peak parenchymal pancreatic attenuation, does not change adenocarcinoma mean attenuation, and therefore increases the conspicuity of the tumor against the better-enhanced pancreatic parenchyma. It has also been demonstrated that individualized scan delays perform better than ixed ones.228 Usually 500 mL of water as a neutral contrast agent is given to the patient 20 to 30 minutes before the examination, and another 250 mL is given just before the start of the scan to achieve distention of the stomach and duodenum and improve detection of pancreatic abnormalities and iniltration or extension into surrounding anatomic structures, without masking common bile duct stones, pancreatic duct stones, or calciications.253 A noncontrast examination of the abdomen is performed to detect calciications and to clearly determine the location and extension of the pancreas in each patient. Subsequently, a PP acquisition extending from the diaphragm to below the third portion of the duodenum, and a PVP scan covering the whole abdomen are performed. The technical parameters used for each of these phases are detailed in Table 46-5. The raw data are subsequently

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CT and MR Imaging of the Whole Body processed to obtain multiplanar reconstructions, including MIPs and curved reconstructions along the course of the pancreatic duct. Using a structured report template helps ensure a complete description and reporting of imaging indings.31

Dual-Energy CT

A

B FIG 46-16 Pancreas divisum type 3. A, On MRCP the small ilamentous communication between the ventral (arrow) and dorsal (arrowhead) pancreatic duct system is not visualized. B, On the corresponding ERCP the small communication (arrow) between the dorsal (two arrowheads) and ventral (single arrowhead) duct systems is displayed.

DECT technology has been recently introduced into clinical practice, allowing new applications including material decomposition on the basis of energy-dependent attenuation proiles of speciic materials. This application provides additional qualitative and quantitative information of iodine distribution and tissue composition. For instance, material density–iodine (MD-I) images can improve conspicuity of isodense pancreatic masses including PDAC (Fig. 46-22), inlammatory lesions, and small neuroendocrine tumors170 (Fig. 46-23). Moreover, margins and extension of pancreatic lesions are more reliably deined along with a more accurate depiction of intralesional septa and nodules in cystic neoplasms (Fig. 46-24). MD-I images can contribute to the staging of pancreatic cancer because of the improved ability to assess vascular invasion, peripancreatic fat stranding, and distant metastasis. MD-I images can also improve characterization of surgical bed structures, allowing better differentiation between the postsurgical changes and local recurrence. Virtual unenhanced (VUE) images can be generated from contrast-enhanced acquisitions by a mathematical subtraction of the iodine. These images can substitute the true unenhanced images without losing depiction of small foci of calcium, fat, and hemorrhage, eliminating the need for unenhanced acquisition and reducing radiation dose1,93 (Fig. 46-25). DECT also offers the ability to generate virtual monochromatic (VMC) images. These processed images simulate CT acquisitions at different x-ray energies (keV), offering the ability to generate images at speciic energies (40 keV to 140 keV). Images created with energies around 70 keV are similar to those commonly acquired with single-energy (SE)CT (120 kVp). Low-kVp images increase conspicuity of hypoattenuating lesions by improving contrast between normal pancreas and abnormal tissue.155,160 DECT is a growing technology currently under research for different pancreatic diseases. However, efforts have focused on pancreatic cancer, owing to the diagnostic dificulties with SECT and the nature of the disease. Research studies have demonstrated better depiction of pancreatic cancer at low-energy images (52 keV) rather than images acquired at 120 kVp or processed at 70 keV. Text continued on p. 1421

*

A

B FIG 46-17 Annular pancreas. A, Axial T1-weighted fat-suppressed MRI demonstrates pancreatic tissue (arrows) completely circumscribing the descending portion of the duodenum (asterisk). B, Corresponding MRCP shows the extrinsic compression around the second portion of the duodenum (arrow).

CHAPTER 46

Pancreas

1417

* * A

B FIG 46-18 Pancreatitis in annular pancreas. Coronal FIESTA (fast imaging employing steady-state acquisition) image (A) and axial T1-weighted fat-suppressed image (B) display annular pancreas (arrows in A) encircling the second portion of the duodenum (asterisk). Normal pancreatic tissue reveals high signal intensity (arrow) on the T1-weighted image (B), whereas the inlamed tissue is hypointense (arrowhead).

*

FIG 46-19 Annular pancreas. MDCT shows the annular pancreas partially encircling and narrowing the second portion of the duodenum (arrow). The annular pancreas is uniform in density. The pancreatic duct is indicated by the arrowhead.

* *

*

FIG 46-20 Axial contrast-enhanced MDCT reveals complete agenesis of the dorsal pancreas. Note the rounded head of the pancreas (arrow) and the absence of the neck and body. Also note polysplenia (asterisks) and the abnormal position of the bowel loops (arrowheads) behind the stomach.

FIG 46-21 Axial contrast-enhanced MDCT reveals contour lobulations (asterisk) of the pancreatic head, extending horizontally and laterally to the pancreatic-duodenal artery (arrow). The lobulations have welldeined margins, no signs of iniltration of the surrounding structures, and a homogeneous density similar to that of the remaining normal pancreas.

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TABLE 46-4

CT and MR Imaging of the Whole Body

Embryology and Developmental Anomalies and Variants

Pancreas divisum

5% to 14% of population119 Failure of fusion of the dorsal and ventral ducts Separate drainage into duodenum Predominant drainage occurs through dorsal duct system (duct of Santorini). Classiied into three types (see Figs. 46-15 to 46-16): • I (classic form): complete lack of fusion between dorsal and ventral duct systems • II: absent duct of Wirsung • III: small communicating branch connects dorsal and ventral duct systems Increased incidence in patients with idiopathic pancreatitis Acute recurrent pancreatitis has been demonstrated in 49% of those with symptomatic pancreas divisum. ERCP: considered the gold standard for diagnosis of this entity MRCP: 73% accurate in diagnosing complete pancreas divisum MRCP is less accurate in diagnosis of incomplete pancreas divisum. MDCT, with the aid of multiplanar reconstructions, may be helpful in diagnosing pancreas divisum by depicting the dominant dorsal pancreatic duct draining directly into the minor papilla. On cross-sectional imaging, pancreatic tissue is homogeneous without focal areas of architectural distortion or altered texture.130,212

Annular pancreas

Occurs in 1 in 20,000 births Deined as a portion of pancreatic tissue in continuity with the head that partially or completely circumscribes duodenum Usually encircles second portion of duodenum (74% of cases), less often irst portion (21%), rarely third portion163 Usually associated with duodenal anomalies such as atresia, atrophy, or stenosis Up to 36% of patients with annular pancreas also have pancreas divisum.52,279 Usually discovered in childhood because of upper GI obstruction Classiied into six types depending on site of drainage of annular duct277 Type I (most common type): annular duct drains into major papilla after joining duct of Wirsung from dorsal side ERCP discloses an aberrant pancreatic duct encircling duodenum. Both MRI and MDCT reveal pancreatic tissue encircling duodenum, which retains density and signal intensity of remaining normal pancreas. T1-weighted fat-suppressed axial images are particularly useful. MRCP may disclose associated aberrant duct encircling duodenum and clearly shows extrinsic obstruction around second portion of duodenum (see Figs. 46-17 to 46-19). In adults, must be differentiated from locally iniltrating pancreatic or duodenal cancer

Agenesis of dorsal pancreas

Complete agenesis of pancreas incompatible with life Agenesis of dorsal pancreas is more frequent than agenesis of ventral pancreas. Agenesis of dorsal pancreas can be complete or partial (more common). Complete agenesis of the dorsal pancreas: body and tail of pancreas and whole dorsal duct system, including minor papilla and accessory duct, are absent. CT/MRI: visible head of pancreas retains normal pancreatic lobulations; density and signal intensity are homogeneous both at baseline study and following contrast administration. MRCP: pancreatic duct in head of pancreas is short; dorsal pancreatic duct and accessory duct cannot be found (see Fig. 46-20). Partial agenesis of the dorsal pancreas: distal part of pancreatic body or at least a remnant of accessory duct and minor papilla are found.150,180,227 Dorsal pancreatic agenesis is usually associated with other congenital variants (polysplenia syndrome, lobulation of the liver, intestinal malrotation). Recurrent or chronic pancreatitis occurs mainly in patients with partial agenesis. Diabetes is found in 67% of the cases. Agenesis of dorsal pancreas must be distinguished from reduction in size of pancreas due to pancreatitis and pancreatic cancer with upstream atrophy. If a dorsal duct of normal length is documented at MRCP, partial or complete agenesis of dorsal pancreas is ruled out and other possibilities need to be entertained.83,180

Pancreatic head lobulations

Contour anomalies of head and neck of pancreas composed of normal pancreatic tissue May be found isolated or in association with other anomalies Lobulations of head of the pancreas >1 cm in maximal dimension have been found in 35% of general population. Clinical relevance: possible misinterpretation of lobulations with pancreatic neoplasms CT and MRI demonstrate normal density and signal intensity of lobulations, paralleling characteristics of normal pancreas. Margins are well deined; no signs of iniltration of surrounding structures, bile duct dilatation, or vascular encasement (see Fig. 46-21) Lobulations classiied into three types according to their relation to gastroduodenal or pancreatic-duodenal artery: • Type 1: lobulation is directed anteriorly to artery. • Type 2: lobulation is directed posteriorly. • Type 3: lobulation is directed horizontally and laterally.217

CHAPTER 46 Pancreas TABLE 46-4 Ectopic pancreas

Uneven pancreatic lipomatosis

1419

Embryology and Developmental Anomalies and Variants—cont’d

May be found in different portions of GI tract Most commonly in proximal segments and Meckel’s diverticulum Tissue may be responsible for clinical symptoms related to secretion of pancreatic enzymes. Diagnosis not easy to make96 Not a congenital variant of pancreas Fatty iniltration of pancreas most common histologic change observed Age-related process that causes reduction in size of pancreas and increased evidence of its lobular structure Certain diseases (e.g., cystic ibrosis, diabetes) may be associated with increased fatty replacement of pancreas. When fatty replacement is focal or unevenly distributed through pancreas, condition is known as uneven pancreatic lipomatosis

TABLE 46-5

CT Scan Protocol for Pancreas Noncontrast (optional)

Parenchymal Phase

Portal Venous Phase

MDCT (16 and beyond) Thickness (mm) Interval (mm) FOV Tube Voltage (kV) Tube Current (mA) Delay Pitch Rotation Time Location

5 5 Large 120 80-160 — 1-1.5 0.5 Abdomen

1.25 0.625 Large 80-120 180-280 50 sec 1-1.5 0.5 Upper abdomen

5* 5* Large 80-120 180-280 70 sec 1-1.5 0.5 Abdomen

Coronal Reformats Thickness (mm) Interval (mm)

— —

1 0.6

3 3

*Retro-reconstructed to 1.25-mm thickness, 0.625-mm interval. FOV, ield-of-view; MDCT, multidetector computed tomography.

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A

B

C

D

FIG 46-22 Pancreatic adenocarcinoma on DECT. Axial contrast-enhanced SECT image (A), DECT-VMC image at 65 keV (B), MD-I image (C), and color overlay iodine image (D). It is challenging to detect the lesion in the tail of the pancreas in SECT images because of the similar attenuation between the lesion and the adjacent pancreatic tissue. DECT images improve detection of pancreatic lesions. Note improved contrast between the hypoattenuating lesion (arrows) and the surrounding parenchyma on low monochromatic energies (65 keV) and iodine images.

A

B

C

D

FIG 46-23 Pancreatic neuroendocrine tumor on DECT. Axial contrast-enhanced SECT image (A), DECT-VMC image at 65 keV (B), MD-I image (C), and color overlay iodine image (D). Note the improved visualization of the lesion in the pancreatic tail, best seen on iodine images.

CHAPTER 46 Pancreas

A

B

C

D

1421

FIG 46-24 Axial contrast-enhanced SECT image (A), DECT-VMC image at 65 keV (B), MD-I image (C), and color overlay iodine image (D). Note the presence of a 3-cm hypoattenuating lesion in the body of the pancreas. MD-I images help to characterize this lesion by improving visualization of lesion morphology and depiction of cystic lesions (borders and septa) and excluding the presence of solid component or enhancing nodules. The lesion was diagnosed as a serous cyst adenoma.

A

C

B

FIG 46-25 DECT virtual noncontrast images. Axial true unenhanced SECT image (A), DECT virtual unenhanced image (B), and DECT contrast-enhanced image (C). The virtual unenhanced images obtained from a contrast-enhanced DECT acquisition show similar image quality and diagnostic performance compared to true noncontrast images. VNC images can potentially eliminate the need of a true noncontrast series, reducing radiation exposure.

Although there is no consensus on a pancreatic DECT protocol, Table 46-6 outlines the approach used at our department for pancreatic diseases.

MRI Protocols and Technique The pancreas is best imaged with a high-ield-strength system (≥1.5 tesla [T]) and high-performance gradients that enable the use of fast MR sequences and phased-array torso coils.117,229 The protocol for MRI of the pancreas is detailed in Table 46-7.

T2-Weighted Images. Breath-hold or respiratory-triggered multisection, thin-slice, T2-weighted images are obtained in the axial and coronal planes. With these sequences, luid-illed lesions in or around the pancreas appear hyperintense; the common bile duct and the pancreatic duct are seen in cross sections and may be used to guide the acquisition of MRCP series. Fat suppression can increase the conspicuity of hyperintense lesions (see Fig. 46-11A).27

T1-Weighted Images. These images can be acquired either with a fast-spin

echo

(FSE)

T1-weighted

sequence

using

multiple

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TABLE 46-6

CT and MR Imaging of the Whole Body

DECT Pancreas Protocol

1 2 3

Administration of negative oral contrast + scout Administration of IV contrast media from 80-120 mL + 40 mL saline at 4 mL/sec CT phase Scan parameters Pancreatic phase (PP) (only abdomen) after PP 140 kVp 50 sec from injection Thickness/interval 2.5 mm/2.5 mm

4

Portal-venous phase (PVP) (abdomen and pelvis) after 70 sec from injection

PVP 120 kVp Thickness/interval 5 mm/5 mm

Generated images PP MD iodine VUE from PP PP VMC 50 keV + PP VMC 65 keV PP VMC 65 keV thickness/interval 1.25 mm/0.625 mm MIP and curved MPR reconstruction PP coronal + sagittal 3 mm PVP coronal + sagittal 3 mm/3 mm MIP and curved MPR reconstruction

keV, kilo-electron voltage; kVp, kilo-voltage peak; MD, material-density; VMC, virtual monochromatic; VUE, virtual unenhanced.

TABLE 46-7 MRI Localizer Precontrast

MRCP Presecretin Postsecretin* 3D MRCP

MRI Protocol for Pancreas

Sequence

Plane

Slice Thickness (mm)

Other Speciications

T1 (fast GRE) T2 (FSE) T1 (FSE or GRE) T1 in-phase/opposed-phase (GRE) T1 (GRE) T1 (GRE) delayed

Axial, coronal, sagittal Axial, coronal Axial Axial Axial, coronal Axial, coronal

4-6 4-6 4-6 4-6 4-6

± FS, BH/respiratory triggered ± FS, BH ± FS, BH Postcontrast FS, BH FS, BH

T2 2D MRCP (ssFSE—thin slab) T2 2D MRCP (ssFSE—thick slab) T2 2D MRCP (ssFSE—thick slab) T2 (ssFSE—thin slab)

Coronal, coronal oblique, axial Coronal, coronal oblique, axial Axial, coronal, coronal oblique Axial, coronal

4 20-50 20-50 1-1.5

BH BH BH, every 30 sec for 10-15 min BH

*Secretin is administered at a dose of 0.2 µg/kg intravenously (for >50 kg, 18.5 µg). BH, breath-hold; FS, fat-suppressed; FSE, fast-spin echo; GRE, gradient echo; MRCP, magnetic resonance cholangiopancreatography; ssFSE, single-shot fast-spin echo; 2D, two dimensional; 3D, three dimensional.

breath-hold acquisitions or with a single breath-hold GRE sequence with a water-stimulation prepulse, with or without fat suppression (see Fig. 46-11B). Fat suppression or selective water stimulation (1) improves delineation of the pancreas, which appears homogeneously bright compared with surrounding low-intensity fat; (2) is excellent for identifying a pancreatic mass or focal pancreatitis, which is less intense than the normal high-intensity pancreas; and (3) is suitable for contrast-enhanced studies. However, breath holding requires patient cooperation, and these sequences are less accurate in demonstrating focal disease in the presence of diffuse chronic pancreatitis because of the homogeneous low signal intensity of the ibrotic pancreas.27

Chemical Shift (In-Phase/Opposed-Phase) Imaging. A hypoattenuating lesion in the pancreas on contrast-enhanced CT is nonspeciic, and a non–border-deforming neoplasm cannot be ruled out. Although CT is accurate in revealing macroscopic fat (e.g., in pancreatic lipomas), it is less accurate in revealing microscopic lipid deposits. Fat-containing lesions in the pancreas have signal intensity similar to or higher than that of the remainder of the pancreas on in-phase T1-weighted GRE images (see Fig. 46-11C). This inding is in contradistinction to most pancreatic malignancies, which appear as areas of low signal intensity on T1-weighted sequences. Loss of signal intensity

on an opposed-phase T1-weighted GRE image establishes the lipid nature of the focal abnormalities (see Fig. 46-11D).110,122,269

Contrast-Enhanced MRI. A high-resolution axial and coronal dynamic breath-hold gadolinium (Gd)-enhanced (0.1 mmol/kg body weight) T1-weighted three-dimensional (3D) fast spoiled GRE sequence is used to detect and characterize pancreatic mass lesions and assess inlammatory processes such as pancreatitis. This allows a combination of pancreatic parenchymal evaluation and MR angiography to assess possible vascular involvement (see Fig. 46-12).166,176,210 The time required for contrast to reach the abdominal aorta can be determined by a test bolus injection, MR luoroscopy, or triggering software. Imaging at 15 seconds and 35 to 45 seconds after arrival of contrast in the abdominal aorta allows acquisition of high-quality images of pancreatic parenchyma and peripancreatic vessels.92 Alternatively a triplephase acquisition can be done by acquiring images in arterial (30-40 seconds), portal (70-80 seconds), and equilibrium (180 seconds) phases. Fat-suppressed high-resolution T1-weighted images acquired 10 minutes after administration of mangafodipir trisodium (5 µmol/ kg body weight) in a slow bolus over 1 to 2 minutes are useful for lesion detection in equivocal cases, for tumor detection, and for differentiating malignant from benign inlammatory masses.117 The basis for using mangafodipir is that normal pancreatic parenchyma enhances

CHAPTER 46 Pancreas following mangafodipir administration and becomes hyperintense on T1-weighted images, whereas tumors do not enhance.125

Magnetic Resonance Cholangiopancreatography MRCP has emerged as an accurate noninvasive means of evaluating the pancreatic duct. It uses heavily T2-weighted sequences that depict the luid-containing pancreatic duct as a high-signal-intensity structure. MRCP can be acquired as two-dimensional (2D) or 3D breathingaveraged or breath-hold FSE sequences and represents a viable alternative to diagnostic ERCP.84,85,126,163,166 Two different and complementary approaches are generally used for MRCP: a 2D thick-slab single-shot fast (turbo)-spin echo (ssFSE) T2-weighted sequence and a 3D multisection thin-slab T2-weighted sequence.84,163 An additional approach is secretin-enhanced MRCP, which is a particular thick-slab MRCP acquired before and after administration of secretin (Figs. 46-26 to 46-28; Table 46-8).

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Through a combined qualitative and semiquantitative evaluation, FDG PET CT can help in diagnosing pancreatic cancer when other imaging modalities are equivocal, characterizing lymph nodes, preoperative staging, depicting metastases and tumor recurrence, and monitoring response to therapy. Moreover, PET CT can have a role in

PET CT Technique Fused PET CT is a recently developed technology that combines the functional information of PET with the anatomic details of CT, providing both PET and contrast-enhanced CT images of the entire body in one setting.139,220 On PET studies, malignant lesions generally demonstrate avid luorine 18 (18F) luorodeoxyglucose (FDG) uptake, and most benign lesions are characterized by normal or minimal FDG uptake.25,199 However, false-positive and false-negative results may occur with FDG PET, and its inherent low spatial resolution may interfere with precise anatomic localization of the indings.215,262 Multidetector CT has the ability to image the entire abdomen and pelvis in a single breath hold with high spatial resolution, obtaining multiplanar reformats such as 3D and angiographic reconstructions, but it offers limited functional information. The limitations of CT for detection of pancreatic tumors are increasingly being recognized; a correlation between tumor size and sensitivity exists.248 Moreover about 10% of PDACs and pancreatic metastases are isoattenuating at contrast-enhanced CT and not depicted even when larger than 2 cm.209

A

FIG 46-26 Coronal T2-weighted thick-slab single-shot FSE MRCP provides an excellent display of the extrahepatic biliary tract and pancreatic duct. Residual luid is seen in the duodenum (short arrows), which can be avoided by fasting or using a T2-negative oral contrast medium. A small pancreatic cyst (long arrow) is seen inferior to the main pancreatic duct; there is a subtle long thin communication.

B FIG 46-27 A, Coronal T2-weighted single-shot FSE MRCP reveals a pancreatic cyst (short arrow) overlapping the pancreatic duct (long arrows). B, 3D MRCP with rotation of image plane helps separate the cystic lesion from the pancreatic duct (thin arrows) and reveals the short communication (thick arrow).

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A B

C FIG 46-28 A, Coronal MRCP reveals the pancreatic duct (arrowheads) and small hyperintense lesions (arrows) adjacent to the duct. These lesions probably represent side-branch intraductal papillary mucinous neoplasms (IPMNs); however, the communication with the pancreatic duct is not distinctly visualized. B and C, Postsecretin coronal projection in different planes improves the conspicuity of the pancreatic duct (arrowheads), side-branch IPMNs (arrows), and communication with the pancreatic duct (horizontal arrow in C).

diagnosing focal mass-forming autoimmune pancreatitis and guiding biopsy to sites that accurately represent the suspected pathology.220

PATHOLOGIC CONDITIONS Inlammatory Processes Acute Pancreatitis. Acute pancreatitis is an acute inlammatory process that is followed by complete restoration of structural and functional normalcy after the attack subsides, provided no part of the pancreas has been destroyed by necrosis.235 The most common causes of acute pancreatitis are choledocholithiasis and ethanol abuse. Other causes include trauma, metabolic disorders (hyperlipidemia, hypercalcemia), ERCP-induced pancreatitis, medications (azathioprine, sulfonamides), tumors, and congenital anomalies such as pancreas divisum.149 Most patients present with nausea, vomiting, abdominal pain, and rebound tenderness. Fever, tachycardia, and leukocytosis are often present. The diagnosis is usually established by detection of elevated levels of pancreatic enzymes in blood, urine, or both.8 Once the clinical diagnosis of acute pancreatitis is made, treatment depends on the initial assessment of disease stage and severity. An increased frequency of death from acute pancreatitis is directly correlated with the development of multiorgan failure and the extent of pancreatic necrosis, which is a grave prognostic indicator.19 Whereas mortality rates of less than

1% are reported in patients with interstitial pancreatitis, mortality increases dramatically to 10% to 23% in patients with necrotizing pancreatitis.20,28 Virtually all life-threatening complications occur in patients with necrotizing pancreatitis. Secondary bacterial contamination occurs in 40% to 70% of patients with pancreatic necrosis, and it constitutes a major risk for death.214 Classiication. Acute pancreatitis was initially classiied into mild acute (interstitial edematous) and severe acute (necrotizing) types.11,28 The classiication was recently revised and updated, distinguishing between two phases of acute pancreatitis: an early phase (within the irst week) and a late phase (after the irst week).251 The early phase is characterized by pancreatic inlammation with variable degrees of peripancreatic edema and ischemia that can resolve or progress to necrosis; this phase is deined by clinical parameters such as organ failure. Patients with organ failure that resolves in 48 hours are considered to have mild pancreatitis without complications and a mortality rate of 0%. Patients are considered to have severe acute pancreatitis if organ failure lasts for more than 48 hours, which carries an increased risk of complications. The late phase is characterized by increasing necrosis, infection, and persistent multiorgan failure. This phase is deined by a combination of imaging indings and clinical parameters.251 Contrast-enhanced CT is able to depict and quantify pancreatic parenchymal injury, except

CHAPTER 46 Pancreas TABLE 46-8

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Thick-Slab ssFSE T2-Weighted Sequence (Projective MRCP)

Multisection Thin-Slab ssFSE T2-Weighted Sequence

Two-dimensional single thick (20-50 mm) section that can be obtained in any plane with a single short breath hold (3 cm) MPD narrowing MPD dilatation not exceeding 4-5 mm Penetrating duct sign (dilated MPD penetrating the focal enlargement without disappearing) Halo sign Extrapancreatic indings Improvement of indings after corticosteroid therapy From Lee LK, Sahani DV: Autoimmune pancreatitis in the context of IgG4-related disease: Review of imaging indings. World J Gastroenterol 20:15177–15189, 2014. MPD, main pancreatic duct.

ibrosis and sclerosis are also responsible for pancreatic atrophy, which may be a long-term sequela in some cases (see Fig. 46-54). Findings on MR and MRCP in patients with typical AIP include a diffusely enlarged gland. As on CT, a peripheral rim of the hypointense halo can be seen on MRI. In addition, diffuse attenuation of the main pancreatic duct or a small strictured main pancreatic duct may be seen on MRCP.82 In patients with focal masslike lesions, ine-needle aspiration of the mass may be helpful. Because pathologic conirmation of AIP is dificult because of the patchy nature of the disease, corticosteroid therapy can be used as a diagnostic tool in patients whose clinical and laboratory indings are strongly suggestive of the disease. In these patients, short-interval imaging at 2 to 4 weeks after the initiation of therapy must be used to verify resolution of the mass145 (Box 46-1). However, because malignant masses may also respond to corticosteroids, complete resolution of the pancreatic mass is critical for the conirmation of AIP. If the clinical history and laboratory and pathologic indings do not support the diagnosis of AIP, or if corticosteroid therapy fails to resolve the pancreatic mass, surgical biopsy of the mass should be considered.73,86 Hereditary pancreatitis. Hereditary pancreatitis is an autosomal dominant relapsing pancreatitis with an estimated 80% penetrance. It generally manifests during childhood, with a peak incidence at age 5 years. However, a second peak at age 17 may be attributable to the introduction of alcohol in the diet. In addition, factors such as hyperlipidemia and hypercalcemia may play a role. The symptoms, signs, and pathophysiology of this type of pancreatitis are no different from those of the other types of pancreatitis discussed. Parenchymal and intraductal calciications occur in approximately 50% of patients. Intraductal calculi occur early in the course of the disease; they tend to be large and rounded and are arranged in a linear pattern in the dilated main pancreatic duct. Other features of pancreatitis and pseudocysts may be seen. Pancreatectomy is the treatment of choice.58,121,147

MRI in Pancreatitis. MRI has a very limited role in acute settings and is typically used as a problem-solving tool to answer a speciic clinical question. In acute pancreatitis, fat-suppressed T2-weighted images are helpful for deining subtle diffuse or focal parenchymal abnormalities. T2-weighted images can accurately depict luid collections, pseudocysts, and areas of hemorrhage. MRI can assess the internal consistency and drainability of luid collections, thus inluencing the choice of treatment.179 Gd-enhanced T1-weighted GRE MRI can

depict pancreatic necrosis as areas of nonenhanced parenchyma.7 MRCP has the advantage of demonstrating possible choledocholithiasis, the presence or absence of ductal disruption or leakage, and the size, location, and possible communication of a pseudocyst with the pancreatic duct, thus making it useful for therapeutic planning.163 In patients with recurrent pancreatitis, MRCP can demonstrate causative factors such as pancreas divisum and annular pancreas, especially if performed with secretin stimulation, without the risk of post-ERCP pancreatitis.164 In early stages of chronic pancreatitis, increased signal intensity on T2-weighted MRI is due to fatty and ibrous replacement, inlammatory cell iniltration of the pancreatic parenchyma, and impaired pancreatic juice outlow.49 Pre- and post-Gd fat-suppressed T1-weighted images in chronic pancreatitis reveal decreased enhancement in the arterial phase and increased enhancement in the early venous phase. The signal intensity ratio (postcontrast divided by precontrast signal intensity) in the arterial phase is signiicantly lower (180 degrees • Any solid tumor contact with CA • Solid tumor invading aorta • Solid tumor contact with irst SMA branch and most proximal draining vein into SMV Pancreatic body and tail: • Solid tumor contact of >180 degrees with SMA or CA • Solid tumor contact with aorta

No distant metastasis

Borderline tumors

Unresectable tumors

Pancreatic head/uncinate process: • Unreconstructible SMV or PV • SMV occlusion (can be due to tumor or bland thrombus) Pancreatic body and tail: • Unreconstructible SMV or PV • SMV occlusion (can be due to tumor or bland thrombus)

such as pancreatic intraepithelial neoplasm (PIN) and intraductal papillary mucinous neoplasm (IPMN). Although multiple oncogenes are activated through the progression pathway, KRAS activation is the most common oncogenic mutation in PDAC. KRAS mutation is associated with poor prognosis.192 Approximately 60% to 70% of PDACs occur in the head of the pancreas; the remainder are found in the body or tail or diffusely iniltrate the organ. PDAC is associated with an intense desmoplastic (stromal) reaction and tends to obstruct the pancreatic duct, with subsequent upstream duct dilatation and parenchymal atrophy; if it arises in the head, the common bile duct can be stenosed, with biliary tree dilatation. Pancreatic adenocarcinoma can extensively iniltrate the retroperitoneum and invade surrounding anatomic structures including the duodenum, stomach, mesenteric vessels, portal vein, neurovascular spaces, and lymphatic channels. It tends to metastasize to regional lymph nodes (at diagnosis, about 80% of cases of pancreatic head adenocarcinoma present with lymph node metastases), liver, and peritoneum.271 Because of the early occurrence of clinical symptoms, masses arising in the head of the pancreas tend to be smaller (2-3 cm in diameter) at diagnosis than those in the body and tail (5-7 cm in diameter).271 Clinical presentation varies according to the cancer’s site of origin and stage, but many patients recall a history of long-standing abdominal pain, asthenia, reduced appetite, and weight loss. New-onset diabetes mellitus is present in 10% of patients. Painless jaundice is present in 75% of patients at presentation, mostly in the cases of tumors arising from the head of the pancreas.36,123 Tumors in the body and tail tend to present with back pain related to tumor iniltration of the surrounding retroperitoneal structures and nerves.271 Late clinical presentation with advanced disease and the tumor’s biological aggressiveness result in a low rate of surgical intervention (10%20%) and high mortality.205 Complete surgical resection along with adjuvant therapy remains the best curative treatment for pancreatic adenocarcinoma. Currently, less than 20% of patients are candidates for surgical resection, and the small tumors that are amenable to curative surgery are the

Distant metastasis (including nonregional lymph node metastasis)

most dificult to detect.21,36,103 The treatment approach is based on whether the tumor is resectable or nonresectable at presentation56,77 (Table 46-13). For locally advanced pancreatic cancer (Figs. 46-56 to 46-58), chemotherapy, radiotherapy, or both are alternatives to surgery.153,265 Patients with distant metastases are considered ineligible for radiation treatment and undergo chemotherapy alone, although the traditional chemotherapy regimen for pancreatic adenocarcinoma, based on 5-luorouracil (5-FU) or gentamicin, offers only a small survival advantage and only a slight improvement in the quality of life.103,242 Despite the fact that tumor serum marker CA 19-9 is considered a sensitive but nonspeciic marker for the diagnosis of adenocarcinoma of the pancreas, it is rarely positive in tumors less than 1 cm in diameter.203,271 Therefore diagnostic imaging plays a critical role in the evaluation of this disease. Multiphasic MDCT plays a major role in the assessment of pancreatic adenocarcinoma. Moreover, advanced CT technology such as DECT has become a commonly used imaging modality for evaluation of PDAC. Additional imaging techniques for diagnosis and staging include US, MRI, PET CT, ERCP, and endoscopic ultrasound (EUS). The diagnostic imaging approach to PDAC depends on the clinical indications: (1) patients who are clinically suspected of having pancreatic cancer and need diagnostic imaging to verify the presence or absence of disease, (2) patients who have already been diagnosed with PDAC and require staging, and (3) patients at high risk for this tumor who require screening. The TNM classiication for pancreatic cancer staging is presented in Box 46-2. Role of CT in screening. About 5% to 10% of pancreatic cancers are due to hereditary factors. For patients with a irst-degree relative affected with pancreatic cancer, the relative risk for developing pancreatic cancer increases 2 to 6 times. Also, members of families with a history of hereditary cancer syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast and ovarian cancer syndrome, familial atypical multiple mole melanoma syndrome, and hereditary nonpolyposis colorectal cancer are at increased risk of developing pancreatic cancer. In these cases, close follow-up might lead

CHAPTER 46 Pancreas to detection of tumors at an early stage and an improvement in overall survival.55 Although there is consensus in the need of screening in patients with a predisposition for pancreatic cancer, there is no consensus regarding the most effective modality for screening or the appropriate time interval between the screenings.56

FIG 46-56 Adenocarcinoma of the pancreas. Axial contrast-enhanced pancreatic-phase image shows a poorly deined area of hypodensity in the neck and body of the pancreas (white arrow) iniltrating the retroperitoneum. The superior mesenteric vein is severely reduced in caliber, is circumscribed by the lesion for more than 180 degrees, and is teardrop shaped (black arrow), suggesting iniltration.

Role of MDCT. MDCT allows the pancreas to be imaged at high spatial and temporal resolution within a short breath hold.88,203 Contrast enhancement time is crucial in tumor detection. It has been demonstrated that both peak enhancement and time to peak enhancement of the pancreas are related to the contrast injection rate, and there is a strong positive correlation between pancreatic parenchymal

FIG 46-57 Adenocarcinoma of the pancreas. Axial contrast-enhanced PVP image shows a mass (arrows) in the neck and body of the pancreas, with poorly deined and iniltrating margins. The mass exhibits reduced and inhomogeneous contrast enhancement, and there is upstream dilatation of the pancreatic duct (single arrowhead). The mass surrounds the superior mesenteric artery (wavy arrow). Peritoneal luid and thickening (two arrowheads) represent metastatic implants.

SMA

A

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B FIG 46-58 Adenocarcinoma of the pancreas. Coronal contrast-enhanced (A) and coronal MIP (B) MDCT images demonstrate a mass in the head and uncinate process of the pancreas (white arrows). It appears hypodense after contrast administration, exhibits poorly deined margins, iniltrates surrounding fat tissue, and reduces the caliber of the superior mesenteric artery (SMA) (arrowheads). Multiple small, rounded, hypodense metastatic foci are seen in the liver (black arrows in A).

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enhancement and both the volume of contrast material and its rate of injection. A dual-phase (PP and PVP) pancreatic protocol for MDCT is a sensitive technique for detecting and staging PDAC and for detecting metastases to the liver and peritoneum. Time delays can be predetermined or calculated according to the patient’s hemodynamic

AJCC TNM Staging System for Pancreatic Cancer BOX 46-2

Primary Tumor (T) Primary tumor cannot be assessed Tx T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor limited to the pancreas, 2 cm or less in greatest dimension T2 Tumor limited to the pancreas, more than 2 cm in greatest dimension T3 Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery T4 Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor) Regional Lymph Nodes (N) Nx Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis (M) M0 No distant metastasis M1 Distant metastasis From Edge S et al (eds): AJCC cancer staging manual, ed 7, New York, 2010, Springer-Verlag.

parameters. In the case of a predetermined protocol, a scan delay of 40 to 50 seconds from the start of a bolus of IV contrast agent is used for the PP, and a scan delay of 65 to 70 seconds is used for the PVP.17,76,146 With 16-detector or higher MDCT scanners it is preferable to calculate delays based on the patient’s hemodynamics and injection rate. The PP allows optimal tumor detection and mapping of the regional vascular structures; in this phase the PDAC appears as a low-density lesion compared with the normal pancreatic parenchyma. In the PVP, the tumor conspicuity against the normal pancreas may be reduced owing to contrast diffusion into the interstitium of the tumor, but the detection of liver and peritoneal metastasis and the visualization of portal venous structures are improved.76,252 However, in about 10% of cases the mass is isoattenuating with contrast enhancement and cannot be directly observed. In these cases, useful indirect signs include stenosis of the distal common bile duct, stenosis of the pancreatic duct with upstream ductal dilatation, parenchymal atrophy, “double-duct” sign (stenosis of both the common bile duct and the pancreatic duct, with subsequent upstream dilatation), loss of lobulation of the pancreatic parenchyma, and deformity of the pancreatic contours.226 MDCT data can be postprocessed in various planes to maximize the diagnostic yield of the examination and improve visualization of the pancreatic vasculature and biliary structures. Among the different postprocessing techniques, MIP is particularly useful to display vascular structures; volume-rendered imaging is apt to depict both vessels and soft tissues. Multiplanar volume rendering and curved reconstructions, which can be constructed along the course of the pancreatic duct, provide MDCT pancreatograms17,75 (Figs. 46-59 to 46-61). MDCT pancreatograms allow one to follow the course of the dilated pancreatic duct, ind the site of obstruction, analyze the characteristics of the stenosis, and visualize the surrounding parenchyma. Preoperative vascular evaluation can be accurately performed with MDCT

* A

B

C FIG 46-59 Adenocarcinoma of the pancreas. A, Coronal PVP MDCT demonstrates a mass in the head and uncinate process of the pancreas (short arrows) iniltrating the third portion of the duodenum (long arrow) and surrounding the superior mesenteric artery (arrowhead). Coronal (B) and axial (C) curved reformatted images of the same patient display the tumor (arrows) and dilatation of the main pancreatic duct (arrowheads), which abruptly terminates in the mass. A biliary stent is seen in situ (asterisk).

CHAPTER 46 Pancreas angiography and constitutes a crucial part of the MDCT examination. Its purposes are avoidance of intraoperative vascular complications and accurate staging. The negative predictive value of MDCT for overall tumor resectability was found to be high (87%) in a recent study.259 The accuracy of MDCT (86%) in the assessment of global locoregional extension is higher than that of EUS (65%) and MRI (75%), owing to the superior visualization of fat iniltration. However, EUS was most accurate in the

FIG 46-60 Adenocarcinoma of the pancreas. Curved reformatted MDCT shows an oval mass in the tail of the pancreas, with ill-deined margins and poor enhancement (arrow).

A

1445

evaluation of duodenal iniltration (EUS, 76%; CT, 74%; MRI, 67%). In some studies, EUS had the highest overall accuracy with respect to tumor involvement of regional lymph nodes. MDCT is the modality with the highest global accuracy in the assessment of vascular invasion.236 The likelihood of vascular iniltration by adenocarcinoma of the pancreas increases with greater tumor-to-vessel circumference contact. The likelihood of vessel iniltration is less than 3% when the tumor-to-vessel circumference contact is less than 90 degrees; it is between 29% and 57% for contact between 90 and 180 degrees, and it is more than 80% for contact greater than 180 degrees.153,191 Other useful criteria that indicate vascular invasion are the teardrop sign, which refers to the shape of the portal vein or the superior mesenteric vein (SMV); the lack of preservation of a fat plane around the vessels; and dilatation of the pancreaticoduodenal veins (see Figs. 46-56 and 46-58).123,148,272 A dual-phase dedicated MDCT scan of the pancreas must be performed in patients in whom there is a strong clinical suspicion of a pancreatic lesion. To reduce radiation-related risks to the patient, a relatively low-radiation examination consisting of a single PVP contrast-enhanced CT examination, with a 5- to 7-mm slice thickness, is generally suficient for posttreatment follow-up. Potential role of DECT. As previously discussed, a small percentage of PDACs are not directly visualized on conventional SECT scans—even with optimized protocols—because of their size or the slight difference in attenuation between the tumor and adjacent pancreatic tissue.170 Dual energy is an evolving technique with several potential clinical applications in the abdomen, including detection of challenging pancreatic lesions.93,178 Moreover, DECT has potential for contrast media reduction through selection of low-energy images and radiation dose reduction through elimination of the noncontrast acquisition. A dual-phase pancreatic protocol (PP and PVP) is used on DECT scanners, similar to that on SECT. However, the PP acquisition is acquired in the DECT mode (140/80 kVp), and the PVP is acquired with SECT mode (120 kVp). Different studies have demonstrated higher contrast of PDAC at low x-ray energies (50-60 keV) and increased tumor conspicuity, allowing identiication of early-stage

B FIG 46-61 Adenocarcinoma of the pancreas. Axial contrast-enhanced pancreatic-phase MDCT (A) and curved reformatted MDCT (B) along the course of the main pancreatic duct display a hypodense mass in the body of the pancreas (arrows), with upstream dilatation of the main pancreatic duct (arrowheads).

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tumors not visualized on conventional CT.170,202 MD-I images improve depiction and characterization of hypoattenuating malignancies such as PDAC based on the difference of tissue iodine concentration (see Fig. 46-22). Iodine maps also improve the morphologic and enhancing characteristics of a pancreatic mass and show better delineation of lesion margins and deinition of the extension of the lesion. DECT can contribute to the staging of PDAC by improving evaluation of vascular compromise and distant metastasis. DECT allows more conident rule out of suspected pancreatic tumors. Role of MRI. MRI is usually considered a second-line imaging modality in patients with a high clinical suspicion of pancreatic tumor or in those with a suspected pancreatic mass and indeterminate indings on high-quality MDCT.173 The factors that limit MRI’s use as a irst-line tool for PDAC diagnosis and staging are related to motion and breathing artifacts in the case of poor patient cooperation, limited availability of the technique, and high costs. Currently MRI is mainly a problem-solving technique in patients with inconclusive MDCT studies. MRI can also be considered as an alternative in patients allergic to iodinated contrast agents, in patients with renal insuficiency, and in all cases in which reduced radiation exposure is required. In a recent study comparing state-of-the-art 16-detector MDCT and 1.5-T MRI, it was demonstrated that the sensitivity for detecting adenocarcinoma with MDCT alone, MDCT plus multiplanar reformations (MPR), and MRI alone was 83%, 96%, and 83%, respectively. In the same study, MRI had higher speciicity than MDCT alone (98% vs. 89%), but MDCT plus MPR performed similarly to MRI (97%).22,172 Owing to its inherent soft tissue contrast and high resolution, MRI including DWI can improve detection of subtle pancreatic lesions and small non–organ-deforming adenocarcinomas.105,189 On MRI, PDAC appears hypointense on nonenhanced T1-weighted images and, depending on the amount of associated desmoplastic response, demonstrates variable signal intensity on T2-weighted images. The surrounding normal parenchyma shows effacement of its lobular architecture. On dynamic imaging following IV administration of gadolinium contrast agent, PDAC enhances relatively less than the background pancreatic parenchyma in the early phase. It shows progressive enhancement in subsequent phases23 (Figs. 46-62 to 46-64). As with MDCT, the regional vascular anatomy can be mapped to assess for vascular involvement using 3D contrast-enhanced dynamic MR angiography. Moreover, 2D and 3D MRCP allows excellent visualization of the entire extrahepatic biliary tree and pancreatic duct. MRCP can demonstrate the typical double-duct pattern of obstruction, which is often seen with pancreatic or ampullary tumors.85 When MRCP is used in combination with a dynamic MRI examination of the pancreas, diagnostic preoperative ERCP can be avoided. MRI is particularly useful in detection and characterization of liver lesions and peritoneal implants, performing better than MDCT in this respect, especially in the setting of the small lesions.79,161 It has been demonstrated that peritoneal or hepatic metastases can be found at laparoscopy in 37% of patients with locoregional disease on CT.36 Secretin-enhanced MRCP can be performed as an integral part of the MRI examination. The increased duct distention improves MRCP quality and lesion conspicuity and allows more accurate assessment of pancreatic duct stenosis, helping to differentiate benign from malignant strictures. It can also enhance the diagnostic conidence.81,100,158,165,187 Because mass-forming chronic pancreatitis and pancreatic carcinoma share many morphologic characteristics on imaging studies, their differentiation is dificult with both CT and MRI. The “ductpenetrating” sign is considered highly speciic (96%) for differentiating the two. It is characterized by visualization of the main pancreatic duct, without ductal wall irregularities, within the pancreatic mass.267 A

main pancreatic duct with an irregular wall running through the mass is not considered predictive of a benign cause. In this setting, secretinenhanced MRCP (owing to secretin-induced distention of the pancreatic duct) may be useful in making the correct diagnosis. Role of hybrid PET CT. Although both MDCT and MRI provide excellent anatomic delineation of pathology of the pancreas, they are not always able to differentiate between malignant and benign disease.88,189 As a unique molecular and functional imaging technique, PET can complement structural modalities and overcome some of the deiciencies of structural imaging.5 PET performed with 18F FDG is increasingly being used for the diagnosis and staging of various cancers. The normal pancreas is not visualized on PET, so avid uptake in the pancreatic region is considered abnormal.137 An ongoing challenge in diagnostic radiology has been the accurate detection of pancreatic carcinoma and its differentiation from massforming pancreatitis with imaging methods.171 CT-guided ine-needle biopsy has been recommended for patients with ambiguous CT indings; however, even this technique has shortcomings owing to possible sampling errors.30 Accurate detection of lymph node metastases is also problematic because they are usually very small (10 mm in diameter indicates • Although cyst communication with pancreatic duct can also be increased likelihood of malignancy.107,221,273 seen with pseudocysts, IPMNs usually demonstrate a narrow neck Cysts >3 cm are also considered suspicious.240 at cyst-duct junction on imaging.222 Presence or absence of mural nodules or solid • Complications include obstructive pancreatitis or obstruction of components may be conirmed preoperatively by common bile duct with large lesions; malignant lesions in head EUS, which is superior to any other diagnostic may result in istulas with duodenum or common bile duct, modality in this regard. whereas those in body or tail may result in stomach or colonic Enhanced CT and dynamic MRI may be able to istulas.244 distinguish mural nodules or papillary neoplasms • Side-branch IPMNs have a low malignant potential; when such (≥3 mm) from mucin; nodules and neoplasms tumors can be clearly distinguished, treatment decisions should be enhance after contrast administration (see Fig. based on risk-beneit ratio, taking into account patient’s clinical 46-85). presentation, age, and surgical risk and size and morphologic IPMN can be invasive, including duodenal invasion, features of cyst.222,249 Asymptomatic side-branch IPMNs or those lymphadenopathy, peritoneal deposits, and liver without any suspicious features can be followed up without metastases.207 resection. If surgery is needed, a variety of function-preserving Malignancy is signiicantly higher in main-duct and minimal pancreatectomy techniques may be attempted.244 244,245 mixed IPMNs than in side-branch IPMNs. PET/ Mixed IPMN CT may be useful in increasing sensitivity of • Mixed-type IPMN is an advanced form of the side-branch type in detecting malignancy in mucinous lesions and can which the IPMN has spread to main pancreatic duct, or it is an complement anatomic details provided by CT (see ultimate form of main-duct type in which the IPMN involves Fig. 46-90). branch ducts as well (Fig. 46-89); it is not possible to establish the primary site of disease origin.207,244 • Biological behavior of mixed IPMN is similar to that of main-duct IPMN and should be dealt with surgically.

CHAPTER 46 Pancreas

*

1467

These malignant tumors are often older at presentation and have a male predilection; they are designated solid pseudopapillary carcinomas.134 The most common site for metastasis is the liver; metastases exhibit complex features similar to those of the primary tumor.42 Rarely lymph node metastasis, peritoneal spread, and multiplicity can occur.44 Invasion of the capsule and surrounding structures can occur.43,188 Benign SPT of the pancreas is treated with surgery, and complete resection is usually curative.124

Lymphangioma. Pancreatic lymphangiomas constitute less than 1%

FIG 46-91 Axial contrast-enhanced MDCT shows a well-encapsulated lesion with varying solid and cystic components due to degeneration in a solid pseudopapillary neoplasm. The enhancing solid areas are typically noted peripherally (arrows), whereas cystic spaces are usually more centrally located (asterisk).

Solid Pseudopapillary Tumors. Solid pseudopapillary tumor (SPT) is an uncommon benign exocrine pancreatic tumor commonly found in Asian or African American women between the second and third decades of life. These comprise about 9% of pancreatic cystic tumors. SPTs may be asymptomatic or they may present as a gradually enlarging nontender abdominal mass or with vague abdominal pain, discomfort, or obstructive symptoms.46 Pathologically these lesions are well encapsulated with varying amounts of necrosis, hemorrhage, and cystic changes. Both the capsule and intratumoral hemorrhage are important clues to the diagnosis because these features are rarely found in other pancreatic neoplasms.35 The classic CT features are a well-encapsulated lesion with varying solid and cystic components due to hemorrhagic degeneration.60 Following contrast administration, enhancing solid areas are typically noted peripherally, whereas cystic spaces are usually more centrally located (Fig. 46-91).120 MRI demonstrates a well-deined lesion with heterogeneous signal intensity on T1- and T2-weighted images, which relects the complex nature of the mass. T2-weighted images show a thick ibrous capsule, which is seen as a rim of low signal intensity. SPTs can be differentiated from islet cell tumors by the presence of a hemorrhagic component that has high signal intensity on T1-weighted images and low or inhomogeneous signal intensity on T2-weighted images; the cystic component of islet cell tumors has moderately increased signal intensity on T1- and T2-weighted images. Moreover the peripheral portion of SPTs does not demonstrate the hypervascularity typically seen in islet cell tumors.124,193 Nonfunctional islet cell tumors are found more often in older adults, and unlike SPTs they do not have female predominance. However, SPTs with a minimal cystic components or no intratumoral hemorrhage are dificult to differentiate from islet cell tumors.43 Smaller lesions are less sharply circumscribed, often appear unencapsulated, are less likely to show prominent cystic change, and often appear as solid tumors.132 Some lesions may have internal septa or calciications.124 Although the imaging features are informative, there is signiicant overlap with other lesions. Hence ine-needle aspiration biopsy, cytologic analysis, or excisional biopsy and histologic analysis are needed for deinitive diagnosis.33,124 Although most SPTs exhibit benign behavior, malignant degeneration, invasion of adjacent structures, and metastases can occur.46,142

of all lymphangiomas.50 These slow-growing tumors are generally considered to be of pancreatic origin if they are within the parenchyma, adjacent to the pancreas, or connected to the organ by a pedicle.186 There is a female preponderance, and all regions of the pancreas are equally affected.196 Most patients are asymptomatic, and the lesion is discovered incidentally on imaging studies.196 Others may present with vague abdominal pain, nausea, vomiting, palpable mass, or symptoms related to compression of neighboring organs.34 Occasionally acute presentations may be related to torsion of the pedicle, rupture, or hemorrhage into the lymphangioma.102 CT or MRI reveals a septated luid-density lesion and can assist in the preoperative evaluation by deining the exact anatomic location and content of the cyst196 (Fig. 46-92). Lymphangiomas are generally believed to be benign, so nonsurgical management may be reasonable if a deinitive diagnosis can be made.196 However, because the clinical and radiographic appearance of lymphangiomas overlaps the indings for other pancreatic tumors (e.g., mucinous cystic neoplasms, cystadenomas, teratomas), exploratory laparotomy with complete surgical excision (rather than marsupialization) may be necessary.50

Hemangioma. Pancreatic hemangioma may present as a palpable abdominal mass, GI bleeding, or a mass compressing adjacent structures such as the biliary tract or duodenum.37 The role of CT and MRI is similar to that for lymphangioma; however, MRI usually demonstrates more deinitive features of hemangioma, including a lobulated mass with moderately high signal intensity on T2-weighted images and marked enhancement after IV gadolinium administration.135,260 Enhancement may be delayed owing to sclerosis within the tumor.62 Histologically, hemangioma is easy to differentiate from lymphangioma, which has dilated lymphatic channels of varying sizes separated by thin septa.37

True Epithelial Cysts. True cysts of the pancreas differ from pseudocysts and retention cysts in terms of origin, histologic appearance, and clinical signiicance. True cysts are believed to develop anomalously from remnants of the embryologic ductal systems. Histologically they have a lining of epithelial cells that may atrophy owing to pressure. In such cases the wall may consist of smooth ibrous tissue. Rarely, true cysts are complicated by infection or hemorrhage. They may be detected incidentally and are commonly associated with von HippelLindau disease. CT and MRI features reveal a well-deined unilocular cystic lesion with indistinct walls.96,232

von Hippel-Lindau Disease. von Hippel-Lindau disease is a hereditary disease with a dominant trait. It is associated with a number of abnormalities, including angiomas of the central nervous system and eye and neoplasms and cysts of the pancreas, kidney, adrenal glands, and epididymis. Pancreatic involvement consists of cysts, serous cystadenomas, solid nonfunctional islet cell tumors, and adenocarcinomas; calciications are common (Figs. 46-93 and 46-94). Progression of the disease can result in steatorrhea and diabetes.44

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B

A

FIG 46-92 Axial contrast-enhanced MDCT (A) and the corresponding coronal reformatted image (B) reveal a well-deined irregular luid-density lesion (arrow) in relation to the body and tail of the pancreas, with subtle internal septations. This lesion was histopathologically conirmed to be lymphangioma. Cross-sectional imaging helps by deining the exact anatomic location and the content of the lesion preoperatively.

B

A

FIG 46-93 von Hippel-Lindau disease. A and B, Axial T2-weighted MRIs reveal lobulated cystic lesions (arrow) in the head, body, and tail of the pancreas, with multiple cysts in the kidneys bilaterally (arrowheads).

TRAUMA Acutely, pancreatic injuries may lead to death due to associated vascular involvement (portal vein, splenic vein, inferior vena cava); this is twice as likely with injuries to the pancreatic head versus the tail.270 Delayed morbidity and mortality are due to complications such as abscess, pseudocyst, istula, pancreatitis, hemorrhage, sepsis, and multiorgan failure. In addition, because surgical intervention can result in serious and prolonged postoperative complications, the decision to manage a pancreatic injury surgically must be weighed against the potential hazards of nonsurgical management.247 Isolated pancreatic injuries are rare; associated injuries, especially to the liver, stomach,

duodenum, and spleen, occur in more than 90% of cases. The pancreas is vulnerable to crush injury from blunt trauma due to its impact against the adjacent vertebral column. Two thirds of pancreatic injuries occur in the pancreatic body, and the remainder are equally distributed among the head, neck, and tail.156 In adults, more than 75% of blunt injuries to the pancreas are due to motor vehicle collisions; bicycle injuries in children and child abuse in infants may result in pancreatic injuries.106 CT is routinely used as a irst-line imaging study in acute trauma patients and can be helpful in deining injuries to the pancreas and associated complications.95 Direct signs of pancreatic injury include focal enlargement, laceration, and transection, which is seen as

CHAPTER 46 Pancreas

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F

FIG 46-96 Axial CT shows transection (arrow) of the pancreas in the FIG 46-94 Axial contrast-enhanced MDCT detects multiple cystic lesions (arrows) in the pancreas and left kidney in this case of von Hippel-Lindau disease.

region of the neck, resulting in decreased vascular enhancement and edema of the body and tail, with a difference in density compared with the head. A large amount of free luid (F) is also noted.

B

A

FIG 46-95 Pancreatic laceration. Axial (A) and coronal reformatted (B) MDCT images show focal enlargement and nonenhancing hypoattenuated areas (arrow) involving the head and uncinate process of the pancreas in this patient with abdominal injury.

hypoattenuating areas on CT; a fracture line may also be present (Figs. 46-95 and 46-96). Fluid collections such as hematomas, pseudocysts, and abscesses are often seen communicating with the pancreas at the site of fracture or transection (Figs. 46-97 and 46-98). Peripancreatic fat stranding, hemorrhage, and luid between the splenic vein and pancreas are useful secondary signs. Although CT does not always directly demonstrate the pancreatic duct, injury to the duct can be suggested by the degree of parenchymal injury95,270 (Table 46-16). MDCT is 91% sensitive and 91% speciic for pancreatic ductal injury.247

The prognosis of pancreatic injuries is related primarily to the integrity of the pancreatic duct; thus any patient with pancreatic injuries on CT and a high clinical index of suspicion for ductal injury should be considered for MRCP to allow direct imaging of the pancreatic duct.95 The associated parenchymal injuries can be evaluated using fat-suppressed T1- and T2-weighted images.95 If imaging of the pancreatic duct is not adequate or an injury is detected that might be amenable to stent placement, ERCP should be performed promptly95 (Figs. 46-99 and 46-100).

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A

B

C

D FIG 46-97 A and B, Axial contrast-enhanced MDCT (A) and axial T2-weighted MRI (B) show a small amount of luid (arrows in B) adjacent to the pancreatic head and neck in this patient with abdominal trauma. The fracture through the neck of the pancreas is well appreciated on MDCT (arrow in A), while MRI reveals duct discontinuity. C and D, ERCP conirms duct disruption with extravasation (arrow in C) and insertion of a therapeutic stent (arrow in D).

R

A

L

R

B FIG 46-98 Axial (A) and coronal curved reformatted (B) images reveal a chronic well-contained luid collection adjacent to the neck of the pancreas and communicating with the main pancreatic duct (arrow) in this patient with abdominal trauma.

L

CHAPTER 46 Pancreas CT Grading Scheme of Pancreatic Injury270 TABLE 46-16

Abdominal injury—suspected pancreatic trauma

CT—first line of investigation

Grade

Injury

A

Pancreatitis or supericial laceration (50% of pancreatic thickness) Transection of pancreatic tail Deep laceration of pancreatic head Transection of pancreatic head

B1 Parenchymal injury

Ductal injury

B2 C D

Further evaluation

MRCP

1471

ERCP

Imaging not adequate/ amenable to stent placement

FIG 46-99 Diagnostic approach to pancreatic trauma.

Pancreatic lesion/disease suspected clinically or on US

MDCT • Evaluation of lesion • CT angiography • CT pancreatography • Preoperative planning/staging • PET CT—preop evaluation/staging

Further evaluation If contraindicated

MR/MR pancreatography • Evaluation of lesion • Preferred for characterization/ duct communication • MR angiography • MR pancreatography • Preoperative planning/staging

Is diagnosis made? No

Yes

• EUS/CT guided aspiration or biopsy • Secretin-enhanced MRCP/ERCP

• Conservative • Surgery • ERCP • Observation

FIG 46-100 Imaging approach to pancreatic lesions.

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TABLE 46-17 Metabolic Disorder

CT and MR Imaging of the Whole Body

Iniltrative, Metabolic, and Other Disorders

Clinical/Pathologic

Imaging Appearance

Hemocromatosis

Results from excessive accumulation of iron in the body. The disease has a primary idiopathic form, resulting from excessive absorption of iron, and a secondary form, resulting from excessive accumulation of iron from multiple transfusions.63

CT shows an increased density in the pancreas and adjacent peripancreatic lymph nodes, although no correlation has been found between that density and pancreatic dysfunction or insuficiency.1152 Unopaciied vessels may give the spurious impression of low-density masses in the pancreas, but this can be clariied by contrast studies. MRI reveals low signal intensity in the pancreas and other organs (liver, spleen) on T2-weighted GRE images, spin echo images being less sensitive.96

Cystic Fibrosis

Life-threatening autosomal recessive disease, results in exocrine pancreatic insuficiency in the majority of patients; only 10% to 15% of patients with cystic ibrosis retain suficient pancreatic function to prevent steatorrhea.71 Although the course and prognosis of the disease are determined mainly by the progression of pulmonary disease, pancreatic insuficiency may result in earlier colonization of the airway by Pseudomonas aeruginosa.71 Exocrine pancreatic insuficiency may not become clinically apparent until 98% to 99% of the parenchyma undergoes destruction.250 Before total or near-total fatty replacement of the pancreas occurs, there is no correlation between histologic indings and the results of pancreatic function tests. The degree of fatty replacement of the pancreas and atrophy is related to the severity of expression of cystic ibrosis.71,200,250

CT is highly sensitive for depicting fatty replacement (Fig. 46-95). The pancreas has an inhomogeneous appearance on CT, with fatty changes, tiny calciication, and areas of lower attenuation representing cysts.51 Complete fatty replacement of the pancreas represents a late phenomenon and is often seen in older patients; despite diffuse fatty changes, the shape of the pancreas is maintained.51 MRI can show partial fatty replacement of the pancreas with focal areas of sparing; a lobulated, enlarged pancreas that appears hyperintense on T1- and T2-weighted images owing to nearly complete lipomatous replacement (lipomatous pseudohypertrophy); an atrophied fatty pancreas with variable degrees of ibrofatty replacement, seen as a small pancreas with inhomogeneous signal intensity; an atrophied pancreas without fatty replacement; and pancreatic cystosis, which relects cyst formation due to inspissated secretions.71,72,169,183,250 In addition, the quantitative assessment of reduced T1 values secondary to fatty iniltration improves the overall sensitivity of MRI for the early diagnosis of fatty degeneration of the pancreas and hence allows the earlier detection of pancreatic compromise, before it is visually apparent on imaging.71 The main disadvantage of MRI is the inability to show calciication.250

Fatty

Pancreatic lipomatosis or fatty replacement of the pancreas is a rare benign disease. Fatty replacement may present as reticular patches or multiple tiny nodules throughout the pancreas; sometimes it presents as a focal fatty mass that may resemble a pancreatic neoplasm (Fig. 46-96).111,168 It is associated with a variety of diseases, including obesity, diabetes mellitus, chronic pancreatitis, hereditary pancreatitis, obstruction of the pancreatic duct by calculus or tumor, and cystic ibrosis.202

The involved gland appears hypodense on CT. A mild degree of focal fatty replacement may not be diagnosed with CT alone. Moreover, contrastenhanced CT cannot show the negative attenuation value of mild fatty replacement because normal pancreatic parenchyma trapped between fatty areas exhibits contrast enhancement. Also, a focal fatty mass may be mistaken for a true pancreatic neoplasm on CT.128 MRI may be helpful in conirming the presence of focal fatty replacement of the pancreas, especially opposed-phase chemical-shift MR images that reveal a reduction in signal intensity.113,128

Heterotopic

Heterotopic pancreas is deined as pancreatic tissue that lacks anatomic and vascular continuity with the main body of the pancreas.59 The heterotopic pancreatic tissue has all the normal pancreatic elements, including pancreatic acini, pancreatic ducts, and islets of Langerhans, at histologic examination. Most often, heterotopic pancreas is found in the stomach, duodenum, or upper part of the jejunum, although it may be found at several other locations.127

Heterotopic pancreas on upper gastrointestinal examination consist of a small, sharply marginated, round or oval, broad-based submucosal mass lesion that may extend into the muscularis and serosa, similar to any other gastrointestinal tumor; thus, it may be dificult to differentiate it from other submucosal lesions on imaging.41,127 Endoscopic biopsy should be performed before surgical resection, and a more conservative, nonsurgical approach should be considered in asymptomatic patients.41 Occasionally, complications such as pancreatitis, pseudocyst, cyst formation, insulinoma, adenoma, and malignant transformation can occur.45,59,127,255

CHAPTER 46

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221. Sahani DV, Kadavigere R, Blake M, et al: Intraductal papillary mucinous neoplasm of pancreas: Multi-detector row CT with 2D curved reformations—Correlation with MRCP. Radiology 238(2):560– 569, 2006. 222. Sahani DV, Kadavigere R, Saokar A, et al: Cystic pancreatic lesions: A simple imaging-based classiication system for guiding management. Radiographics 25(6):1471–1484, 2005. 223. Sahani DV, Kalva SP, Farrell J, et al: Autoimmune pancreatitis: Imaging features. Radiology 233(2):345–352, 2004. 224. Saif MW: Primary pancreatic lymphomas. JOP 7(3):262–273, 2006. 225. Sarr MG, Murr M, Smyrk TC, et al: Primary cystic neoplasms of the pancreas. Neoplastic disorders of emerging importance—Current state-of-the-art and unanswered questions. J Gastrointest Surg 7(3):417–428, 2003. 226. Schima W, Fugger R, Schober E, et al: Diagnosis and staging of pancreatic cancer: Comparison of mangafodipir trisodium-enhanced MR imaging and contrast-enhanced helical hydro-CT. AJR Am J Roentgenol 179(3):717–724, 2002. 227. Schnedl WJ, Reisinger EC, Schreiber F, et al: Complete and partial agenesis of the dorsal pancreas within one family. Gastrointest Endosc 42(5):485–487, 1995. 228. Schueller G, Schima W, Schueller-Weidekamm C, et al: Multidetector CT of pancreas: Effects of contrast material low rate and individualized scan delay on enhancement of pancreas and tumor contrast. Radiology 241(2):441–448, 2006. 229. Semelka RC, Ascher SM: MR imaging of the pancreas. Radiology 188(3):593–602, 1993. 230. Semelka RC, Custodio CM, Cem Balci N, et al: Neuroendocrine tumors of the pancreas: Spectrum of appearances on MRI. J Magn Reson Imaging 11(2):141–148, 2000. 231. Sheehan MK, Beck K, Pickleman J, et al: Spectrum of cystic neoplasms of the pancreas and their surgical management. Arch Surg 138(6):657– 660, discussion 660–662, 2003. 232. Shirkhoda A, Mittelstaedt CA: Demonstration of pancreatic cysts in adult polycystic disease by computed tomography and ultrasound. AJR Am J Roentgenol 131(6):1074–1076, 1978. 233. Shultz S, Druy EM, Friedman AC: Common hepatic artery aneurysm: Pseudopseudocyst of the pancreas. AJR Am J Roentgenol 144(6):1287– 1288, 1985. 234. Siegelman SS, Copeland BE, Saba GP, et al: CT of luid collections associated with pancreatitis. AJR Am J Roentgenol 134(6):1121–1132, 1980. 235. Singer MV, Gyr K, Sarles H: Revised classiication of pancreatitis. Report of the Second International Symposium on the Classiication of Pancreatitis in Marseille, France, March 28-30, 1984. Gastroenterology 89(3):683–685, 1985. 236. Soriano A, Castells A, Ayuso C, et al: Preoperative staging and tumor resectability assessment of pancreatic cancer: Prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging, and angiography. Am J Gastroenterol 99(3):492–501, 2004. 237. Stollfuss JC, Glatting G, Friess H, et al: 2-(luorine-18)-luoro-2-deoxyD-glucose PET in detection of pancreatic cancer: Value of quantitative image interpretation. Radiology 195(2):339–344, 1995. 238. Stolte M, Weiss W, Volkholz H, et al: A special form of segmental pancreatitis: Groove pancreatitis. Hepatogastroenterology 29(5):198–208, 1982. 239. Suda K, Shiotsu H, Nakamura T, et al: Pancreatic ibrosis in patients with chronic alcohol abuse: Correlation with alcoholic pancreatitis. Am J Gastroenterol 89(11):2060–2062, 1994. 240. Sugiyama M, Atomi Y, Kuroda A: Two types of mucin-producing cystic tumors of the pancreas: Diagnosis and treatment. Surgery 122(3):617– 625, 1997. 241. Sugiyama M, Haradome H, Atomi Y: Magnetic resonance imaging for diagnosing chronic pancreatitis. J Gastroenterol 42(Suppl 17):108–112, 2007.

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242. Tamm EP, Silverman PM, Charnsangavej C, et al: Diagnosis, staging, and surveillance of pancreatic cancer. AJR Am J Roentgenol 180(5):1311–1323, 2003. 243. Tamura R, Ishibashi T, Takahashi S: Chronic pancreatitis: MRCP versus ERCP for quantitative caliber measurement and qualitative evaluation. Radiology 238(3):920–928, 2006. 244. Tanaka M: Intraductal papillary mucinous neoplasm of the pancreas: Diagnosis and treatment. Pancreas 28(3):282–288, 2004. 245. Taouli B, Vilgrain V, Vullierme MP, et al: Intraductal papillary mucinous tumors of the pancreas: Helical CT with histopathologic correlation. Radiology 217(3):757–764, 2000. 246. Tatli S, Mortele KJ, Levy AD, et al: CT and MRI features of pure acinar cell carcinoma of the pancreas in adults. AJR Am J Roentgenol 184(2):511–519, 2005. 247. Teh SH, Sheppard BC, Mullins RJ, et al: Diagnosis and management of blunt pancreatic ductal injury in the era of high-resolution computed axial tomography. Am J Surg 193(5):641–643, discussion 643, 2007. 248. Tempero MA, Arnoletti JP, Behrman S, et al: Pancreatic adenocarcinoma. J Natl Compr Canc Netw 8(9):972–1017, 2010. 249. Terris B, Ponsot P, Paye F, et al: Intraductal papillary mucinous tumors of the pancreas conined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 24(10):1372–1377, 2000. 250. Tham RT, Heyerman HG, Falke TH, et al: Cystic ibrosis: MR imaging of the pancreas. Radiology 179(1):183–186, 1991. 251. Thoeni RF: The revised Atlanta classiication of acute pancreatitis: Its importance for the radiologist and its effect on treatment. Radiology 262(3):751–764, 2012. 252. Tublin ME, Tessler FN, Cheng SL, et al: Effect of injection rate of contrast medium on pancreatic and hepatic helical CT. Radiology 210(1):97–101, 1999. 253. Tunaci M: Multidetector row CT of the pancreas. Eur J Radiol 52(1):18–30, 2004. 254. Turner MA: The role of US and CT in pancreatitis. Gastrointest Endosc 56(6 Suppl):S241–S245, 2002. 255. Ura H, Denno R, Hirata K, et al: Carcinoma arising from ectopic pancreas in the stomach: Endosonographic detection of malignant change. J Clin Ultrasound 26(5):265–268, 1998. 256. vanSonnenberg E, Wittich GR, Casola G, et al: Percutaneous drainage of infected and noninfected pancreatic pseudocysts: Experience in 101 cases. Radiology 170(3 Pt 1):757–761, 1989. 257. Varadarajulu S, Wallace MB: Applications of endoscopic ultrasonography in pancreatic cancer. Cancer Control 11(1):15–22, 2004. 258. Varadhachary GR, Tamm EP, Abbruzzese JL, et al: Borderline resectable pancreatic cancer: Deinitions, management, and role of preoperative therapy. Ann Surg Oncol 13(8):1035–1046, 2006. 259. Vargas R, Nino-Murcia M, Trueblood W, et al: MDCT in pancreatic adenocarcinoma: Prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR Am J Roentgenol 182(2):419–425, 2004. 260. Vogel AM, Alesbury JM, Fox VL, et al: Complex pancreatic vascular anomalies in children. J Pediatr Surg 41(3):473–478, 2006. 261. Volmar KE, Vollmer RT, Jowell PS, et al: Pancreatic FNA in 1000 cases: A comparison of imaging modalities. Gastrointest Endosc 61(7):854– 861, 2005. 262. von Schulthess GK, Steinert HC, Hany TF: Integrated PET/CT: Current applications and future directions. Radiology 238(2):405–422, 2006.

263. Vujic I: Vascular complications of pancreatitis. Radiol Clin North Am 27(1):81–91, 1989. 264. Warshaw AL, Compton CC, Lewandrowski K, et al: Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg 212(4):432–443, discussion 444–445, 1990. 265. Warshaw AL, Fernandez-del Castillo C: Pancreatic carcinoma. N Engl J Med 326(7):455–465, 1992. 266. Warshaw AL, Rattner DW, Fernandez-del Castillo C, et al: Middle segment pancreatectomy: A novel technique for conserving pancreatic tissue. Arch Surg 133(3):327–331, 1998. 267. Wiersema MJ: Accuracy of endoscopic ultrasound in diagnosing and staging pancreatic carcinoma. Pancreatology 1(6):625–632, 2001. 268. Williams DB, Sahai AV, Aabakken L, et al: Endoscopic ultrasound guided ine needle aspiration biopsy: A large single centre experience. Gut 44(5):720–726, 1999. 269. Winston CB, Mitchell DG, Outwater EK, et al: Pancreatic signal intensity on T1-weighted fat saturation MR images: Clinical correlation. J Magn Reson Imaging 5(3):267–271, 1995. 270. Wong YC, Wang LJ, Lin BC, et al: CT grading of blunt pancreatic injuries: Prediction of ductal disruption and surgical correlation. J Comput Assist Tomogr 21(2):246–250, 1997. 271. Yamada T, Alpers D, Kountz WB, et al: Textbook of gastroenterology, Philadelphia, 2003, Lippincott Williams & Wilkins. 272. Yamada Y, Mori H, Kiyosue H, et al: CT assessment of the inferior peripancreatic veins: Clinical signiicance. AJR Am J Roentgenol 174(3):677–684, 2000. 273. Yamaguchi K, Ogawa Y, Chijiiwa K, et al: Mucin-hypersecreting tumors of the pancreas: Assessing the grade of malignancy preoperatively. Am J Surg 171(4):427–431, 1996. 274. Yamaguchi K, Tanaka M: Groove pancreatitis masquerading as pancreatic carcinoma. Am J Surg 163(3):312–316, discussion 317–318, 1992. 275. Yeo TP: Demographics, epidemiology, and inheritance of pancreatic ductal adenocarcinoma. Semin Oncol 42(1):8–18, 2015. 276. Yeo CJ, Bastidas JA, Lynch-Nyhan A, et al: The natural history of pancreatic pseudocysts documented by computed tomography. Surg Gynecol Obstet 170(5):411–417, 1990. 277. Yogi Y, Shibue T, Hashimoto S: Annular pancreas detected in adults, diagnosed by endoscopic retrograde cholangiopancreatography: Report of four cases. Gastroenterol Jpn 22(1):92–99, 1987. 278. Yokoyama T, Miyagawa S, Noike T, et al: Isolated pancreatic tuberculosis. Hepatogastroenterology 46(27):2011–2014, 1999. 279. Yu J, Turner MA, Fulcher AS, et al: Congenital anomalies and normal variants of the pancreaticobiliary tract and the pancreas in adults: Part 2, Pancreatic duct and pancreas. AJR Am J Roentgenol 187(6):1544– 1553, 2006. 280. Zamboni G, Luttges J, Capelli P, et al: Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: A study on 53 resection specimens and 9 biopsy specimens. Virchows Arch 445(6):552–563, 2004. 281. Zhang L, Chari S, Smyrk TC, et al: Autoimmune pancreatitis (AIP) type 1 and type 2: An international consensus study on histopathologic diagnostic criteria. Pancreas 40(8):1172–1179, 2011. 282. Zhang XM, Shi H, Parker L, et al: Suspected early or mild chronic pancreatitis: Enhancement patterns on gadolinium chelate dynamic MRI. Magnetic resonance imaging. J Magn Reson Imaging 17(1):86–94, 2003.

47 Mesentery Yong Ho Auh, George Shih, Jung Hoon Kim, and Stuart Bentley-Hibbert

EMBRYOLOGY

ANATOMY

At the end of the third week of gestation, the primitive gastrointestinal (GI) tract of an embryo consists of a straight tube suspended from the esophagus to the rectum by the dorsal mesentery, which contains the vascular supply. In the dorsal mesentery, the portion connected to the stomach is known as the dorsal mesogastrium. As the embryo lengthens, the caudal portion of the septum transversum thins and becomes the ventral mesentery. It attaches the stomach and duodenum to the ventral wall of the abdominal cavity.97 Because there is no ventral mesentery below the foregut, the ventral mesentery is the same as the ventral mesogastrium. The sagittally oriented ventral and dorsal mesogastrium, along with the upper GI tract, divide the upper abdominal cavity into equally sized right and left peritoneal cavities. During the fourth gestational week, cords of tissue within the ventral mesogastrium begin to grow rapidly, forming the liver, bile ducts, and ventral pancreas within the ventral mesogastrium, while the spleen and dorsal pancreas arise within the dorsal mesogastrium. The remainder of the mesogastrium become the ligaments and omenta. The anterior part of the ventral mesogastrium between the anterior abdominal wall and the liver becomes the falciform ligament, and the posterior part between the liver and the stomach becomes the lesser omentum. The posterior portion of the dorsal mesogastrium between the spleen and posterior abdominal wall becomes the splenorenal ligament, while the anterior portion between the spleen and the stomach becomes the gastrosplenic ligament, which is a part of the greater omentum. The stomach initially develops as a fusiform bulge in the foregut. This bulge rapidly becomes asymmetric owing to the more rapid growth of its dorsal margin (greater curvature) than of its ventral margin (lesser curvature). The stomach then undergoes a 90-degree counterclockwise rotation along with the ventral and dorsal mesogastrium (Fig. 47-1). The dorsal mesentery inferior to the stomach evolves into small bowel mesentery that attaches the jejunum and ileum to the posterior abdominal wall and mesocolon in the transverse and sigmoid colon. The dorsal mesentery of the duodenum, along with the pancreas, is fused with the posterior abdominal wall and loses its mesentery. Rarely when they are not completely fused with the posterior abdominal wall, the duodenum and pancreas can become intraperitonealized (Fig. 47-2). The dorsal mesentery attached to ascending and descending colon and rectum is lost once these segments of colon are fused with the posterior abdominal and pelvic walls. Not infrequently the ascending and descending colon are incompletely fused with the posterior abdominal wall and become intraperitonealized (Fig. 47-3).3,4,21 Incomplete fusion with the posterior pelvic wall can cause the rectum to be intraperitonealized (Fig. 47-4).

In its broad meaning, mesentery may include any membranous derivatives of the embryonic dorsal and ventral mesentery (e.g., falciform ligament, lesser omentum, gastrosplenic and splenorenal ligaments).8 When it is deined as a membranous fold attached to various organs, its deinition can be even broader and may include even the broad ligament of the uterus, mesosalpinx, gastropancreatic fold, and other structures. The usual deinition of the mesentery is, however, limited to the derivatives of the embryonic dorsal mesentery below the foregut—the membranous fold connecting the small and large bowel to the posterior body wall. Mesenteries are double-layered folds of peritoneum within which lie continuations of the subperitoneal space,26,92,102 which contains various amounts of adipose tissue within which the arteries, veins, lymphatics, and nerves of the bowel course. On normal cross-sectional images, although the supplying and draining vessels can be traced to and from the major mesenteric vessels, the actual leaves of the mesentery are not discernible unless they are separated by intervening ascites or peritoneal thickening (Fig. 47-5). Mesenteries can act as barriers as well as conduits for the spread of intraperitoneal and extraperitoneal diseases.92

Small Bowel Mesentery The narrowest deinition of the mesentery is the small bowel mesentery, also known as the mesentery proper or mesenterium. The small bowel mesentery is a broad fan-shaped fold of peritoneum connecting the jejunum and ileum to the root of the mesentery. The mesenteric root is approximately 15 cm long and is directed obliquely downward to the right from the duodenojejunal lexure to the ileocecal junction. The intestinal border of the mesentery is about 6 m long and is formed into numerous pleats. The mesentery consists of two layers of the peritoneum between which lie the jejunal and ileal branches of the superior mesenteric artery (SMA), with accompanying veins, nerve plexuses, lymphatics, lymph nodes, connective tissue, and fat (Fig. 47-6). The gastrocolic trunk is an anatomic landmark between the transverse mesocolon and root of the small bowel mesentery. On computed tomography (CT) and magnetic resonance imaging (MRI), the mesentery appears as a fat-containing structure inseparable from the other fat-containing peritoneal folds (e.g., greater omentum) or even from retroperitoneal fat (see Fig. 47-5). Normal mesenteric fat is similar in density to subcutaneous fat (−100 to −160 Hounsield units [HU]) on CT125 and has the same signal intensity on MRI. The jejunal and ileal vessels can be identiied as distinct round or linear densities within the mesenteric fat. Normal-sized lymph nodes within Text continued on p. 1484

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FIG 47-1 Schematic drawing of early fetal development of the mesentery. A, During the fourth week of embryonal life, cords of tissue from the ventral and dorsal mesogastrium grow rapidly, forming the liver and ventral pancreas within the ventral mesogastrium, while the spleen and the dorsal pancreas develop within the dorsal mesogastrium. The primitive foregut is suspended within the abdomen by the ventral and dorsal mesogastrium along with cords of tissue that divide the cavity into symmetric right and left halves. B, During early fetal life the dorsal margin of the stomach bulges rapidly along with rapid growth of the dorsal mesogastrium, forming a large greater omentum. Meanwhile the dorsal pancreas fuses to the posterior abdominal wall (dashed lines). a, falciform ligament; b, gastrohepatic ligament; c, gastrosplenic ligament; d, lienorenal ligament.

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D FIG 47-2 Incomplete fusion of the pancreas and duodenum to posterior abdominal wall. A to D, Four consecutive axial CT images of the abdomen at the level of the transverse portion of the duodenum (arrows) show anterior displacement of the transverse duodenum and uncinate process of the pancreas (black and white arrows) by a jejunal loop (asterisk).

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A B

C FIG 47-3 Colocolic intussusception of descending colon. Two consecutive coronal reformatted CT images (A and B) and one axial CT image (C) show a bowel-within-bowel appearance (black arrows) in the descending colon. Descending mesocolon is seen as a curvilinear fat density (white arrow) as part of the intussusceptum.

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B FIG 47-4 Peritonealized rectum by mesorectum. A and B, Two consecutive axial CTs of the pelvis show ascites in bilateral pararectal fossae (white arrows) that extends behind the rectum, demarcating the fatcontaining mesorectum (black arrow).

A

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C FIG 47-5 Small bowel mesentery in a normal subject (A) and a patient with ascites (B and C). A, Normally the mesentery is not identiied as individual pleats. Mesenteric fat is inseparable from retroperitoneal and omental fat. It can be indirectly traced and identiied by the undulating vessels (arrows). B and C, Once there is enough ascites, each pleat of mesentery can be separately identiied. A long thin mesenteric attachment to the root of the mesentery (arrows in B) is well depicted. The mesentery can be easily traced and identiied by the mesenteric vessels on coronal reformatted CT (arrows in C).

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D FIG 47-6 Peritoneal lymphomatosis. A to C, Axial CT of abdomen and pelvis and (D) coronal reformatted CT show omental caking (arrow) and masslike lymphoma implantation onto pleats of mesentery (arrowheads in D). A long thick mesenteric attachment to the root of the mesentery (arrows in D) is well depicted.

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FIG 47-7 Normal anatomy of mesenteric vessels and lymph nodes. Contrast-enhanced fat-saturated coronal MRI shows enhanced branches of the SMV (large arrows) and SMA (small arrows). Arteries are smaller and run parallel to veins. Along with these vessels, normal mesenteric nodes (arrowheads) are scattered as round or ovoid structures.

the mesentery are routinely identiied, particularly following contrast enhancement and in coronal images100 (Fig. 47-7).

Mesocolon The mesocolon is composed of two layers of peritoneum that connect the colon to the posterior abdominal wall; it contains its related blood vessels, lymphatics, nerves, and a variable amount of adipose tissue. The transverse colon and sigmoid colon have a well-formed mesocolon. The cecum is attached to the ileum by the ileocecal fold and has a complete peritoneal covering with no mesocolon in most cases.49 On CT and MRI, the mesocolon is not usually easily discernable, but it can be traced by identifying its blood vessels from the marginal vessels to the superior or inferior mesenteric vessel or vice versa18 (Fig. 47-8). The transverse mesocolon is a broad fold connecting the transverse colon to the posterior abdominal wall.88 The transverse mesocolon is typically absent close to the hepatic lexure, and therefore the colon is usually in direct posterior contact with the second portion of the duodenum as it crosses. The mesocolon is short over the irst part of the head of the pancreas but is much longer where it is attached to the anterior border of the body of the pancreas.49,138 It ends at the splenic lexure but usually extends farther laterally as a peritoneal fold called the phrenicocolic ligament.87 Because of its intimate relationship with almost the entire length of the pancreas, pancreatitis easily extends to the transverse mesocolon135 (Fig. 47-9). The transverse mesocolon is formed by two layers of peritoneum; the upper layer is adherent to but separable from the greater omentum138 (Fig. 47-10). Between the two layers of the transverse mesocolon are the middle colic arteries and veins, lymphatics, and nerves of the transverse mesocolon. Because of the transverse mesocolon, the transverse colon has a great deal of mobility, and the position and orientation of vessels in the transverse mesocolon vary depending upon the position of the transverse colon.18 The sigmoid mesocolon is a fold of peritoneum that attaches the sigmoid colon to the posterior pelvic wall. Its line of attachment is

Omentum The omentum is a fold of peritoneum extending from the stomach to adjacent organs. Different from the small bowel mesentery and mesocolon, which connect the bowels to the posterior abdominal wall, the omentum connects two interperitoneal organs: the lesser omentum (between the stomach and liver) and the greater omentum (between the stomach and spleen or transverse colon). Like the small bowel mesentery and mesocolon, the greater omentum is formed by two layers of peritoneum within which lie vessels, lymphatics, lymph nodes, nerves, and varying amounts of adipose tissue127,143 (Fig. 47-12; see Fig. 47-10). The lesser omentum extends from the lesser curvature of the stomach and irst portion of the duodenum to the liver at the porta hepatis into the issure for the ligamentum venosum.3,92 The portion of the lesser omentum extending between the liver and stomach is called the gastrohepatic ligament, and that between the liver and duodenum, the hepatoduodenal ligament. The left gastric artery acts a marker for the gastrohepatic ligament, and the hepatic artery proper acts as an anatomic marker for the hepatoduodenal ligament. At its right free margin, the lesser omentum encloses the portal triad with its lymphatics and lymph nodes; this free margin is the anterior edge of the epiploic foramen.144 The lesser omentum contains the left and right gastric arteries and corresponding veins as well as lymphatics and lymph nodes.136 When there is suficient ascites, it may appear as an undulating fat-containing plate in the issure for the ligamentum venosum and serve as an anatomic landmark separating the lesser sac from the greater sac3 (Fig. 47-13). The left gastric vessels are easily identiied at the lesser curvature aspect of the lesser omentum. Normal lymph nodes up to 8 mm in diameter are also frequently seen in the lesser omentum. The dilated coronary vein can easily be visualized in patients with portal hypertension.9 The greater omentum is the largest peritoneal fold, consisting of a double sheet folded on itself so that it is made of four layers in early development. The inner two layers are fused below the transverse colon and lose their mesothelial lining during fetal life (see Fig. 47-10). This fusion limits the inferior extent of the lesser sac. It stretches from the greater curvature of the stomach and irst portion of the duodenum downward in front of the small intestine for a variable distance. It adheres to but is separable from the upper layer of the transverse mesocolon. The gastrocolic ligament is the part of the greater omentum Text continued on p. 1489

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FIG 47-8 Sigmoid colon cancer. A to D, Coronal reformatted CT shows focal enhanced wall thickening in the upper rectum (arrowheads) with iniltration surrounding the sigmoid mesocolon. Small lymph node is noted on the sigmoid mesocolon (black arrow). The sigmoid mesocolon can be easily traced on coronal reformatted CT (arrows).

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D FIG 47-9 Acute pancreatitis. A, CT scout image shows sharply demarcated absence of colonic air (arrows) at midsegment of the transverse colon owing to involvement of pancreatitis through the transverse mesocolon. B to D, Three consecutive axial CT images show a large phlegmonous inlammatory mass (asterisk) encircling a segment of transverse colon (arrows in D), which extends from the pancreas.

CHAPTER 47

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e

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a Sto m

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Pancreas 3rd portion duodenum a

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B FIG 47-10 Schematic drawing of posterior attachment of small bowel mesentery, transverse and sigmoid mesocolon, and greater omentum. Coronal (A) and sagittal (B) views show the attachment of greater omentum and transverse mesocolon running parallel to each other—the greater omentum being shorter and superior to the mesocolon. These two peritoneal folds are loosely attached but not fused. Note the inverted V–shaped attachment of the sigmoid mesocolon. a, greater omentum; b, transverse mesocolon; c, small bowel mesentery; d, sigmoid mesocolon; e, gastrosplenic ligament.

A

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FIG 47-11 Sigmoid volvulus. A to D, Coronal reformatted CT shows distended sigmoid loop with inverted-U coniguration and coffee bean sign (arrows). There is a whirlpool sign with torsion of the sigmoid vessels (arrowheads). A transition point with abrupt reduction in bowel caliber is seen. Continued

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D FIG 47-11, cont’d

a c b

d e

FIG 47-13 Lesser omentum. Axial CT shows the lesser omentum (black arrows) as a thin line in the issure for the ligamentum venosum, extending from the lesser curvature of the stomach to the umbilical portion of the left portal vein (open arrow).

FIG 47-12 Schematic drawing of lesser omentum and greater omentum. Lesser omentum extends from lesser curvature of the stomach and superior border of the irst portion of the duodenum to the liver into the issure for the ligamentum venosum. Greater omentum drapes down from the greater curvature of the stomach and inferior border of the irst portion of the duodenum, covering transverse colon and small bowel. Superior portion of the greater omentum extends to hilum of the spleen and becomes gastrosplenic ligament. a, gastrohepatic ligament; b, hepatoduodenal ligament; c, gastrosplenic ligament; d, gastrocolic ligament; e, duodenocolic ligament.

CHAPTER 47 stretching from the stomach to the transverse colon, where as the duodenocolic ligament it extends from the irst portion of the duodenum to the transverse colon (see Fig. 47-12).116 The gastrosplenic ligament connects the stomach to the spleen and is the part of the greater omentum. Contained within the greater omentum are the gastroepiploic arteries and veins. On cross-sectional images the greater omentum appears as a thin, broad, fat-containing area just beneath the anterior abdominal wall and ventral to the stomach, transverse colon, and small bowel loops.127 The greater omentum is frequently found wrapped about the organs in the upper part of the abdomen—only occasionally is it evenly dependent anterior to the intestines. Especially in the presence of a large amount of ascites, it is wrapped on itself and often misplaced at a particular area. It may limit the spread of infection by forming adhesions with areas of inlammation in the peritoneal cavity. It is frequently involved by peritoneal diseases, either infective or malignant.

RADIOLOGIC MANIFESTATIONS OF MESENTERIC DISEASE Mesenteric disease is dificult to separate from peritoneal or bowel disease, because the mesentery is intimately related to the peritoneum

A

Mesentery

and bowel anatomically and physiologically. Therefore primary peritoneal and bowel diseases often accompany changes of the mesentery and vice versa.89,91 The peritoneum is indeed a mesenteric component because it is the lining membrane of the mesentery. Peritonitis, particularly tuberculous peritonitis, and peritoneal carcinomatosis cause or are associated with mesenteric abnormality. By the same token, primary mesenteric disease processes cause and are associated with abnormal peritoneal indings like thickening and enhancement of peritoneal membrane or ascites or changes of bowel (Figs. 47-14 and 47-15). Inlammatory, infectious, and neoplastic diseases of bowel bring mesenteric fat changes and regional lymphadenopathy. Sclerosing mesenteritis induces, on the other hand, thickening and edema of bowel wall and ascites secondary to vascular and/or lymphatic involvement (see Fig. 47-14). Because mesenteric space is continuous with extraperitoneal space as subperitoneal space, it becomes a conduit transmitting disease processes arising in the retroperitoneal space to GI organs and vice versa.102,130 Whether abnormal mesenteric changes are due to primary mesenteric causes or are secondary effects due to disease processes of neighboring organs or structures, they manifest distinct and limited radiologic indings. These indings come together in different combinations or independently.

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D FIG 47-14 Sclerosing mesenteritis in a 70-year-old man. A and B, Noncontrast axial CT images show a well-circumscribed soft tissue mass (white arrows) in the small bowel mesentery, with coarse calciication (black arrow). C and D, On corresponding postcontrast images at the same level the mass encases the mesenteric vessels, causing vessel engorgement in the leaves of the mesentery and ascites (a). The superior mesenteric artery (black arrowhead in C) is encased by the soft tissue mass. (Courtesy Dr. Ha, Asan Medical Center, Seoul, Korea.)

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Mesenteric mass, either cystic or solid, is quite uncommon. Other than conglomerated massive lymphadenopathy of lymphoma and mesenteric involvement of carcinoid tumor, a solid mesenteric mass is rare. Even though carcinoid tumor arises primarily from bowel— most frequently from ileum—it is often dificult to recognize the primary bowel mass. Instead the spiculated or stellate mesenteric mass is the dominant inding, which is a distinctive form of sclerosing mesenteritis due to the tissue reaction to released hormones by the tumor121 (see Fig. 47-20). Primary mesenteric GIST (GI stromal tumor)64 (Fig. 47-26), desmoid tumor associated with or without familial adenomatous polyposis73 (Fig. 47-27), and inlammatory pseudotumor92 (see Fig. 47-15) are known entities. Other benign and malignant primary mesenchymal tumors or metastatic tumors are extremely rare58 (Fig. 47-28). Also rare are cystic mesenteric lesions, commonly called mesenteric or omental cysts, which is rather descriptive terminology. A variety of different pathologic entities comprise such entities. Most common is lymphangioma (Figs. 47-29 and 47-30). Other types include enteric cyst, enteric duplication cyst, mesothelial cyst, nonpancreatic pseudocyst, cystic mesothelioma, and cystic teratoma.128

Lymphadenopathy B FIG 47-15 Inlammatory pseudotumor. Axial (A) and coronal (B) reformatted CT of the lower abdomen show spiculated soft tissue mass (arrows) in the mesentery. Mesenteric vessels (arrowhead in B) are encased and tethered, resulting in engorgement of vessels and thickening of the jejunal wall. (Courtesy Dr. Ha, Asan Medical Center, Seoul, Korea.)

Abnormal Density of Mesenteric Fat The most frequent radiologic manifestation of mesenteric abnormalities is alteration of fat density or intensity. The mesenteric fat becomes hazy due to lymphedema (see Fig. 47-24), edema (Fig. 47-16), hemorrhage (Fig. 47-17), cellular iniltration by inlammation or neoplasm (Figs. 47-18 to 47-20; see Fig. 47-15), or ibrosis (see Fig. 47-14). It is described as “misty mesentery.”93 Focal misty mesentery can be due to local etiologies such as trauma, strangulated bowel obstruction, infectious and inlammatory bowel disease (IBD), pancreatitis (see Fig. 47-16), and ischemic mesenteric disease36,61 (Fig. 47-21). It is diffuse when it is due to systemic causes like portal hypertension (Fig. 47-22), hypoalbuminemia, or heart failure. Whether localized or diffuse, it is usually ill-deined but is sometimes well demarcated, as in segmental misty mesentery120 (Figs. 47-23 to 47-25; see Fig. 47-16) and mesenteric panniculitis.52 It is sometimes demarcated by a so-called tumoral pseudocapsule (see Figs. 47-16 and 47-23), which is a peripheral band of soft tissue attenuation. Depending upon the severity and cause of disease, the misty mesentery may show variable densities. From cases of lymphedema to edema, to inlammatory and neoplastic cell iniltration, to hemorrhage, and to ibrosis with calciications, the density of misty mesentery becomes higher. In cases of sclerosing mesenteritis (see Fig. 47-14)

Normal mesenteric lymph nodes are routinely seen at CT and MRI. They are more dramatically visualized and better appreciated on coronal images and following contrast enhancement (see Fig. 47-7). It is dificult to deine the criteria of a normal mesenteric lymph node. As in other areas of the body, the size, shape, number, and distribution of nodes should be considered. Abnormality is generally deined as any mesenteric lymph node that measures larger than 6 mm in short axis or when a group of three or more lymph nodes is clustered in one anatomic location.19,81,82,83 A variety of diseases or conditions lead to mesenteric lymphadenopathy. Notably, lymphoma is the most common neoplastic cause (Figs. 47-31 and 47-32). Non-Hodgkin’s lymphoma in particular involves mesenteric nodes, usually along with paraaortic nodes. Hodgkin’s lymphoma usually does not involve mesenteric nodes. GI tract malignancy frequently metastasizes to regional mesenteric lymph nodes. Genitourinary tract malignancy and extraabdominal malignancy seldom metastasize to mesenteric nodes. Inlammatory or infectious GI tract disease frequently cause regional mesenteric lymphadenopathy, but their size is usually less than 10 mm83 (Fig. 47-33). In the case of primary mesenteric lymphadenitis, inlamed lymphadenopathy is the sole inding, without accompanying abnormal bowel changes, although an underlying infectious terminal ileitis is thought to be the cause83 (Fig. 47-34). Other systemic diseases like systemic lupus erythematosus, systemic mastocytosis, and sarcoidosis may show mesenteric lymphadenopathy. Hypodense lymphadenopathy with Whipple’s disease has been overly emphasized; it is not a unique inding for Whipple’s disease. Hypodense lymphadenopathy is more commonly seen in other benign and malignant diseases, notably in abdominal tuberculous or atypical tuberculous disease (Figs. 47-35 and 47-36) and Kaposi’s sarcoma. Furthermore, Whipple’s disease is extremely rare.35 It is also worthwhile to recognize mesenteric cavitary lymph node syndrome as an entity characterized by cystic change in mesenteric lymph nodes and associated with celiac sprue.54 Text continued on p. 1503

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FIG 47-16 Mimics of mesenteric panniculitis. A and B, Axial postcontrast CT images show hazy iniltration of the small bowel mesentery (white arrows) due to appendicitis (white arrow in B). C, A band of soft tissue—the tumoral pseudocapsule (black arrows)—demarcating a “misty mesentery” in a patient with Crohn’s disease. D, A hazy central small bowel mesentery (white arrows) with prominent lymph nodes (black arrows) in a patient who had been treated for testicular cancer. E, Misty mesentery (white arrow) with mesenteric vein engorgement (black arrow) in a patient previously treated for lymphoma. F, Hazy mesentery in a patient with pancreatitis. Fat ring sign (C to F) is well seen around vessels and lymph nodes.

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D FIG 47-17 Seatbelt injury. A and B, Axial CT images demonstrate a bowel wall and mesocolic hematoma in the cecum (white arrows) in a patient following blunt abdominal trauma sustained from a motor vehicle accident. The patient was wearing a seatbelt at the time of impact. B, urinary bladder. C and D, Images more superiorly show bruising in the abdominal wall in the right lower and left upper quadrants (white arrows) in the distribution of the seatbelt.

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B FIG 47-18 Sigmoid diverticulitis in two patients. A, Coronal reformatted CT shows abundant inlammatory changes (black arrow) surrounding the sigmoid colon, which has multiple diverticula (arrowheads) and a small luid collection within the sigmoid mesentery (white arrow). B, Axial CT in another patient with sigmoid diverticulitis demonstrating soft tissue stranding in the mesenteric fat adjacent to diverticula (black arrows). There is a large associated abscess (A). Urinary bladder is displaced anteriorly (U).

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F FIG 47-19 Active inlammatory bowel disease in two different patients. A to D, Serial axial CT images from a patient with Crohn’s disease show a focal segment of thickened distal and terminal ileum (white arrows). Prominence of the vasa recta (black arrowheads in B) indicates active inlammation. Soft tissue inlammatory changes are also evident in the RLQ mesentery (curved black arrow in A). There is abundant fatty proliferation of the mesenteric fat in the small bowel and sigmoid colon (F). E and F, CT images from another patient with active Crohn’s colitis show inlammatory changes in the ibrofatty proliferation of the sigmoid mesocolon (white arrows). Wall thickening and phlegmonous changes of the sigmoid colon are also present (arrowhead in F).

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FIG 47-20 Small bowel carcinoid metastatic to mesentery and liver. A and B, Contrast-enhanced CT of the lower abdomen demonstrates a spiculated soft tissue mass in the mesentery (white arrows) with a “spoke-wheel” arrangement of the mesenteric vessels (black arrows). Adjacent small bowel thickening (curved arrows) represents bowel ischemia. C, CT image through the liver shows the typical enhancing metastatic lesions to the liver.

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FIG 47-21 Thrombosis of branches of the SMV in two different A

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patients. A and B, Axial CT images in the lower abdomen, showing more distal thrombus (white arrows) in branches of the SMV, with resultant mesenteric haziness, relecting edema (black arrow in B). C, A different patient with thrombus in small tributaries of the SMV (black arrows), marked bowel wall edema (white arrows), and ascites (A).

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B FIG 47-22 Liver cirrhosis with mesenteric edema and omental collateral. A, Nonenhanced CT at the mid abdomen shows omental collaterals (white arrows) mimicking mild omental caking. B, Lower-level CT slice shows hazy ill-deined mesenteric edema (black arrow). Note that engorged mesenteric vessels appear radiating. Small bowel wall is also thickened (arrowhead).

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D FIG 47-23 Mesenteric panniculitis in a 70-year-old man. A to D, Serial axial CT images show segmental increased attenuation in the small bowel mesentery, separated from the adjacent fat by a tumoral pseudocapsule (black arrows in B). There is preservation of the fat around vessels (fat ring sign) that are surrounded by the increased density (white arrows in C) (Courtesy Dr. Ha, Asan Medical Center, Seoul, Korea.)

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D FIG 47-24 Idiopathic “misty mesentery.” A and B, Serial contrast-enhanced axial CT images show mild increased attenuation in the small bowel mesenteric fat (white asterisk). Additional linear branching soft tissue structures are within the mesentery, which are not identiiable as veins or arteries. These soft tissue structures are better appreciated on a coronal reformatted CT image (C) and presumably represent dilated lymphatics. D, A more anterior coronal reformatted CT image, redemonstrates the “misty mesentery” (arrow).

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B FIG 47-25 Idiopathic “misty mesentery” in a patient with chronic abdominal pain. A, Axial enhanced CT image shows increased attenuation in the small bowel mesentery, with a tumoral pseudocapsule (arrows). B, Findings were relatively stable after 2 years.

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C FIG 47-26 Omental GIST. Axial CT (A and B) and coronal reformatted CT (C) show a heterogeneously enhancing mass in the greater omentum (arrows). This mass extends to the pelvic cavity (arrowheads). D, Cut section of specimen shows large mass with hemorrhagic necrosis.

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B FIG 47-27 Mesenteric ibromatosis. A and B, Axial CT at two different levels of the abdomen show a soft tissue mass in the mesentery encasing mesenteric vessels (arrows) in a patient with total colectomy for Gardner’s syndrome.

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E FIG 47-28 Solitary ibrous tumor arising in the mesentery. Axial CT (A and B) and coronal reformatted CT (C and D) show a well-deined hypervascular mass in the mesentery (arrows). E, Cut section of specimen shows well-deined yellow to white mass with hemorrhagic necrosis.

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FIG 47-29 Cystic lymphangioma in transverse mesocolon. A to D, Axial CT at multiple levels through the abdomen and pelvis show a low-density mass lesion in the transverse mesocolon (arrows). Transverse colon appears to be loating in the mass. Minimal mass effect on adjacent small bowel loops is seen (arrowhead).

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D FIG 47-30 Cystic lymphangioma in mesentery. A to C, Axial CT at multiple levels show low-density mass lesion in the mesentery (arrows). Minimal mass effect on adjacent small bowel loops is seen (arrowhead). D, Surgical specimen shows well-deined yellow mass in the mesentery.

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FIG 47-31 Lymphoma. A to D, Four consecutive axial CTs of the abdomen and pelvis show conglomerate mesenteric lymph nodes (arrows). Mesenteric vessels (arrowheads) are surrounded and engulfed by the mass but not encased, distorted, or narrowed. Note a bulky mass in cecum (black arrows).

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D FIG 47-32 Lymphoma. Axial CT (A and B) and coronal reformatted CT (C and D) images of the abdomen and pelvis show omental caking (arrowheads) and a bulky masslike lymphoma implantation onto pleats of right side omentum (arrows).

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mimic omental cake due to peritoneal carcinomatosis or peritonitis (Fig. 47-43; see Fig. 47-22). Mesenteric venous congestion or dilatation of veins is seen in high-grade bowel obstruction, segmental misty mesentery,120 or active IBD. Mesenteric venous air is an important sign of necrotizing enteritis.

PRIMARY MESENTERIC DISEASES Congenital

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B FIG 47-33 Ileocolic lymphadenopathy with appendicitis. A, Lower abdominal CT during acute appendicitis shows several enlarged lymph nodes (arrows). B, Following antibiotic treatment these lymph nodes (arrows) dramatically decrease in size.

One commonly encounters cases of unexplainable mesenteric lymphadenopathy, most of them clinically insigniicant and irrelevant. The best strategy to deal with concern is short-term follow-up study. If no changes arise in the short term, long-term follow-up can be done. If the lymphadenopathy still does not change, one can ignore it.

Abnormal Mesenteric Vessels Mesenteric disease may result from changes of the mesenteric vessels. Arterial thrombosis or embolism or venous thrombosis cause ischemic mesenteric (bowel) disease (Figs. 47-37 to 47-39; see Fig. 47-21). Mesenteric venous or arterial collaterals suggest current or past occlusion of mesenteric vessels or portal hypertension.50 Alteration of mesenteric vessels in position, course, and shape can be important clues of certain bowel-related diseases. When whirling of mesenteric vessels is associated with bowel obstruction, volvulus is the most likely cause.78 In congenital nonrotation or malrotation of bowel, the relationship of the SMA and superior mesenteric vein (SMV) is reversed (Fig. 47-40). Anterior displacement of the inferior mesenteric vein (IMV) by clustered small bowel loops is the sign of left paraduodenal hernia (Fig. 47-41), whereas anterior displacement of the right colic vein by clustered small bowel loops is the sign of right paraduodenal hernia131 (Fig. 47-42). When there is portal hypertension, multiple mesenteric varices develop. Omental varices sometimes

Congenital defects within the mesentery cause internal hernias. Depending upon the different locations of the defect, different types of internal hernia occur. The most common internal hernias are right and left paraduodenal hernias, where the mesenteric defect occurs around the duodenojejunal junction (see Figs. 47-41 and 47-42). Much less commonly a defect in the small bowel mesentery or mesocolon can cause a transmesenteric hernia. When herniated bowel loops are incarcerated with or without volvulus, indings are those of closedloop obstruction. The mesenteric defect itself is not visualized, and it is dificult to distinguish from other causes of closed-loop obstruction. However, unique displacement of certain mesenteric vessels by clustered bowel is highly suggestive of certain forms of paraduodenal hernia131 (see Figs. 47-41 and 47-42). Malrotation is a congenital abnormal position of the bowel within the peritoneal cavity; it is due to faulty rotational or ixational evolution of the gut, usually involving both the small and large bowel. Abnormal bowel ixation by mesenteric bands (Ladd’s bands) or absence of ixation of portions of the bowel lead to increased risks of bowel obstruction with or without volvulus. Many subtypes of malrotations exist and involve various degrees of malrotation; the position of the duodenojejunal junction and colon depends on the developmental stage at which normal embryologic rotation failed. Some patients with malrotation show signs of bowel obstruction soon after birth (e.g., bilious vomiting), but some people affected by malrotation may not be diagnosed until long after infancy, and often it may be an incidental inding. In patients with malrotation the mesenteric attachment of the midgut, particularly the portion from the duodenojejunal junction to the cecum, is abnormally short. The bowel has an increased propensity to twist counterclockwise around the SMA and SMV, which is known as midgut volvulus. Midgut volvulus may present as intermittent abdominal pain and may cause bowel necrosis.2 Diagnosis is usually made on an upper GI series, which remains the imaging standard and shows an abnormal duodenojejunal junction, usually in the right abdomen or at least to the right of midline. On a CT the duodenum does not cross the midline, and no clear duodenojejunal junction is identiied. Most small bowel loops are in the right side of the abdomen, and colonic loops are in the left. Additionally, mesenteric bands may lead to external obstruction, especially in the duodenum or ileum. Twisting can result in a whirl-like pattern on CT. The relationship between the SMA and SMV may also be reversed, with the SMV to the left of the SMA33 (see Fig. 47-40).

Neoplasm Primary neoplasm—either cystic or solid—of the mesentery is very rare; however, mesenteric ibromatosis is worth mentioning.108 Also known as intraabdominal ibromatosis or abdominal desmoid tumor, mesenteric ibromatosis is a locally aggressive but benign proliferative tumor that does not metastasize. It is part of the spectrum of deep ibromatoses, and the small bowel mesentery is the most common site of intraabdominal ibromatosis.76,124 Most cases are sporadic, but approximately 10% to 15% occur in patients with familial adenomatous polyposis (FAP) (i.e., Gardner’s

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D FIG 47-34 Mesenteric adenitis. A to D, Axial CT of the lower abdomen and pelvis shows multiple enlarged RLQ mesenteric lymph nodes (white arrows in A and B) and mild thickening of the terminal ileum (white arrows in C and D) in a pediatric patient presenting with RLQ pain. The appendix is normal (black arrows in C and D).

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FIG 47-35 Mesenteric adenopathy in a 41-year-old man with HIV, AIDS, and Mycobacterium avium complex (MAC). A to D, Serial axial contrast-enhanced CTs show conglomerate adenopathy (white arrows) in the mesentery. More discrete enlarged nodes are in the RLQ (black arrow). Nodes are of homogenous soft tissue attenuation. Note vascular engorgement and perivascular edema (black arrowheads).

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D FIG 47-36 Tuberculous lymphadenopathy. A to D, Axial CT of the abdomen and pelvis shows multiple enlarged lymph nodes in the mesentery (arrows). A hypodense center is noted (arrowhead).

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FIG 47-37 SMA embolus. A, Curved planar reformatted image of the SMA shows a illing defect (arrow) in a branch of the SMA consistent with an embolus in a patient with known atrial ibrillation. B, Another curved planar reformatted image shows abnormal enhancement and wall thickening in a long segment of ileum (arrows) related to ischemia.

syndrome variant). About 83% of mesenteric ibromatosis with FAP patients have a history of abdominal surgery, most commonly total colectomy. Only about 10% of sporadic mesentery ibromatosis cases have had previous abdominal surgery. Patients with FAP may have ibromatosis in and around anastomotic or surgical incision sites. Abdominal desmoids can be solitary or multiple, and their CT manifestations are variable. CT indings include a focal mesenteric mass (see Fig. 47-27) that may either have a highly collagenous stroma demonstrating soft tissue density or a myxoid stroma that appears more hypodense. Lesions can have mixed collagenous and myxoid stroma and may appear striated or whorled because of their alternating composition. Iniltration into adjacent organs or growth into the abdominal wall musculature of the psoas muscle is occasionally noted. Variable contrast enhancement is seen because myxoid components do not enhance. CT is useful for planning surgical resection and predicting the patient’s prognosis. Large size, multiplicity, extensive iniltration, tethering, and encasement of small-bowel loops are poor prognostic CT indings. On MRI, there is low to intermediate T1 signal and intermediate T2 signal, with variable contrast enhancement after gadolinium injection.5 Interestingly, some lesions that do not enhance on CT may enhance on MRI with gadolinium. Treatment of mesenteric ibromatosis is controversial. Although surgery is an option, these lesions can recur and surgery predisposes these patients to complications of bowel obstruction and istulas. Surgery involving cases of sporadic mesenteric ibromatosis are frequently curative. FAP mesenteric ibromatosis carries signiicantly higher rates of recurrence and disease is more dificult to control, so

surgery is often reserved to treat complications; nonsurgical methods are used initially.73 Extrapleural solitary ibrous tumor is a tumor of submesothelial origin with histology identical to that of solitary ibrous tumor of the pleura. Locations other than the pleura and mesentery include the lung, mediastinum, pericardium, peritoneum, extraperitoneal spaces, nose, and paranasal sinuses. The few case reports in the literature describe a well-deined mass with solid and cystic features on crosssectional modalities. The natural history is unknown, but because solitary ibrous tumor of the pleura may be aggressive, long-term follow-up is necessary.73 Cystic lymphangioma of the mesentery is a rare lesion but the most common cystic lesion involving mesentery. It can occur as a solitary cystic lesion or a more diffuse form (see Fig. 47-29). This tumor can occur in retroperitoneal locations alone or along with mesentery. Although benign in nature, it can cause symptoms if it attains large size and occurs in critical locations. This tumor should be differentiated from other types of cystic lesions of mesentery and omentum. These include enteric cyst, enteric duplication, mesothelial cyst, peritoneal inclusion cyst, and nonpancreatic pseudocyst.128 It is dificult to diagnose the different types of cystic lesions by imaging studies alone, particularly solitary forms.142 CT and MRI can provide important preoperative information regarding anatomic location, organ involvement, cyst size, and complications. A typical feature seen on a CT image is that multilocular masses often contain complex luid. The presence of streaky low densities within a multicystic lesion is very suggestive of a cystic lymphangioma. MRI best displays the solid cystic

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C FIG 47-38 SMA thrombosis and ileal ischemia. Axial CT (A and B) and coronal reformatted CT (C) images of the abdomen and pelvis show a illing defect (arrowhead) in SMA consistent with a thrombosis. Small bowel loops show poor enhancement and air in the wall (arrows). Surgical specimen shows transmural ischemic necrosis in the involved small bowel.

CHAPTER 47 components, which aids in the preoperative diagnosis and surgical planning. Benign or malignant mesenchymal tumors of fat cell, muscle cell, nerve sheath cell, or connective tissue cell origin can develop in the mesentery very rarely (Fig. 47-44). GI stromal tumors can occur rarely as primary tumors of the mesentery, but it is often debatable whether they originated from the bowel wall or mesentery27,64,72,119,121 (see Fig. 47-26). Other common neoplasms originating from other sites that involve the mesentery include lymphoma, Kaposi’s sarcoma, and metastatic disease (e.g., carcinoid tumor; see later).71

Infectious and Inlammatory Disease Primary infectious and inlammatory diseases of the mesentery are rare. Most infectious and inlammatory diseases of the mesentery are

FIG 47-39 SMV thrombosis. Coronal reformatted image shows extensive occlusive thrombus (arrows) in the jejunal and ileal tributaries of the SMV in a patient who is hypercoagulable.

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secondary to infectious or inlammatory bowel disease or peritonitis and will be discussed further under “Secondary Mesenteric Diseases.” However, sclerosing mesenteritis, mesenteric lymphadenitis, and less importantly inlammatory pseudotumor are unique disease entities that occur as primary forms and deserve further mention.

Sclerosing Mesenteritis. Sclerosing mesenteritis is a rare benign disorder characterized by nonspeciic inlammation of mesenteric fat. It is distinguished histologically by varying amounts of ibrosis, chronic inlammation, and fat necrosis.30 This protean process has been known by a number of terms such as mesenteric panniculitis, mesenteric lipodystrophy, and retractile mesenteritis. Confusion surrounds these terms because they are often used synonymously in the literature and may describe histologic features or subtypes of different stages of the same disease. However, radiologically on CT there are two distinct forms: sclerosing mesenteritis and mesenteric panniculitis. Sclerosing mesenteritis usually involves the small bowel mesentery at its root but can sometimes affect the mesocolon and rarely the peripancreatic region, omentum, retroperitoneum, or pelvis.38,52 Its etiology remains unknown, although various causes have been suggested, including infection, ischemia, trauma, and vasculitis. There is a suggestion that it may link with immunoglobulin (Ig)G4-related sclerosing disease, because it has been associated with retroperitoneal ibrosis, Riedel’s thyroiditis, orbital pseudotumor, and sclerosing cholangitis. An association between prior abdominal surgery and sclerosing mesenteritis has been also reported. The average age of patients at presentation is 60 years, and the condition is more common in males than females. Patients may present with an abdominal mass, pain, bowel obstruction, bowel ischemia, or diarrhea. Not uncommonly, sclerosing mesenteritis may be an incidental inding in an asymptomatic patient. The CT appearance of sclerosing mesenteritis relects the underlying histology of the lesion (see Fig. 47-14). Most commonly it presents as a soft tissue mass with variable enhancement (Fig. 47-45). The mass may show well-circumscribed or iniltrating margins, and lesions may contain central calciication, possibly related to fat necrosis (Fig. 47-46). Larger masses may demonstrate cystic features, suggesting necrosis. Enlarged mesenteric or retroperitoneal nodes may be associated. Linear bands of ibrosis may radiate from the mass, affecting the small bowel by retraction and shortening of the mesentery rather than by direct invasion. The small bowel may then become kinked or ixed,

B FIG 47-40 Malrotation of the intestine. A and B, Two consecutive axial CTs show reversal of the SMA (arrow) and SMV (arrowhead) position, with SMV being to the left of the SMA.

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B FIG 47-41 Left paraduodenal hernia. Axial (A) and coronal (B) CTs show contained clustered loops of small bowel in left upper abdomen. Note the anterior displacement of inferior mesenteric vein (arrow). (Courtesy Dr. Choi, Seoul National University Hospital, Seoul, Korea.)

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D FIG 47-42 Right paraduodenal hernia in an asymptomatic patient. A to D, Serial contrast-enhanced axial CTs demonstrate mildly dilated small bowel loops herniating into Waldeyer’s fossa (curved arrow). The right colic vein (straight white arrows) is displaced anteriorly by the herniated bowel loops.

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B FIG 47-43 Mesenteric and omental collateral vessels. A, Axial contrast-enhanced CT image shows a tangle of tortuous (long arrow) collateral vessels in the region of the pancreatic head in a patient with cavernous transformation of the portal vein from cryptogenic cirrhosis. Multiple small collaterals are also within the omentum (short arrow). B, More inferiorly numerous mesenteric collaterals are evident (long arrow), and small collaterals are also seen in the omental fat within an incisional hernia (short arrow).

resulting in obstruction; obstruction of lymphatics and veins may cause edematous thickening.52,67,73 On MRI, sclerosing mesenteritis has been reported to have signal intensity patterns consistent with ibrosis—low to intermediate signal intensity on T1- and low signal intensity on T2-weighted images.7,66 Sclerosing mesenteritis has also been reported to have high signal intensity on T2-weighted images,60,65 likely corresponding to the disease phase dominated by myxomatous change or active proliferation of ibrosis accompanied by hypervascularity.73 Lymphoma and small bowel carcinoid are the main differential diagnostic considerations for a soft tissue mass within the mesentery. Lymphoma, however, does not usually calcify unless previously treated and does not often cause bowel ischemia. Lymphoma is also more likely to demonstrate discrete enlarged nodes. Serotonin production from small bowel carcinoids can produce a ibrotic retraction that may cause desmoplastic kinking of the small bowel similar to the retraction observed at CT in cases of sclerosing mesenteritis. However, focal small bowel mural thickening or mass favors the diagnosis of carcinoid. Additionally, most small bowel carcinoid tumors are positive on somatostatin-receptor scintigraphy, and imaging with indium-111 pentetreotide can differentiate between the two diseases. Benign entities in the differential include atypical infectious etiologies such as Whipple’s disease, which may affect the mesentery and retroperitoneum with lipogranulomatous inlammation. A diagnosis of Whipple’s disease can be made by using a polymerase chain reaction to verify the causative bacillus. Actinomycosis can also cause an aggressive iniltrative soft tissue process at CT and may affect the mesentery (see Fig. 47-48). Additionally, Weber-Christian disease, a rare systemic inlammatory disorder of fat, may have multifocal areas of fat necrosis and inlammation in the mesentery that may be identical to sclerosing mesenteritis. Differentiation of Weber-Christian disease from sclerosing mesenteritis relies on identiication of other features of the disease. Typically these patients also have lower extremity skin nodules, fevers, myalgias, arthritis, and arthralgia. Other benign ibrous lesions such as mesenteric ibromatosis, inlammatory pseudotumor, and extrapleural solitary ibrous tumor may also be considered within the differential. Deinitive diagnosis of sclerosing mesenteritis requires histology, and surgical excisional biopsy is often needed for complete analysis.

Depending on the severity of symptoms, treatment may consist of simple observation, medical therapy with steroids, colchicine, orally administered progesterone, or immunosuppressive agents. Surgical resection may be indicated for those patients with complications such as bowel obstruction or perforation. Mesenteric panniculitis appears as subtle increased attenuation within the mesenteric fat, often at the root of the mesentery, with accompanying small nodes (Fig. 47-47; see Fig. 47-23). It may also exhibit a tumoral pseudocapsule consisting of a peripheral band of soft tissue attenuation that separates the normal mesentery from the inlammatory process118 and may show spared fat around vessels and lymph nodes—the fat ring sign.134 It does not progress or change for long periods and is mostly found incidentally on CT. It is self-limited and does not cause signiicant clinical issues. Although mesenteric panniculitis and sclerosing mesenteritis appear quite different on CT, it can be more dificult to distinguish them pathologically because both have inlammation, fat necrosis, and ibrosis. If ibrosis is the dominant feature, the diagnosis is sclerosing mesenteritis; if inlammation and fat necrosis are dominant features, the diagnosis is mesenteric panniculitis. These do not appear to be different stages of one disease spectrum, because no case of mesenteric panniculitis progressing to sclerosing mesenteritis has been reported. When one makes a diagnosis of mesenteric panniculitis, the rare possibility of mesenteric lymphoma, which has overlapping CT features with mesenteric panniculitis, should be excluded. Therefore it is essential to document stability of the lesion over a reasonable period of time to reach the diagnosis of mesenteric panniculitis by follow-up study or comparison with old studies if available. It is not known what causes mesenteric panniculitis or sclerosing mesenteritis. There are cases where CT indings of mesenteric panniculitis and possible causes are conjoined: chronic pancreatitis, IBD, stigmas of prior abdominal surgery, and prior trauma. Misty mesentery is another confusing term. This is not a disease entity but rather CT descriptive terminology. Regardless of the etiology of the condition (e.g., edema, lymphedema, cellular iniltration by inlammation or neoplasm, ibrosis, bleeding in the mesentery), mesentery shows hazy increased density on CT24,93,120 (Fig. 47-48; see Figs. 47-16, 47-24, and 47-25). Most of these conditions are transient and

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E FIG 47-44 Omental schwannoma. A, Sagittal T2-weighted MRI shows heterogeneously bright round mass (arrow) in the greater omentum. Postgadolinium early enhanced T1-weighted axial MRI (B) shows peripheral enhancing mass (arrow), and delayed enhanced coronal MRI (C) shows further illing in of peripheral enhancement, but central part does not get enhanced, representing necrosis. D, Axial postcontrast CT shows similar enhancement pattern (arrow). Note mobility of the mass from MRI to CT. A large ibroid in the uterine fundus (arrowheads) was incidentally noted on sagittal MRIs. E, Surgical specimen shows a well-deined yellow mass in the mesentery. (Courtesy Dr. Choi, Seoul National University Hospital, Seoul, Korea.)

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FIG 47-45 Sclerosing mesenteritis. A to C, Axial CT images show a well-deined soft tissue mass (arrows) in the small bowel mesentery. There is mild mesenteric vessel engorgement (arrowhead). D, Surgical specimen shows yellow mass in the mesentery with speculated border (arrows).

temporary, and often the cause of the condition is readily apparent120 (see Figs. 47-16 and 47-17). Mesenteric panniculitis and sclerosing mesenteritis can be described as “misty mesentery” on CT initially, but chronicity of the condition and other unique indings will separate these two entities from other causes.

Inlammatory Pseudotumor. Inlammatory pseudotumor (inlammatory myoibroblastic tumor, extrapulmonary inlammatory pseudotumor, plasma cell granuloma, plasma cell pseudotumor, inlammatory ibrosarcoma) is a chronic inlammatory disorder of uncertain etiology.109 Although it most frequently occurs in lung and orbit, it can occur in many places including the mesentery (Fig. 47-49; see Fig. 47-15). Inlammatory pseudotumor may be due to the sequela of occult infection, minor trauma, or prior surgery and can be dificult to differentiate from malignant neoplasm or sclerosing mesenteritis. It most commonly occurs in the pediatric or young adult population. Symptoms include fever, malaise, weight loss, and abdominal pain. Surgical resection is usually curative.39,106

Mesenteric Adenitis. Mesenteric adenitis has been characterized as benign inlammation of mesentery lymph nodes, usually in the right lower quadrant (RLQ). It has been subdivided into primary and secondary forms. Primary mesenteric adenitis has been deined as rightsided mesenteric adenopathy without identiiable concomitant acute inlammatory process, and with or without wall thickening of the terminal ileum. Although designated as primary, these cases are thought to be due to an infectious process (e.g., Yersinia enterocolitica and Yersinia pseudotuberculosis) causing a terminal ileitis that may not be apparent on imaging. Secondary mesenteric adenitis has been

described as mesenteric adenopathy (usually right-sided) associated with an identiiable intraabdominal inlammatory process such as Crohn’s disease, infectious colitis, ulcerative colitis, or diverticulitis. Although appendicitis can also cause enlarged right-sided mesenteric lymph nodes, mesenteric adenitis is often considered important in the differential diagnosis of appendicitis, especially in children. Therefore appendicitis is not usually classiied as a form of secondary mesenteric adenitis even though enlarged right-sided lymph nodes are commonly identiied with this process. Commonly the signs and symptoms of appendicitis and mesenteric adenitis overlap, including RLQ pain, nausea, and vomiting. Rao et al.111 found in a retrospective study that 50 of 651 (7.7%) patients who had an admission diagnosis of appendicitis had a discharge diagnosis of mesenteric adenitis, and that prospectively 18 of 100 (18%) patients had mesenteric adenitis with signs and symptoms of appendicitis. Distinguishing these two entities is important because mesenteric adenitis is treated conservatively, whereas appendicitis is a surgical disease. A CT scan may be the best way of distinguishing these entities. A normal appendix would effectively exclude appendicitis. Detection of a cluster of three or more enlarged RLQ lymph nodes (>5 mm) in the presence of a normal appendix and no other acute inlammatory process except mild (5 mm) with a concomitant intraabdominal inlammatory process (other than appendicitis) would represent secondary mesenteric adenitis. Confusion exists in the literature over what to do with lymph nodes incidentally found in the mesentery. Macari et al.83 in 2002 did not ind

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D FIG 47-46 Sclerosing mesenteritis with dense calciication. A, Plain ilm of the abdomen shows calciication (arrows) in the left side of the abdomen. B to D, Axial CT images show an ill-deined soft tissue mass (black arrows in B) in the small bowel mesentery, with dense calciication (arrowheads in C). There is dilated and thickened small bowel (white arrows in D).

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FIG 47-47 A to C, Mesenteric panniculitis. Axial CT shows seg-

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mental increased attenuation in the small bowel mesentery, separated from the adjacent fat by a tumoral pseudocapsule (arrows in C). There are several enlarged lymph nodes in the mesentery (arrowhead in A).

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D FIG 47-48 A to D, Actinomycosis. Axial CT shows heterogeneously and irregularly enhanced mass in the mesentery, omentum, and abdominal wall (arrows in C and D). Hazy omentum is noted (arrowheads in A).

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D FIG 47-49 Inlammatory pseudotumor. Axial (A and B) and coronal reformatted (C and D) CTs of the abdomen and pelvis show spiculated soft tissue mass (arrows) in the omentum. Hazy omentum (arrowhead) is noted.

RLQ mesenteric nodes in a group of 60 patients who had CT scans for abdominal trauma, and inferred that otherwise healthy patients did not have abnormal RLQ lymph nodes. The cutoff used for abnormal lymph node size was 5 mm or greater in short axis. Lucey et al.81 in 2004 found that 47 of 120 (39%) patients had mesenteric lymph nodes larger than 3 mm in short axis (mean size, 3.6 mm [range 3-6 mm]; mean size of largest lymph node, 4.6 mm [range 3-9 mm]), who had otherwise negative CT scans for blunt abdominal trauma. Five of these 47 patients had these lymph nodes in the RLQ. The discrepancies may partially be explained by the size criteria used (5 mm vs. 3 mm) and possibly be due to improving multidetector computed tomography (MDCT) and picture archiving and communication system (PACS) technologies that may facilitate detection of smaller lymph nodes. Given these indings, we think it would be wise to diagnose primary mesenteric adenitis only in the presence of clinical symptoms such as abdominal pain. It is likely that as imaging technology improves, more and more incidental mesenteric lymph nodes will be detected and may not be of clinical signiicance.

Trauma Injury to the mesentery from blunt abdominal trauma is relatively uncommon, with variable incidences of 1% to 13% reported in patients undergoing emergent laparotomy.85,99,139 Despite its infrequency, mesenteric injury from blunt abdominal trauma is a signiicant source of morbidity and mortality, often the result of a delay in diagnosis. CT has been shown to be accurate in detecting mesenteric injury and is the diagnostic test of choice in hemodynamically stable patients who have suffered blunt trauma.85 In recent years CT has been found in both surgical and imaging studies to have reasonably high accuracy for detecting and characterizing mesenteric injuries. Numerous CT indings of mesenteric injury from blunt abdominal trauma have been well described in the literature.12-15,28,34,43,46,62,98,99,114,129 Penetrating injury to the mesentery, on the other hand, typically coexists with other severe injury and is typically diagnosed by surgical exploration rather than by imaging, owing to the patient’s hemodynamic instability, often from catastrophic intraabdominal hemorrhage (Fig. 47-50).

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B FIG 47-50 Mesenteric injuries and hematomas in a patient who had been in a motor vehicle collision. Axial precontrast (A), venous (B), and coronal reformatted (C) CTs of the abdomen and pelvis show a large hematoma on the left side (arrows). The high-attenuated contrast material (arrowhead) surrounded by a lowerattenuation hematoma is noted in the mesentery, suggesting mesenteric injuries with active bleeding.

Mesenteric injury may include contusion, laceration, and complete transection. Two mechanisms are thought to cause injury to the mesentery in blunt trauma: (1) crush or compressive force against the spinal column and (2) shear forces at the mesenteric attachments.53 The most commonly reported cause of mesenteric injury is a motor vehicle accident involving the use of seat belts—a situation where compressive and shear forces are both likely involved.53,117,139 The “seatbelt syndrome” is characterized by injuries in the plane of the seatbelt, often involving the mesenteries of the small bowel and colon. Patients may also have lumbar spine injuries (Chance fracture) and cutaneous bruising in the distribution of the seatbelt (“seatbelt sign”) (see Fig. 47-17). Additionally, injury to the small bowel mesentery is more frequent than injury to the colonic mesenteries,99 the most common locations involving the ligament of Treitz and the ileocecal region. These points of ixation of the mesentery are thought to be more susceptible to shearing forces.

Injuries to the mesentery result in an array of pathophysiologic processes. Laceration of the vessels may cause signiicant hemorrhage with subsequent hypovolemia and bowel ischemia. If the injury is unrecognized, bowel necrosis, peritonitis, and sepsis may ensue. Unrepaired small lacerations in the mesentery may allow for the formation of internal hernias and resultant bowel obstruction. Lastly, although rare, small tears or contusions of the mesentery may lead to partial-or full-thickness bowel ischemia with attendant mucosal ulceration, scarring, and bowel stenosis, eventually resulting in bowel obstruction. In the hemodynamically stable patient, MDCT plays a major role in the evaluation of mesenteric injury.28,64 CT indings that suggest mesenteric injury include active extravasation of intravenous (IV) contrast into the mesentery, mesenteric hematoma or iniltration associated with bowel wall thickening, isolated mesenteric hematoma or iniltration, and free intraperitoneal luid (Figs. 47-51 and 47-52). Other morphologic vascular changes on MDCT, such as vascular irregularity or abrupt termination of vessels, have also been described.15 Of

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D FIG 47-51 Mesenteric hemorrhage. A to D, Serial axial CTs demonstrate “misty mesentery,” increased attenuation in the small bowel mesentery (arrows) secondary to mesenteric bleeding in a patient following abdominal trauma from a motor vehicle accident.

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B FIG 47-52 Iatrogenic mesenteric trauma. A and B, Axial nonenhanced CT in a patient who developed mesenteric hematoma (H) following bowel resection, with resultant obstruction (arrows) of more proximal small bowel loops.

CHAPTER 47 these indings, active extravasation of IV contrast and bowel wall thickening associated with mesenteric hematoma/iniltration are the most speciic signs for determining the need for surgical intervention. Active extravasation of IV contrast into the mesentery has a speciicity of 100%15,28,62 for the diagnosis of signiicant injury and is usually an indication for urgent laparotomy. Despite its high speciicity, this inding is not common. Bowel wall thickening associated with mesenteric iniltration or hematoma is highly suggestive of signiicant bowel injury requiring surgery.28,62 Again, although speciic, these indings are not common. Mesenteric indings are more common when bowel injury is along the mesenteric border. The signiicance of an isolated mesenteric hematoma or isolated mesenteric iniltration is less clear with respect to surgical intervention. Although a hematoma is indicative of vascular laceration, this inding does not necessarily indicate a need for surgery. Furthermore, a number of studies have shown that patients with mesenteric iniltration or isolated hematoma who did not undergo surgery had resolution of indings on follow-up CT.95 Unexplained intraperitoneal free luid (i.e., in the absence of solid organ injury, urinary bladder rupture, previous peritoneal lavage) is not an uncommon inding in patients with mesenteric injury requiring surgery.13,28,62 The presence of this inding in blunt trauma patients raises the possibility of surgical mesenteric injury, but it may not mandate laparotomy. A large prospective multiinstitutional trial showed a low (8%) rate of surgical bowel injury in the setting of isolated free luid,77 and other retrospective trials have also noted that unexplained free luid is not predictive of surgical bowel or mesenteric injury.28,62,85 Rather, these patients may beneit from clinical monitoring and follow-up CT.

Vascular Disease Mesenteric ischemia is characterized by diminished blood low and an inadequate supply of oxygen to meet the metabolic demands of the bowel. Depending upon the severity of the insult, mesenteric ischemia may manifest variably from a transient change in bowel activity to frank bowel infarction and necrosis. Radiologic studies may detect the ischemic changes in the affected bowel loops and mesentery and determine the cause of ischemia. Common but nonspeciic indings detectable on both CT and MRI in mesenteric ischemia include bowel distention, bowel wall thickening, mesenteric edema, and ascites. More speciic indings may include lack of bowel wall enhancement and pneumatosis. In the past, catheter angiography was the gold standard for evaluating the mesenteric vasculature. However, with more recent developments in CT technology, MDCT angiography is probably the most frequently used technique for the diagnosis of mesenteric ischemia, with contrast-enhanced three-dimensional (3D) MR angiography (MRA) also being widely used.10,47,51,50,122,123 Mesenteric ischemia comprises a wide spectrum of disease processes that has traditionally been divided into acute and chronic causes given the stark contrast in clinical presentations.

Acute Mesenteric Ischemia. Acute mesenteric ischemia (AMI) is a potentially fatal vascular emergency with overall mortality of 60% to 80%.101,140 Clinical presentation is nonspeciic in most cases but has been classically characterized by sudden severe abdominal pain out of proportion to physical exam indings. AMI can be categorized into four speciic types by cause: arterial embolism, arterial thrombosis, nonocclusive causes, and venous thrombosis. Emboli to the SMA are the most frequent cause of AMI, responsible for approximately 50% of cases.47,101 Most emboli are cardiac in origin

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and may dislodge from a left atrioventricular thrombus (in the setting of atrial ibrillation or myocardial infarction) or valvular thrombus. More than 95% of patients with SMA occlusion have documented histories of cardiac disease, and nearly a third have a history of a preceding embolic event. The onset of symptoms is usually sudden as a result of the poorly developed collateral circulation. Acute severe abdominal pain may be associated with diarrhea that may become bloody. Most emboli wedge at branch points in the mid- to distal SMA distal to the middle colic artery, allowing the inferior pancreaticoduodenal branches to be perfused and the proximal jejunum to be spared101,140 (see Fig. 47-37). The angiographic hallmark of an embolic occlusion is abrupt termination of the vessel (cutoff sign). Nonocclusive emboli are usually seen as illing defects in the vessel lumen. Typically no collateral vessels are noted. Both CT angiography (CTA) and contrast-enhanced MRA can depict these indings. Arterial thrombosis accounts for approximately 25% of AMI and occurs in the setting of severe atherosclerotic disease (see Fig. 47-38). The slowly progressive nature of atherosclerosis usually allows for development of a collateral circulation so that ischemia occurs only after the inal artery supplying a bowel segment occludes. In up to 50% of cases, a history of intestinal angina is present. Additionally these patients tend to present with more extensive bowel ischemia/infarction than those with embolism. The perioperative mortality is high, ranging from 70% to 100% because of the delay in diagnosis, extent of bowel ischemia, and need for complex surgical revascularization. Unlike emboli, occlusion due to thrombosis usually involves the ostia and proximal 2 cm of the SMA. Typically no deined intraluminal illing defect or meniscus is noted on imaging, and a collateral circulation may be evident. Nonocclusive mesenteric ischemia accounts for 20% of AMI and typically occurs in patients with cardiac dysfunction. The pathophysiology of nonocclusive mesenteric ischemia appears to involve splanchnic vasoconstriction in response to hypovolemia, hypotension, decreased cardiac output, or drugs such as digoxin, diuretics, or β-blockers. The frequency of nonocclusive mesenteric ischemia among cardiac surgery and hemodialysis patients has increased over the last few decades, with 9% to 20% of deaths of hemodialysis patients attributable to nonocclusive mesenteric ischemia.140 Other risk factors for nonocclusive mesenteric ischemia include cardiac (infarction, congestive failure, aortic insuficiency), renal, or hepatic disease. Bowel changes are similar to those of occlusive mesenteric ischemia; however, the mesenteric vasculature remains patent. Watershed areas such as the splenic lexure of the colon are more vulnerable to nonocclusive mesenteric ischemia. CTA indings are similar to indings evident on conventional catheter angiography but are often subtle and dificult to diagnose. The mesenteric vessels are patent but may appear diffusely small in caliber with fewer side branches visible. Reduced opaciication of the bowel wall may also be evident. Acute mesenteric venous thrombosis is the least common cause, occurring in up to 10% of cases of small bowel ischemia. It is generally seen in younger patients, typically in the setting of abdominal surgery. Other predisposing factors include portal hypertension, abdominal or pelvic inlammation, trauma, renal or cardiac disease, oral contraceptive use, hematologic abnormalities, or a hypercoagulable state.10 The SMV is involved in 95% of cases (see Figs. 47-21 and 47-39). Involvement of the IMV and large bowel are uncommon. Mesenteric venous thrombosis often affects a focal segment of bowel with edema, hemorrhage, and mucosal sloughing. Occlusion of the proximal SMV rarely causes bowel necrosis, whereas occlusion of the distal SMV or its branches involving the vasa recta causes bowel necrosis by preventing development of collateral low. Both CTA and contrast-enhanced MRA have been shown to be highly accurate for the evaluation of thrombosis.44,137

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Chronic Mesenteric Ischemia. Patients with chronic mesenteric ischemia (CMI) typically have a more benign and indolent presentation than those with AMI, typically presenting with mesenteric angina—postprandial abdominal pain, fear of food, and weight loss. Also in contrast to AMI, the majority of cases of CMI are due to atherosclerotic stenosis or occlusion of the proximal portions of the mesenteric arteries. Although atherosclerosis of the mesenteric vessels is common, CMI is relatively uncommon owing to the extensive collateral circulation within the mesentery. It is generally thought that at least two of the three main vessels must be affected before symptoms present, and at least 85% of cases do involve both the SMA and celiac axis.96 Involvement of only one vessel may occur but is uncommon. Unlike in patients with AMI, the small intestine usually appears normal in patients with CMI unless an acute thrombus is also present. In patients with CMI, mesenteric collateral vessels may form to preserve adequate blood low to the intestines. These can also be identiied at MDCT with 3D reformatting. Nonatherosclerotic causes of CMI are uncommon but include vasculitis due to connective tissue disorders and postradiation vasculitis. Fibromuscular dysplasia, abdominal coarctation, neuroibromatosis, and idiopathic ibrosis are also rare causes. Findings associated with vasculitides include stenosis, occlusion, aneurysm formation, vascular wall thickening and enhancement. The radiologic indings in various types of vasculitides may signiicantly overlap. Nevertheless, vasculitides should be considered whenever mesenteric ischemic changes are observed in young patients, coexist at unusual sites such as the stomach, duodenum, and rectum, involve both the small and large intestine, and are associated with genitourinary involvement or splenomegaly. Radiation enteritis is an infrequent sequela of abdominopelvic radiation therapy but a signiicant cause of morbidity. Radiation vasculitis and associated enteritis may develop as soon as 6 to 24 months after treatment but can present up to 20 years after the initial insult.63 The underlying pathologic process is an endarteritis obliterans— compromise of the microvascular circulation.17 The involved bowel segments depend on the radiation ield, and this inding may point to the underlying cause. Diagnosis of chronic radiation enteritis is often problematic because of the latency period. CT indings are nonspeciic but include thickening of the bowel wall and adjacent mesentery, increased density of the mesenteric fat, and conluent or adherent bowel loops. Barium studies may also demonstrate thickened valvulae conniventes, wall thickening, effacement of the mucosal fold pattern, ulceration, stenosis, and adhesions. Sinuses and istulas may be demonstrated by either barium study or CT exams. Because of the variability and nonspeciicity of indings in mesenteric ischemia, particularly in cases of nonocclusive and chronic ischemia, careful clinical correlation with CT indings is essential in evaluating patients with suspected mesenteric ischemia.

Appendices Epiploicae and Ischemic Infarction of Omentum Epiploic appendagitis. Appendices epiploicae are pedunculated fatty structures that arise from the serosal surface of the colon; they may measure 0.5 to 5 cm long and extend from the cecum to the rectosigmoid junction. Because of their pedunculated shape and mobility, appendices epiploicae may torse, leading to ischemic or hemorrhagic infarction. The resulting focal inlammatory process is termed epiploic appendagitis. Clinically, acute epiploic appendagitis manifests with acute onset of pain, typically in the lower quadrants, and is often clinically mistaken for appendicitis or diverticulitis. However, patients with

FIG 47-53 Epiploic appendagitis. Axial contrast-enhanced CT shows an ovoid fatty lesion adjacent to the cecum, with a hyperattenuating rim and surrounding inlammatory changes (short arrow). There is a vague hyperattenuating central area representing a thrombosed vessel or hemorrhage (long arrow).

epiploic appendagitis are usually afebrile with a normal white blood cell count.107,126 Epiploic appendagitis most commonly occurs in the sigmoid colon, followed by the descending colon and right colon. Typical CT indings include a paracolonic ovoid fatty mass (representing the infarcted or inlamed appendix epiploica) with surrounding inlammatory change, a well-deined hyperattenuating rim around the mass (relecting the inlamed peritoneal lining), and on occasion, central high attenuation possibly representing thrombosed vessels or hemorrhage107,112,126 (Fig. 47-53). Mild local reactive thickening of the adjacent colonic wall may also be evident. Acute epiploic appendagitis is treated conservatively with oral antiinlammatory medication; antibiotics are not routinely indicated. The condition is self-limited and most patients recover with conservative management in less than 2 weeks. CT indings may persist longer but typically resolve by 6 months. Omental infarction. The greater omentum, composed of a double layer of peritoneum, hangs from the greater curvature of the stomach and the proximal part of the duodenum covering the small bowel. At CT it appears as a band of fatty tissue of variable thickness just beneath the anterior abdominal wall and anterior to the stomach, transverse colon, and small bowel. Multiple small omental vessels are usually visible. Similar to epiploic appendagitis, torsion of the omentum or venous thrombosis of the omental vessels may lead to omental infarction, which usually occurs in the right lower or right upper quadrant, clinically mimicking appendicitis or cholecystitis. This bias for the right side of the abdomen is theorized to be related to variant embryologic vascular development predisposing to right-sided venous thrombosis.31 Other contributing factors include obesity, strenuous activity, congestive heart failure, digitalis administration, recent abdominal surgery, and abdominal trauma.126 Most cases occur in adults, but approximately 15% of cases affect the pediatric population41 (Figs. 47-54 and 47-55). Trauma, including rapid rotary movements, sustained blows to the abdomen, sudden change in body position, coughing, and straining, have been implicated as possible factors that may initiate primary torsion of the omentum. Secondary torsion is more common and can be induced by torsion caused by adhesion of the omentum and pathologic foci such as surgical scars, inlammation, cysts, tumors, and hernias and by thrombosis due to various causes such as hypercoagulopathy and vascular abnormalities. Regardless of the cause, similar patterns of progression from edema and congestion

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D FIG 47-54 Omentum infarction. Axial (A to C) and coronal reformatted (D) CTs of the abdomen and pelvis show an oval-shaped streaky iniltration in the right side of the omentum (arrows). Coronal reformatted CT image clearly demonstrates streaky iniltration in the right side of omentum (arrows).

due to venous stasis and thrombosis to hemorrhagic necrosis and extravasation of serosanguineous peritoneal luid are histopathologically observed. CT indings of omental infarct may vary from hazy soft tissue iniltration to a large heterogeneous mass. Most commonly the inlammatory mass is in the RLQ anteromedial to the ascending colon or anterior to the transverse colon.110 Although omental infarction may be dificult to distinguish from epiploic appendagitis, the inlammatory mass associated with omental infarction is typically larger. Like epiploic appendagitis, however, the condition is self-limited and only conservative management is required.107,126

Mesenteric Collateral Circulation. Recognition of arterial collaterals in the mesentery is important in detecting occlusions and ste-

noses of the major mesenteric branches in the evaluation of suspected mesenteric ischemia. The marginal artery of Drummond is situated along the mesenteric border of the colon and formed by the anastomotic continuation between the right, middle, and left colic arteries. The marginal artery of Drummond serves as the connection between the distal branches of the SMA and inferior mesenteric artery (IMA). Riolan’s arch, the principal pathway between proximal branches of the SMA and IMA, is located more centrally within the mesentery and is an inconstant anastomosis between the middle and left colic arteries. The meandering artery is also within the mesentery and is a very large tortuous vessel communicating between the SMA and IMA. It potentially represents an enlarged Riolan’s arch. Barkow’s arch is another collateral pathway between the SMA and the gastroepiploic artery.

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FIG 47-55 Omental infarcts in two different patients. A and B, Two consecutive axial enhanced CTs in a 6-year-old girl with chronic abdominal pain for 2 months demonstrate irregular soft tissue in the omental fat (arrows) in the right upper quadrant anterior to the ascending colon. C and D, Images from a PET/CT study obtained for evaluation of a solitary pulmonary nodule in an adult patient with RLQ abdominal pain shortly following colectomy demonstrate a large area of soft tissue iniltration in the RLQ (C). The fused PET/CT image (D) demonstrates mild FDG uptake consistent with inlammation.

Collateral venous pathways in the mesentery typically develop from portal hypertension or occlusion of the portomesenteric vasculature secondary to inlammatory or neoplastic pancreatic disease. Mesenteric varices from portal hypertension are not common but have been described as dilated and tortuous branches of the SMV in the leaves of the mesentery23 (see Fig. 47-43). Mesenteric venous collateral pathways may arise from either the SMV or IMV and ultimately drain into the systemic circulation through pelvic or retroperitoneal networks. Occasionally there may be direct shunts from the mesenteric veins to the inferior vena cava or renal veins. GI bleeding from lower intestinal varices is reported to occur in up to 5% of patients with portal hypertension.1,23 Omental collaterals are also infrequently observed but when present can mimic the appearance of omental implants (see Figs. 47-22 and 47-43).

SECONDARY MESENTERIC DISEASES Bowel Origin Various infectious, inlammatory, and neoplastic processes originating in the bowel can involve the adjacent mesentery and show vascular engorgement, mesenteric haziness, and mesenteric lymphadenopathy.

Infection. Infections of the GI tract commonly involve the mesentery with adenopathy. Yersinia enterocolitica, which typically affects the distal ileum and sometimes mimics Crohn’s disease, may show enlarged nodes in the RLQ.133 Mycobacterium avium complex (MAC) often infects the intestines in an HIV patient with a CD4 cell count of 50/ mL or less and may demonstrate massive mesenteric adenopathy.105 Approximately 80% of the nodes infected with MAC are of homogeneous soft tissue attenuation; 20% show low central attenuation (see Fig. 47-35). Whipple’s disease is a systemic infection of the grampositive bacillus Tropheryma whippelii, which typically infects the small intestine, causing malabsorption. Whipple’s disease can demonstrate enlarged nodes with central low density, thought to be caused by high fat content. These nodes have attenuation values between 10 and 20 HU.35 GI tuberculosis (TB) is another infection frequently associated with enlarged mesenteric nodes. Tuberculous nodes also generally have a lower attenuation value (closer to that of luid or fat) and may show peripheral enhancement on CT, as opposed to malignant or inlammatory nodes, which tend to show homogeneous enhancement.82 Focal infectious processes such as appendicitis and diverticulitis may cause inlammatory changes in mesenteric fat with reactive mesenteric adenopathy75 (see Figs. 47-18 and 47-33).

CHAPTER 47 Inlammatory Disease. The mesentery is frequently involved in Crohn’s disease, and the inlammatory changes are well depicted on CT and MRI25,40,69,84 (see Fig. 47-19), including ibrofatty proliferation of the mesentery and complications such as abscess or phlegmon. Hypervascularity of the mesentery with vascular dilatation, tortuosity, and prominence of the vasa recta produce the comb sign, an indication of active inlammation. Mesenteric adenopathy is more commonly seen with Crohn’s disease than with ulcerative colitis. The adenopathy is often discrete rather than coalescent, as seen in lymphoma. Nodes can be located in the mesenteric root, mesenteric periphery, or RLQ and show homogeneous enhancement at CT. Inlammatory changes extending from the bowel into the mesentery in cases of Crohn’s disease are similar to those seen in appendicitis and diverticulitis—soft tissue stranding, luid, abscess, and sinus tracts/istulas. Celiac disease, a malabsorptive autoimmune disease of the small intestine, may rarely be complicated by cavitating mesenteric adenopathy.48 The adenopathy associated with the cavitating mesenteric lymph node syndrome of celiac disease also has low CT attenuation. The nodes may appear as luid or fat attenuation similar to that described in Whipple’s disease, TB, or MAC infection. However, lymph nodes containing fat-luid levels are thought to be speciic for celiac disease. Histopathologic examination reveals lymph nodes with a central cavity containing chylous luid and a thin peripheral rim of ibrous material and atrophic lymph node structures. The pathogenesis of this phenomenon is poorly understood but is theorized to result from chronic excessive antigenic exposure of the immune system to the damaged intestinal mucosa, resulting in depletion of cellular lymph node elements. Alternatively, cavitary nodal changes may relect a disturbance of the usual mesenteric lymphatic drainage.

Neoplastic. Tumors of bowel origin may involve the mesentery by multiple pathways: direct extension, lymphatic extension, nodal metastasis, and intraperitoneal seeding. GI carcinoid tumor is the most common malignant neoplasm of the small intestine, arising from neuroendocrine cells in the intestinal mucosa or submucosa, most often occurring in the distal ileum. Approximately 40% to 80% of GI carcinoids spread to the mesentery, either by direct extension or through local lymphatics.16,104 At CT the mesenteric mass is typically detected irst, manifesting as an enhancing soft tissue mass with linear bands radiating in the mesenteric fat (see Fig. 47-20). Calciication is evident in the mesenteric mass in 70% of

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cases. The radiating soft tissue bands represent ibrosis and desmoplasia caused by serotonin and other hormones secreted by the primary bowel tumor. Fibrosis in the mesentery may create a “spoke-wheel” or “sunburst” arrangement of mesenteric vessels. The desmoplastic reaction may also cause angulation and kinking of the small bowel, sometimes termed a hairpin turn. Additionally there may be associated thickening of adjacent small bowel loops secondary to tumor iniltration or caused by ischemia due to sclerosis of mesenteric vessels or lymphatic blockage.121 Extensive mesenteric disease may produce miliary implants, large masses, or mesenteric caking. The primary tumor, in contrast, is small (usually 5 mm) lesions—some of which are calciied—as well as thickening of mesenteric leaves and loss of normal mesenteric coniguration is thought to be more commonly seen in patients with TB peritonitis than with carcinomatosis. Lymph node distribution is nonspeciic, although calciication involving lymph nodes is thought to be more associated with TB. Ascites is commonly seen in both, but the amount of ascites is thought to be less with TB than carcinomatosis.42,79 Abdominal actinomycosis is a severe peritoneal infection that can also involve the mesentery. Presence of a long-standing intrauterine device is a known risk factor in young women. On CT, multiple solid

or encapsulated peritoneal and mesenteric masses that demonstrate enhancement may be seen (see Fig. 47-48). These masslike lesions represent abscesses that contain Actinomyces israelii. Resolution of these masses is seen over several weeks after antibiotic treatment.68 Peritoneal seeding of malignancy occurs most notoriously from ovarian cancer (Fig. 47-62).74 GI tract malignancy (Fig. 47-63) and pancreatic and biliary cancer commonly spread into the peritoneum and result in peritoneal carcinomatosis.11,90 Occasionally extraabdominal malignancy can metastasize to the peritoneum. A good example of this is breast cancer. Regardless of the primary tumor, the end result of peritoneal carcinomatosis has similar radiologic indings: ascites, serosal implant of tumor, omental caking, and marked enhancement of the thickened peritoneum, which is most strikingly seen on enhanced MRI. Some forms of lymphoma, notoriously effusion lymphoma, involve the peritoneum and show exactly the same radiologic indings as peritoneal carcinomatosis. This is called peritoneal lymphomatosis. Malignant peritoneal mesothelioma arises from the mesothelial cells lining the serosal surfaces of the peritoneal cavity. Radiologically this tumor is indistinguishable from typical peritoneal carcinomatosis (Fig. 47-64). Histologically it is also challenging to distinguish this tumor from peritoneal carcinomatosis due to adenocarcinoma. Often Text continued on p. 1530

A

B

FIG 47-59 Focal bacterial mesenteritis. A to C, Three consecu-

C

A

tive axial CTs of the abdomen show marked focal fat stranding in the mesentery (arrows) resembling epiploic appendagitis, following partial ileocolic resection for active Crohn’s disease. A right psoas abscess (arrowhead in C) is also complicated.

B

FIG 47-60 Bacterial peritonitis. A to C, Three consecutive axial

C

CTs through the abdomen show moderate fat stranding in the greater omentum (white arrows) and ascites as a complication of peritoneal dialysis. Note enhancement of the peritoneum (arrowheads) and peritoneal dialysis catheter (black arrow in C) in the RLQ.

CHAPTER 47

A

B

C

D

E

Mesentery

F FIG 47-61 Tuberculous peritonitis. Axial (A to D) and coronal reformatted (E and F) CTs of the abdomen and pelvis depict a large amount of ascites with iniltration in the omentum (arrows) and mesentery. Uniform thickening of the peritoneum is noted (arrowheads).

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CT and MR Imaging of the Whole Body

B

C FIG 47-62 Peritoneal carcinomatosis. A to C, CTs at three consecutive levels of the abdomen and pelvis show omental caking (white arrow) and nodular tumor implantation onto pleats of mesentery (arrowheads). Moderate ascites and enhancement of parietal peritoneum (black arrows) are also noted.

CHAPTER 47

A

Mesentery

B

C

D FIG 47-63 Pseudomyxoma peritonei with appendiceal mucocele. Axial CT (A to C) and coronal reformatted CT (D) of the abdomen and pelvis show a small amount of ascites with iniltration in the mesentery (arrows). Appendix is enlarged with thin wall calciication (arrowheads).

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A

B

C

D FIG 47-64 Peritoneal malignant mesothelioma. A to D, Axial CTs of the abdomen show omental caking (arrows) with a small amount of ascites (arrowheads). Uniform thickening of the peritoneum is noted.

open biopsy is needed for a correct diagnosis. The majority of patients have had exposure to asbestos. Therefore it is often associated with pleural manifestations of asbestos, such as pleural calciications, pleural thickening, and pleural effusions.121

Systemic Origin Systemic diseases affect the mesentery in many ways. Generalized anasarca due to any cause (e.g., congestive heart failure, septicemia, terminal cases of malignancy) causes edematous change of the mesentery. Mesenteric edema may also be associated with liver cirrhosis, nephrosis, vasculitis, or luid overload.93 An increased bleeding tendency may cause mesenteric hematoma. Lymphoma is the most common malignant neoplasm to affect the mesentery. Involvement of the mesentery by lymphoma is seen commonly with non-Hodgkin’s lymphoma in more than 50% of patients at the time of presentation. Approximately 30% to 50% of cases of non-Hodgkin’s lymphoma spread to mesenteric lymph nodes, which commonly extend from retroperitoneal involvement.141 Enlarged nodes in lymphoma can present with three patterns of involvement: in the mesenteric root, scattered throughout the peripheral mesentery, or mixed root-peripheral pattern.141 The lymph nodes may be small and discrete in early lymphoma but may progressively coalesce to form a conglomerate soft tissue mass (see Fig. 47-31). Lymphoma is a soft tumor that tends to grow around and displace normal anatomic structures such as bowel or vessels. These lympho-

matous mesenteric masses may calcify after treatment of lymphoma. Calciication is rare without treatment (120 milliseconds) on T2-weighted images, particularly with prolonged TE. Complex hemangiomas may have heterogeneous signal on T1- and T2-weighted images owing to the amount of ibrosis and hemorrhage present and the variation in size of the blood-illed spaces. After IV administration of gadolinium, splenic hemangiomas demonstrate peripheral enhancement with progressive central illing.33,89 Ramani and associates found that 19 of 22 hemangiomas had peripheral enhancement with centripetal ill-in.89 Only two lesions in their series demonstrated a clearly deined peripheral nodular type of enhancement, typically seen in hepatic hemangiomas; the remaining lesions demonstrated a peripheral rim of variable

thickness with irregular inner margins. On delayed images, splenic hemangiomas also demonstrate retention of contrast material on delayed images, like hepatic hemangiomas. However, as described for CT, not all splenic hemangiomas have this classic pattern of enhancement on MRI. Differentiation of splenic hemangioma from other splenic neoplasms can be dificult, particularly in larger lesions complicated by hemorrhage or thrombosis.30 A positive result on a nuclear medicine– tagged red blood cell scan can establish the diagnosis of hemangioma of the spleen by demonstrating increased activity on delayed images.25,57,125

Lymphangioma and Lymphangiomatosis. Lymphangiomas are rare, slow-growing, benign tumors composed of lymphatic vessels. No consensus has been reached regarding the pathogenesis of lymphangioma; however, some theories have posited that it could result from splenic lymphatic tissue agenesis or congenital malformation with obstruction.3,108 Splenic lymphangiomas are considered very rare, mostly occurring in children.1,33 These lesions may be solitary but more often appear as multiple thin-walled, well-marginated cysts that may be subcapsular in location.86,122 Splenic lymphangioma is typically an asymptomatic incidental inding; however, it may also present as a large mass with symptoms associated with mass effect on adjacent tissue.111 Diffuse lymphangiomas are called lymphangiomatosis. The prognosis of isolated splenic lymphangioma or lymphangiomatosis is believed to be good. In some cases, however, the presence of splenic lymphangiomatosis may signal multisystem involvement, known as cystic angiomatosis, consisting of lymphangiomatous or hemangiomatous involvement of bones, soft tissues, and viscera. This multisystem form may be progressive and have a poor prognosis.122 On CT and MRI, splenic lymphangiomas appear as multiloculated cystic lesions that do not enhance on arterial- or delayed-phase imaging52 (Fig, 48-7). Typically the lesions are in a subcapsular location where the lymphatics are normally concentrated.1 The lesions usually have water density on CT and follow water signal on MRI: low T1 signal intensity and high T2 signal intensity. However, if there is hemorrhage or proteinaceous debris, they can have high T1 signal intensity. Occasionally, peripheral calciications can be present. Angiography demonstrates multiple well-deined avascular lesions of various sizes that give the spleen a “Swiss cheese” appearance.

Hamartoma. Rare lesions, splenic hamartomas are usually solitary masses. They are classiied based on the predominate histologic tissue—white or red pulp—though most are a mixture of the two cell types.89 They can be cystic or solid and may have punctate or stellate calciications. Rarely these tumors are symptomatic, causing splenomegaly, pancytopenia, fatigue, and anorexia, likely due to sequestration of hematopoietic cells.17,115 Multiple splenic hamartomas may be associated with systemic hamartomas, such as with tuberous sclerosis or Wiskott-Aldrich syndrome. The imaging appearance on noncontrast CT images is a welldeined hypo- to isodense lesion that demonstrates uniform delayed enhancement that is hypo- to isodense to the spleen. The only inding may be a contour abnormality. On MRI the solid lesions may be isointense on T1- and hyperintense on T2-weighted images relative to the spleen. Unlike hemangiomas, however, hamartomas do not demonstrate an increase in signal intensity similar to that of cerebrospinal luid when images with higher T2 weighting (TE = 120-150 milliseconds) are obtained.115 After IV administration of a contrast agent, hamartomas demonstrate diffuse heterogeneous enhancement on early postcontrast images, with more uniform enhancement on delayed postcontrast images.

CHAPTER 48

A

B

C

D

E

F

Spleen

FIG 48-5 Cysts. A, CT noncontrast examination demonstrates a low-attenuation cyst with minimal peripheral calciication (arrow). B, Contrast-enhanced CT demonstrates multiple low-attenuating cysts within the dome of the liver (arrows). MRIs in a different patient show a lobulated cyst with increased signal on axial (C) and coronal (D) T2 HASTE images (arrows). E, T2 fat-saturated axial image in the same patient shows increased signal in the same lobulated cyst. F, A fat-saturated gradient echo T1-weighted image shows water signal within the cyst (arrow).

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PART II CT and MR Imaging of the Whole Body

A

B

C

D

E

F

G

H FIG 48-6 Hemangiomas. A, Axial CT image showing a low-attenuating hemangioma (arrow). B, Axial T2-weighted image showing increased signal within the same lesion (arrow). T1-weighted postcontrast axial images showing minimal enhancement at 70 seconds (C) with complete enhancement and retention of contrast at 8 minutes (D) (arrows). In a different patient, CT examination (E) demonstrates multiple small low-attenuating hemangiomas that are bright on T2 HASTE axial images (F). G and H, MR postgadolinium images at 20 seconds and 3 minutes demonstrate progressive peripheral enhancement.

CHAPTER 48 Spleen Hamartomas may be dificult to distinguish from malignant lesions. Splenic hamartomas may demonstrate radiotracer uptake on sulfur colloid scintigraphy, which may be helpful in differentiating these lesions from malignant neoplasms and hemangiomas.115

Littoral Cell Angioma. Littoral cell angiomas were irst described by Falk and colleagues in 1991 as splenic vascular tumors originating from the littoral cells of the splenic red pulp, typically appearing as multiple diffuse nodular masses within the spleen.28 These lesions are usually

1545

benign.56 Patients present with splenomegaly and symptoms of hypersplenism. On noncontrast CT the nodular masses can appear iso- or hypodense. With contrast enhancement the masses can appear hypoattenuating in the early portal venous phase and homogeneously isodense in the late portal venous phase30,38,57 (Fig. 48-8). On MRI, littoral cell angiomas demonstrate low signal intensity on T1- and T2-weighted images because of cytoplasmic hemosiderin accumulation from the phagocytic action of the littoral cell.56

Infections and Diffuse Diseases Abscess

FIG 48-7 Axial CT image of a subcapsular low-attenuating lesion found to be a lymphangioma (arrow).

A

Bacterial. Splenic abscesses are uncommon, having been reported in 0.14% to 0.70% of large autopsy series.7,15,16 The observed rise in their incidence is believed to be due to an increase in the number of immunocompromised patients, such as oncology patients undergoing aggressive chemotherapeutic regimens, critically ill patients in intensive care units, and HIV-infected patients.24 Development of a splenic abscess may require both bacteremia and intrinsic splenic disease that alters the splenic architecture, such as infarct, hematoma, or sickle cell disease. Alternatively, splenic abscess can result from direct extension of infection from adjacent organs such as the pancreas61 or stomach.54 Aerobic organisms account for 57% of splenic abscesses, with the majority being caused by Staphylococcus species, Escherichia coli, and Salmonella species; 26% of abscesses are caused by fungi, predominantly Candida species, and 18% by anaerobic organisms.77 Mortality rates range from 15% in otherwise healthy patients with unilocular splenic abscess to 80% in immunocompromised patients with multiple abscesses.4 On cross-sectional imaging, splenic abscesses may be solitary or multiple (Fig. 48-9). CT is the study of choice. Solitary abscesses and multiloculated abscesses tend to be bacterial. Septations may be present, and there may be an enhancing capsule. The CT appearance of an abscess may overlap with that of an infarct, hematoma, or neoplasm. The lack of mass effect helps differentiate infarct from abscess or tumor. The presence of gas within the lesion is diagnostic of abscess; however, this inding is rare. Gas is more readily apparent on CT than

B FIG 48-8 Littoral cell angioma. Arterial phase (A) axial CT image shows a central hypodense lesion with peripheral enhancement, which becomes isodense on the late portal venous phase (B) (arrows).

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PART II CT and MR Imaging of the Whole Body

A

B

C

D

E FIG 48-9 Abscess. A and B, Axial and coronal CT images show multiple ill-deined hypodense abscesses with some locules of air. C, Axial CT of a dominant ill-deined hypodense abscess. D and E, Multiple small low-attenuating microabscesses within the spleen in patient found to be infected with Bartonella henselae.

CHAPTER 48 Spleen on MRI (see Fig. 48-9). Percutaneous splenic abscess drainage has been described as a safe and effective procedure.67,130 Zerem and Bergsland recommend that abscesses drained percutaneously be larger than 5 cm, be unilocular or at most bilocular, have a discrete wall, and preferably be in the periphery of the midpole or lower pole of the spleen; surgical treatment should be considered for multilocular abscesses or spleens with more than two collections.130 If the abscess is less than 5 cm, only aspiration is performed. If this is not successful, drainage is attempted. In their series, Zerem and Bergsland treated 36 patients with splenic abscess with percutaneous aspiration, percutaneous drainage, or both; they had a success rate of 89% (32 of 36).130 Four patients died of predisposing factors, not the abscess itself. Despite these encouraging results, percutaneous drainage of splenic abscess should be reserved for selected patients and performed with appropriate surgical backup. When performing splenic abscess drainage, we try to traverse as little normal splenic parenchyma as possible to avoid bleeding. Fungal. Multiple small splenic abscesses (microabscesses) are typically nonbacterial in origin and are most commonly associated with fungal infections. The liver is usually involved as well. Fungal infections occur primarily in neutropenic patients, most commonly in those with acute leukemia or other lymphoproliferative disorders who are undergoing high-dose chemotherapy with or without bone marrow transplantation.95,101 An increase in the incidence of fungal abscesses of the spleen has resulted from widespread use of aggressive chemotherapy.77 Before the development of helical CT and current MRI techniques, it was dificult to establish the diagnosis of hepatosplenic candidiasis. The lesions were often undetectable because of their small size, the often nonspeciic clinical signs and symptoms, and the commonly negative results of blood culture.65,95 Percutaneous needle biopsy may also yield a false-negative result.81 Typically the lesions of hepatosplenic candidiasis are smaller than 2 cm, usually measuring 5 to 10 mm in diameter; however, they may also be less than 5 mm (miliary). On CT they often have low attenuation, although there can be a focus of high attenuation or a “wheel-within-a-wheel” pattern. MRI is the modality of choice to evaluate for hepatosplenic candidiasis. Semelka and colleagues described the appearance of hepatosplenic candidiasis on MRI and distinguished the acute, subacute, and chronic phases of infection.101 They described acute microabscesses as small (2 years) after surgery.360 Also, gastric cancers arising in the cardia were prone to anastomotic recurrence.647 Because barium studies are

CHAPTER 50

Gastrointestinal Tract

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N

A

B FIG 50-45 Advanced gastric adenocarcinoma. A, CT scan shows eccentric gastric mass (arrows) with extensive metastatic lymphadenopathy (N). B, FDG PET shows extensive extent of gastric tumor, without discrimination of metastatic lymph node from primary tumor.

B

A

FIG 50-46 Advanced gastric adenocarcinoma with peritoneal seeding. A, CT scan of the pelvis shows suspicious peritoneal seeding nodule at rectovesical pouch (arrows). B, This lesion (arrows) shows strong hot uptake at FDG PET scan, indicating the presence of deinite malignant seeding nodule.

associated with dificulty in their capability to fully assess the areas mentioned earlier, CT plays an important role in determining the extent of local tumor recurrence or distal metastasis. On CT, recurrence at the gastric stump or anastomosis appears as a localized wall thickening or mass (Figs. 50-47 and 50-48). Afferent loop syndrome may be caused by development of the recurrent tumor near the oriice of the afferent loop (Fig. 50-49). However, potential sources of erroneous interpretation include improperly opaciied bowel loop, food, surgical plication, gastritis, and gastritis cystica polyposa.291 The most frequently involved lymph nodes are those along the common hepatic artery, the celiac axis, and the hepatoduodenal ligament.291 The presence of lymphadenopathy along the hepatoduodenal ligament may cause moderate to severe biliary tract obstruction. When the pancreas is involved, CT features are indistinguishable from those of primary pancreatic tumor, and enlarged peripancreatic lymph nodes can mimic tumor recurrence in the pancreas. Most tumor recurrences at the abdominal incision are caused by iatrogenic dissemination of cancer cells during surgery (Fig. 50-50).137 However, postoperative ibrosis, hematoma, abscess, or granuloma

G

FIG 50-47 Local recurrence of gastric adenocarcinoma at the anastomotic site following subtotal gastrectomy. The bowel wall (arrows) at the surgical anastomosis is thickened and markedly enhanced along with marked distention of the remnant stomach (G).

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PART II CT and MR Imaging of the Whole Body

M

FIG 50-50 Tumor recurrence at the incisional wound after surgery for FIG 50-48 Tumor recurrence at the surgical plication. CT scan shows prominent surgical plication (arrowheads). Surgery conirmed tumor iniltration at the plication. (From Ha HK, et al: Local recurrence after surgery for gastric carcinoma: CT indings. AJR Am J Roentgenol 161:975–977, 1993.)

gastric cancer. CT scan shows a lobulated well-enhancing mass (M) along the incisional wound, as well as a large amount of ascites and peritoneal thickening due to peritoneal carcinomatosis. (From Ha HK, et al: Local recurrence after surgery for gastric carcinoma: CT indings. AJR Am J Roentgenol 161:975–977, 1993.)

A A M M

FIG 50-49 Afferent loop syndrome due to obstruction at the proximal

FIG 50-51 Gastric lymphoma. Gastric wall is markedly thickened (M)

afferent loop (A) by recurrent tumor (not shown).

with predominant involvement of the submucosa. The mucosal layer is well preserved.

cannot be differentiated from tumor recurrence at this site by imaging indings alone. Because tumor recurrences were most common within 2 years after surgery, follow-up CT scanning in a short interval is required at this period for early diagnosis.

Megibow’s group, gastric wall involvement can be divided into three patterns, as seen with CT570: 1. Diffuse iniltration involving more than 50% of the length of the stomach 2. Segmental iniltration 3. The localized polypoid form Gastric wall thickening is most commonly circumferential, with thickness greater than 4 cm. Thickening and distortion of the gastric rugal folds may be present, but outlet obstruction is rare (Fig. 50-51).100,570 Dynamic CT and MRI clearly depict submucosal spread of the tumor within the normally enhanced mucosal layer (Fig. 50-52).587 Lymphomatous tissues in the thickened gastric wall usually show poor and homogeneous contrast enhancement; this pattern may be due to lack of desmoplastic response in lymphoma, in contrast with gastric adenocarcinoma. Sometimes gastric lymphoma shows heterogeneous enhancement. In such cases the hypoattenuated areas may be caused by pathologic evidence of necrosis and hemorrhage.319 The localized polypoid form

Lymphoma. The stomach is the most frequent site of lymphomatous involvement of the GI tract. Non-Hodgkin’s lymphoma accounts for approximately 80% of cases. Gastric involvement may be isolated but more commonly is part of a generalized disease process. Among various prognostic factors that include gender, age, size and location of tumor, histologic type, depth of invasion, and nodal status, depth of invasion and regional lymph node involvement play a decisive role in survival.88 Unlike carcinoma, lymphoma tends to spread laterally within the submucosal plane and spares the muscular coats until late in its course. With its ability to directly image the entire gastric wall and adjacent structures, CT has proved capable of determining the extent of spread of gastric lymphoma with a high degree of accuracy.100 According to

CHAPTER 50

Gastrointestinal Tract

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M M

A

B

M

M

C

D FIG 50-52 Gastric lymphoma. A, A mass (M) is seen in the gastric wall along the lesser curvature of the stomach on CT scan. B, T2-weighted MRI shows a mass (M) with intermediate signal intensity. C and D, Dynamic Gd-enhanced MRI shows poor contrast enhancement of the mass (M) in the early phase (C) and isointensity to that of the liver in the delayed phase (D).

is often associated with an ulcer. The perigastric fat plane is usually preserved. Most patients with gastric lymphoma have perigastric lymphadenopathy, and the presence of widespread retroperitoneal lymphadenopathy indicates systemic disease. Perforation is an important complication affecting therapy and prognosis. It may occur in 9% to 47% of patients as a result of the lack of desmoplastic response, rapid growth of the tumor, or a response to therapy. Tumor extension into the esophagus is present in about 10% of patients, and spread across the pylorus into the duodenal bulb has been noted in approximately one third of patients.339 Although not common, far-advanced cases of lymphoma can show diffuse peritoneal involvement with ascites, omental iniltration, and peritoneal implants, mimicking carcinomatosis (Fig. 50-53).403

Gastrointestinal Stromal Tumor. GISTs are the most common nonepithelial neoplasms of the stomach and small bowel. Although GIST accounts for only 2.2% of malignant gastric tumors, most GISTs are located at the stomach (60%-70%) and small intestine (20%-30%). GISTs are now thought to be derived from a precursor of the interstitial cells of Cajal and are clearly different from other mesenchymal tumors such as leiomyomas or leiomyosarcomas.617 Almost all GISTs express activating mutations in the KIT gene, which encodes transmembrane receptor tyrosine kinase in the interstitial cells of Cajal, and

result in promoting tumor growth. Therefore identiication of KIT protein (CD117, stem cell factor receptor) is a key in conirming diagnosis of GISTs and improves clinical expectation of long-term survival by using imatinib (a targeted tyrosine kinase receptor blocker). Unlike leiomyoma, no GIST can truly be labeled benign.166 Even GISTs smaller than 2 cm, generally considered benign, show a very low risk of recurrence. In addition to early detection of the tumor, therefore, monitoring for therapeutic response or tumor recurrence becomes more important. CT is the main imaging modality for these purposes. CT features of GISTs vary greatly depending on the size and aggressiveness of the tumor. Most primary GISTs are large, hypervascular, enhancing masses on contrast-enhanced CT; 90% are located in the fundus and body, and their growth is exogastric or dumbbell shaped.569 Dynamic CT may demonstrate their submucosal location by showing the intact mucosal layer enhancement (Fig. 50-54). Small localized GISTs are usually homogeneous, whereas larger tumors are heterogeneous on CT, with common occurrence of low-attenuated areas owing to internal hemorrhage, necrosis, or cystic changes (Fig. 50-55)133,707; the presence of hemorrhage produces a luid-luid level within the mass. Areas of necrosis can give the appearance of multiple thick septations within the tumor. Necrosis within the tumor mass may lead to excavation and communication with the GI tract or perforation into the peritoneal cavity.

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FIG 50-53 Peritoneal lymphomatosis. CT scan shows omental cake

In one series,737 crescent-shaped necrosis due to necrosis in the periphery of the extraluminal component of the mass was reported to be suggestive of a stromal tumor on CT. Ulceration of the overlying mucosa can be demonstrated on CT as the presence of air or an oral contrast agent. Another cause of gas within the mass may be superinfection of the necrotic tumor (Fig. 50-56).768 Although not common, calciication is seen in stromal tumors (Fig. 50-57). Nearly 50% of patients with GISTs present with metastases615; the most common sites are the liver and peritoneum, followed by lung and bone (Fig. 50-58). Unlike in adenocarcinoma, lymphatic metastases or malignant ascites of GISTs are extremely rare. CT characteristics of metastatic lesions of GISTs are similar to those of primary GISTs. Histologic assessment of malignancy is essentially based on mitotic counts and size of the tumor. In general, tumors less than 5 cm and with fewer than 5 mitoses per 10 high-power ields (HPF) suggest lowgrade malignancy. However, tumors greater than 5 cm with higher than 5 mitoses/10 HPF are considered high-grade malignancy. CT

(arrows) and diffuse mesenteric iniltration.

m

FIG 50-56 Infected malignant GIST of the stomach. CT scan shows a FIG 50-54 Malignant GIST. CT scan shows a large heterogeneous mass (m) growing exophytically from the stomach (arrow).

large heterogeneous mass (arrows) with central cavitation and gas collection. The small oriice of the ulcer in the tumor was considered to be the cause of secondary infection.

M

M

FIG 50-55 Malignant GIST. Huge exophytic growing mass (M) arising from the gastric high body is seen, with severe central necrosis. Note intact overlying mucosal layer enhancement (arrow).

FIG 50-57 Benign GIST of the stomach. A calciied mass (M) (arrow) is seen at the gastric high body.

CHAPTER 50

Gastrointestinal Tract

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m m

m

m

m M

A

B FIG 50-58 Malignant GIST of the stomach with distant metastases. CT scan shows hepatic metastasis (M) (A) and multiple peritoneal seeding masses (m) (B). Little lymphadenopathy is seen in the abdominal cavity.

A

B FIG 50-59 Metastasis to the stomach (linitis plastica) from breast cancer. A, Double-contrast upper GI series shows focal luminal narrowing (arrows), rigidity, and fold thickening in the proximal antrum and lower body of the stomach. B, CT scan shows involvement of the stomach by a scirrhous tumor (arrows).

features favoring malignancy of GISTs include tumor size larger than 5 cm, ulceration, heterogeneous enhancement with necrosis or hemorrhage, and distant metastases. During treatment with imatinib, therapeutic response is demonstrated by decreased tumor size, rapid transition from a heterogeneously hyperattenuating pattern to a homogeneously hypoattenuating pattern, resolution of the enhancing tumor nodules, and decreased intratumoral vessels. On the other hand, development of an enhancing nodule within the treated tumor suggests tumor recurrence regardless of changes in tumor size.20,128

Metastatic Tumor. Hematogenous metastases may be discovered during abdominal CT performed for other reasons. Malignant melanoma and breast and lung carcinoma are the usual primary lesions. Metastasis from a lobular carcinoma of the breast produces a linitis plastica pattern of gastric wall thickening (Fig. 50-59).115 Squamous carcinoma of the esophagus reportedly involves the gastric cardia in up to 15% of patients and may simulate a primary mucosal or submucosal neoplasm.258 Carcinomas of the transverse colon and tail of the pancreas metastasize to the gastric wall by direct extension via the gastrocolic and splenorenal-gastrosplenic ligaments, respectively.

Liposarcoma. Gastric liposarcoma originates in undifferentiated mesenchymal cells present within the submucosa and tunica muscularis of the gastric wall.459 Pathologically, four forms are recognized: (1) differentiated, (2) myxoid, (3) round cell, and (4) pleomorphic. Exuberant exophytic growth explains the lack of speciic GI symptoms and delayed diagnosis. CT appearances correlate with the macroscopic appearance of the neoplasm. Fatty areas within the tumor are reported only in the differentiated form.516 Undifferentiated liposarcomas commonly contain areas of necrosis and hemorrhage along with prominent enhancement of the solid zones.213 Myxoid tumors present as a cystic form owing to the presence of gelatinous matrix.213

Plasmacytoma. Malignant neoplasms of plasma cells (plasmacytoma) appear in two forms. The diffuse form includes multiple myeloma or plasma cell leukemia; the local form is a solitary myeloma of bone or an extramedullary plasmacytoma. Ten percent of cases of extramedullary plasmacytoma occur in the GI tract; the small bowel is most commonly involved, followed by the stomach, colon, and esophagus. Primary gastric plasmacytoma accounts for approximately 5% of all extramedullary plasmacytomas.

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PART II CT and MR Imaging of the Whole Body

The diagnosis of primary gastric plasmacytoma is established by the absence of a serum M protein component; hence there is no Bence Jones proteinuria, no bone marrow iniltration, and no visceral involvement other than of the stomach.757 Pathologically, primary gastric plasmacytoma has been thought to originate from lymphoid follicles in the submucosa or from plasma cells in the lamina propria of the mucosa and can have various forms. Remingo and Klaum grossly classiied gastric plasmacytoma into four types: (1) nodular, (2) iniltrative, (3) ulcerative, and (4) polypoid721; the nodular type was most commonly seen in their study. CT indings of gastric plasmacytoma simulate those of lymphoma or a mucinous type of gastric cancer owing to poor contrast enhancement of the gastric wall (Fig. 50-60).907

A

Deep endoscopic biopsy combined with immunohistochemical study of immunoglobulin is essential in diagnosis.780

Inlammation and Other Conditions Peptic Ulcer Disease. Although CT has no useful role in patients with uncomplicated peptic ulcer disease, it is effective in detecting its complications (e.g., acute free perforation, penetration). The ulcers are frequently identiied on CT as round thin-walled collections of air or orally administered contrast medium projecting beyond the conines of the gastric or duodenal lumen. Although direct visualization of the ulcer may be dificult on CT in many instances, the involved gastric or duodenal wall is mostly thickened with considerable mural edema (Figs. 50-61 and 50-62). If free perforation is present, CT may show

B FIG 50-60 Gastric plasmacytoma. A, Upper GI radiograph shows large gastric mass (arrows) with a sharply marginated border. B, CT scan shows marked gastric wall thickening (arrows) with poor contrast enhancement, simulating lymphoma or adenocarcinoma. (From Yoon SE, et al: Upper gastrointestinal series and CT indings of primary gastric plasmacytoma: Report of two cases. AJR Am J Roentgenol 173:1266–1268, 1999.)

U

L

U

A

B FIG 50-61 Benign gastric ulcer. A, A large penetrating ulcer (U) is seen in the posterior wall of the stomach, with markedly enhancing inner layer of the thickened gastric wall and edematous outer layer (arrows). Minimal perigastric iniltrate is also seen. A lipoma (L) is incidentally found in the duodenum. B, Doublecontrast upper GI series shows a large ulcer crater (U) with convergence of thickened gastric wall.

CHAPTER 50

Gastrointestinal Tract

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A

P

FIG 50-62 Benign gastric ulcer. The swollen gastric wall surrounding

FIG 50-63 Conined peptic ulcer perforation. CT scan shows a perigas-

the gastric ulcer simulates a polypoid mass (P). Gastric wall thickening (arrows) is also present.

tric cystic mass (A) with a thick peripheral wall in the perigastric region. The wall of the stomach and duodenum is considerably thickened, with heterogeneous contrast enhancement (arrows) and evidence of perigastric iniltrates.

free extravasation of oral contrast material or free intraperitoneal air, or both, along with evidence of diffuse peritonitis such as omental or mesenteric iniltration and intraperitoneal luid collection. Although CT is not very accurate in detecting the perforating site,363,531 the use of thin-section spiral CT may improve detection by demonstrating interruption of the well-enhanced gastric wall.629 On occasion, peptic ulcers that extend beyond the serosa of the bowel wall may penetrate adjacent structures (conined perforation or penetration). The most common site of penetration is the pancreas, owing to an ulcer’s proximity to the distal stomach and duodenum and ixation of its position.531 Other sites include the gastrohepatic omentum, biliary tree, and liver, with the omentum being involved by gastric ulcers and the biliary tree by duodenal ulcers.313 On CT the diagnosis of ulcer penetration can be conirmed when a low-density linear band (sinus tract) containing perigastric contrast material is identiied or when an ectopic pocket of gas is demonstrated in the perigastric space adjacent to the suspected ulcer crater (Figs. 50-63 and 50-64). In cases of pancreatic penetration, the fat plane between the ulcer and the pancreas is lost and the pancreas is focally enlarged with diminished CT attenuation, indings indistinguishable from those of acute pancreatitis. However, despite pancreatic enlargement, the remaining peripancreatic fat plane is commonly preserved, and only a small number of patients may show an increased level of serum amylase or lipase in such instances.363 CT can also depict penetration of a gastric ulcer crater or its surrounding inlammatory mass into the splenic parenchyma.257

Gastritis and Other Conditions Causing Gastric Wall Thickening. Gastritis, recently associated with Helicobacter pylori infection, commonly involves the antrum and body of the stomach, with most cases involving the antrum.851 Enlargement of gastric folds and thickening of the gastric wall may be due to to a combination of mucosal inlammation, submucosal edema, and secondary hypertrophy and hyperplasia of the gastric mucosa. Gastritis appears as circumferential or focal gastric wall thickening on CT.851 Although CT is sensitive in detecting inlammatory processes in the stomach, it is not speciic in differentiating gastritis from gastric malignancy. Absence of obliteration of the fat planes, perigastric iniltration, and lymphadenopathy may aid in diagnosis. Other infectious processes such as toxoplasmosis and cryptosporidiosis can also cause nonspeciic gastric wall thickening.804,808

D

FIG 50-64 Conined duodenal ulcer perforation. CT scan shows edematous bowel wall thickening of the duodenum (D) with an ulcer crater (arrow). A small amount of luid is collected in the paraduodenal space.

In rare instances of acute infectious gastritis, an intramural gastric wall abscess develops, simulating a submucosal tumor.144 In patients with emphysematous gastritis, CT may show an irregular thickened gastric wall along with multiple intramural gas bubbles. When intramural gas is seen with noninfectious causes of gastric emphysema (e.g., secondary to gastric outlet obstruction), the gas is distributed as thin uniform linear streaks.548 Although rare, chronic granulomatous disease can involve the stomach, especially along the antrum, with diffuse nonspeciic gastric wall thickening on CT. Ménétrier’s disease shows diffuse thickening of the gastric mucosal folds, predominantly along the body and fundus of the stomach (Fig. 50-65). In immunocompromised patients, graft-versus-host disease (GVHD) may demonstrate not only gastric wall thickening on CT but also a peculiar persistent coating of the gastric and small bowel mucosa with orally administered contrast material.377 CT also demonstrates gastric fold or wall thickening in Zollinger-Ellison syndrome (Fig. 50-66), amyloidosis, sarcoidosis, and eosinophilic gastritis. An extragastric inlammatory process (e.g., acute pancreatitis) may involve the gastric wall with focal thickening or cystic mass formation (Fig. 50-67).

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Congenital Conditions Diverticula. Gastric diverticula generally arise from the posterior wall of the fundus. They appear as a thin-walled cystic-appearing mass on CT (Fig. 50-68). If the diverticulum is not illed with air or orally administered contrast material, it simulates a cystic inlammatory or neoplastic condition of adjacent structures.

Ectopic Pancreatic Rest. The ectopic pancreas pathologically

FIG 50-65 Ménétrier’s disease of the stomach. CT scan shows marked thickening (arrows) of the gastric rugal folds along the greater curvature of gastric fundus and high body.

appears as a smooth nodule and occasionally as a mass with an irregular surface. It is usually situated in the submucosa and only occasionally expands into the muscularis. It most frequently occurs in the antrum within 3 to 6 cm of the pylorus and is on the greater curvature side of the posterior wall of the stomach; other sites include the second portion of the duodenum and the jejunum.62 On barium study, demonstration of umbilication, which represents illing of the rudimentary pancreatic duct, may suggest the proper diagnosis. When a nodule exceeds 2 cm, it appears as a mural nodule on CT (Fig. 50-69).

Gastric Duplication. Most gastric duplications occur during the

FIG 50-66 Gastric fold thickening due to gastrinoma. CT scan shows marked gastric distention and luid excess with prominent and thickened mucosal folds (arrowheads). A small mass (arrow), which was conirmed as gastrinoma at surgery, is noted in the perigastric region.

irst year of life, but 28% of cases have been detected in patients older than 12 years.694 Approximately 82% are spherical cysts and do not communicate with the stomach; the remaining 18% are tubular and communicate with the gastric lumen.883 Although rare, a pedunculated type of duplication with a thin ibrous strand is also reported.448 The most common location is along the greater curvature, followed by the posterior wall, lesser curvature, anterior wall, and pylorus. Ectopic pancreatic tissue is found in the wall of up to 37% of gastric duplications328 and is associated with pancreatitis and elevated amylase levels. Detection of associated vertebral anomalies such as spina biida, hemivertebra, and complete vertebral body cleft is a helpful clue for the diagnosis. Clinically, duplications occur twice as often in girls than in boys. Clinical symptoms and signs include a palpable mass, gastric obstruction, abdominal pain, melena, or hematemesis. Gastric duplication may undergo torsion and may perforate and cause a surgical emergency.779 CT and MRI may be used to determine the nature, size, and extent of the mass, revealing a cystic mass contiguous with the stomach and containing luid, gas, or debris. Curvilinear calciication is rarely detected on the wall of the duplication.230 The differential diagnosis with other disease entities such as pancreatic cyst and pseudocyst, mesenteric cyst, and various intramural tumors of the stomach cannot be easily made by imaging indings alone. Technetium 99m-pertechnetate may show uptake of the radiopharmaceutical agent in the gastric mucosal lining.

Other Conditions Varices. Esophageal and gastric varices develop in patients with

P

FIG 50-67 Gastric wall involvement in a patient with pancreatitis. CT scan shows a cystic mass (P) in the gastric wall due to extension of pancreatic pseudocyst.

portal hypertension as a consequence of either intrahepatic obstruction (e.g., cirrhosis) or extrahepatic obstruction (e.g., portal or splenic vein occlusion). In contrast to the supericial location beneath the mucosa in esophageal varices, gastric varices tend to have a subserosal location and are thereby easily mistaken at endoscopy or radiographic studies for other submucosal masses.113 In the stomach the posteromedial border of the gastric fundus is the most common site, although any part of the stomach can be involved. CT is a sensitive tool for detecting gastric varices and determining their primary cause. Gastric varices appear as well-deined clusters of markedly enhancing rounded and tubular lesions within the scalloped gastric wall (Fig. 50-70).113 Intraabdominal collateral venous channels may also be seen along the distribution of the left gastric, gastroepiploic, or short gastric vein.

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F

B C

A

B

C FIG 50-68 Gastric diverticulum. A, Coronal CT image shows a diverticulum (short arrow) arising from the gastric fundus (F) base, which is illed with oral contrast material. B and C, Axial CT images corresponding to the levels indicated by arrows B and C in part A show a contrast-illed outpouch (arrow) from the gastric fundus.

M

FIG 50-69 Ectopic pancreas in the stomach. CT scan shows a submucosal mass (M) in the prepyloric antrum of the stomach.

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FIG 50-71 Transient jejunojejunal intussusception after gastrectomy. CT scan shows a heterogeneous masslike lesion (arrow) in the jejunal loop caused by invagination of the regional mesentery into the bowel lumen. Small bowel follow-through study (not shown) did not demonstrate any mass.

A Although the diagnosis can be made with an upper GI series or gastroscopy, CT is also useful in diagnosis and early detection of possible strangulation in the intussuscepted jejunal loop. CT may show dilatation of the gastric remnant, with evidence of intragastric position of the jejunal loop and mesentery (Fig. 50-71).506,515

Gastric Herniation and Volvulus. The diagnosis of gastric hernia-

B FIG 50-70 Varices of the gastric fundus in a patient with liver cirrhosis. A, Double-contrast barium study of the stomach shows nodular illing defects (arrows) at the gastric fundus, which reveals a smooth mucosal surface. B, On CT scan of portal venous phase, this lesion is matched with prolonged enhancing vascular structure (arrows) within the gastric fundic wall, indicating gastric varices.

Gastroduodenal Intussusception. Gastroduodenal intussusception is an uncommon condition reported to be caused by benign pedunculated gastric tumors such as stromal tumor, adenoma, and lipoma or Ménétrier’s disease.173,299 CT indings are characteristic. The site of the invagination is seen as a target-like mass in the duodenal region. Both CT and barium study may also show foreshortening and beaklike narrowing of the distal stomach as well as gastric outlet obstruction (see Fig. 50-34).173,299

tion through the lacerated diaphragm is often delayed or missed because its plain radiographic appearance resembles that of pneumothorax, hemothorax, pleural effusion, pulmonary consolidation or collapse, or raised hemidiaphragm. In addition to penetrating or blunt trauma to the diaphragm, laxity or absence of the tethering gastric ligaments, as well as conditions that increase the size of the esophageal hiatus, such as rapid changes in intraabdominal pressure (i.e., trauma) and degenerative changes (i.e., aging), may also predispose to herniation and volvulus of the stomach. Herniation may involve the fundus only or much of the body and antrum. In this condition a nasogastric tube may show a normal position at the esophagogastric junction but then pass up into the chest, although such indings can be seen in the presence of an elevated left diaphragm. A barium study may show the intrathoracic position of the herniated stomach as well as a waistlike constriction in the stomach where the stomach passes through the diaphragm. Although CT may be suboptimal in evaluating the diaphragm, several reports acknowledge its success (Fig. 50-72).314,846 Use of additional reformatted images in the coronal or sagittal plane helps facilitate detection of diaphragmatic abnormalities. MRI, especially with coronal or sagittal T1-weighted images, is useful not only for establishing the diagnosis but also for localizing the site of lacerated diaphragm (Fig. 50-73). To determine the presence or absence of strangulation of the herniated stomach that is mainly caused by volvulus, IV infusion of contrast material in both CT and MRI is mandatory.

Jejunogastric Intussusception. Jejunogastric intussusception is a rare complication of gastric surgery that may present either in acute form or as a chronic recurrent process. According to the type of invaginated loop, it can be classiied as an afferent or efferent loop invagination or both. Efferent loop invagination is seen most commonly. Retrograde peristalsis is considered to be the main pathogenetic factor. Immediate laparotomy should be performed because an 80% mortality rate has been reported when treatment is delayed.136

Corrosive Gastric Injury. Corrosive agents produce extensive damage to the GI tract, with perforation or death occurring in the acute phase. Alkaline caustic agents produce injury by liquefaction necrosis.261 Fat and proteins become saponiied, and blood vessels are thrombosed, leading to further cellular necrosis and degeneration. This characteristic of an alkali enhances its penetration into tissues, resulting in complete dissolution of the upper GI tract and damage of

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H

S

S

A

B FIG 50-72 Delayed posttraumatic diaphragmatic hernia. A, CT scan shows herniation (H) of the proximal part of the stomach (S) into the thorax as well as evidence of disruption of the left crus of the diaphragm (arrows). B, Barium study shows gastric obstruction with markedly distended herniated intrathoracic stomach (S).

S

S

A

B FIG 50-73 Delayed posttraumatic diaphragmatic hernia. Gastric wasting (arrows) and intrathoracic position of the herniated stomach (S) are clearly depicted on coronal T1-weighted (A) and half-Fourier acquisition single-shot turbo-spin echo (HASTE) (B) MRI. Note the hyperintense thin diaphragm.

adjacent structures, even including in rare instances the transverse colon. In contrast to alkaline agents, concentrated acids produce a coagulative necrosis with a protective eschar that develops rapidly and may limit penetration to deeper muscle layers.285 The esophagus and stomach are the most common sites of involvement, but in severe cases, signiicant liquefaction necrosis can occur both extraluminally and much more distally in the GI tract, with the development of ischemia.622 Diagnostic evaluation of patients with corrosive injury should include examination of the entire esophagus, stomach, and duodenum by endoscopic or noninvasive methods. However, CT is useful in evaluating structures beyond the irst site of injury, thus avoiding the risk of instrumental perforation associated with endoscopy (Figs. 50-74 and 50-75).

DUODENUM PATHOLOGIC CONDITIONS Malignant Neoplasms Primary Adenocarcinoma. Most cases of primary duodenal carcinomas occur in the periampullary region and the third portion of the duodenum; duodenal bulb involvement is extremely rare.139 Duodenal adenocarcinoma may be associated with Gardner’s syndrome, neuroibromatosis, celiac sprue, Crohn’s disease, and Peutz-Jeghers syndrome. Lesions situated more distally usually have a napkin-ring appearance and produce partial intestinal obstruction; about 20% have

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S

A FIG 50-74 Corrosive gastritis after acid ingestion, with nearly complete loss of posterior wall of the stomach (S), as seen on this CT scan.

S

FIG 50-75 Corrosive gastritis with pneumatosis in the gastric wall and multifocal hepatic infarction. CT scan shows intramural gas (arrowheads) along with pneumoperitoneum (white arrow) and ascites due to gastric perforation. Also noted are intrahepatic portal vein gas (black arrows) caused by hepatic infarction. (From Rha SE, et al: CT and MR imaging indings of bowel ischemia according to the various primary causes. Radiographics 20:29–42, 2000.)

B FIG 50-76 Ampulla of Vater cancer. A, CT scan shows an intraluminal protruded mass with caulilower surface (arrows) in the region of the ampulla of Vater. B, This mass is well demonstrated on coronal CT image (arrows). Note the “double-duct sign” by the mass, which consists of marked dilatation of both the common bile duct (two arrows) and main pancreatic duct (thick arrow).

a predominantly polypoid or fungating appearance, probably caused by their origins in preexisting adenomatous polyps or villous adenomas (Fig. 50-76).85 Metastases are often present in the regional lymph nodes at the time of diagnosis, and thus the prognosis is poor. On CT, primary duodenal adenocarcinomas appear as an intrinsic mass with a short segment of bowel wall thickening (Fig. 50-77).206,394 The incidence of duodenal obstruction is common. Sometimes when tumors invade the pancreas and biliary ducts, it may be dificult to distinguish these tumors from pancreatic and biliary tumors. With primary adenocarcinomas, the duodenal wall is more circumferentially thickened, with a lesser degree of biliary and pancreatic duct dilation.

Lymphoma. Duodenal lymphoma is rare because the distribution of lymphoma is proportionate to the amount of lymphoid tissue. Characteristic CT features include a long segment of a large annular wall thickening along with aneurysmal dilatation of the lumen and bulky regional or more widespread lymphadenopathy (Fig. 50-78). In contrast to cases of primary adenocarcinoma, bowel obstruction is

FIG 50-77 Primary duodenal carcinoma. CT scan shows concentric bowel wall thickening (arrow), producing low-grade bowel obstruction. Note lymphadenopathy in the paraaortic and periduodenal regions.

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S

D

FIG 50-78 Duodenal lymphoma. CT scan shows irregular concentric

FIG 50-79 Duodenal obstruction caused by direct tumor invasion of

bowel wall thickening (arrows) in the duodenum. Note lymphadenopathy along the root of mesentery and lymphomatous nodules in the liver.

pancreatic cancer into the third portion of the duodenum. CT scan shows irregular soft tissue mass (arrows) obstructing the duodenum (D), with marked distention of the stomach (S). Pancreatic cancer is not shown.

uncommon. In rare instances, lymphoma involving the ampulla may produce biliary tract obstruction.

Metastatic Neoplasms. Direct invasion from tumors of the adjacent organs is the most important route for metastatic neoplasm of the duodenum. Primary tumor sites include the pancreas, stomach, gallbladder, liver, bile tract, right colon, and right kidney. In metastatic pancreatic or bile duct tumor, the medial aspect of the C-loop is involved, with eccentric duodenal wall thickening. On the basis of CT indings alone, however, it may be dificult to ascertain whether the enguling mass is of duodenal, bile duct, or pancreatic origin (Fig. 50-79). Metastases from left colon carcinoma occur via the lymphatic drainage to the central mesenteric nodes surrounding the fourth portion of the duodenum or across the short fascial plane of the lateral relection of the transverse mesocolon206; it may cause duodenal or jejunal obstruction. Hematogenous and lymphatic metastasis to the duodenum also occurs in lung and breast cancer (Fig. 50-80). In patients receiving chemotherapy for lung cancer, bowel obstruction and perforation may develop as a result of tumor necrosis in a metastatic lesion.565 Gastric cancer may spread intramurally to the duodenum through submucosal lymphatic channels.211

Other Conditions Trauma. Because a large portion of the duodenum is within the retroperitoneum, most perforations occurring in these segments are clinically insidious. The horizontal segment of the duodenum crosses the vertebral column and is easily compressed against the spine by a direct blow. The distinction of duodenal perforation from an intramural hematoma without perforation is important because the latter condition does not require surgery.501 CT is becoming the most widely used modality for patients with abdominal trauma. Identiication of extraluminal gas or extravasated oral contrast material or both in the right anterior pararenal space indicates the presence of duodenal perforation.453 Intramural duodenal hematomas are manifested on CT as tubular or ovoid, circumferential or eccentric, heterogeneous wall thickening (Fig. 50-81); a curvilinear area of high density (signet ring sign) can be demonstrated inside the margin of the hematoma.910 When the hematoma is resolved, the hematomas become cystic. Because of contiguity with the duodenum, it is important to search for an associated injury of the head of the pancreas.

M

FIG 50-80 Metastasis to the duodenum from squamous cell carcinoma of the lung. CT scan shows a polypoid mass (M) protruding into the duodenal lumen.

Pancreatitis. Inlammation in pancreatitis may spread from the pancreas at the site of direct contact with the nonperitonealized posterior surface of the second part of the duodenum.55 Once the barrier is crossed, the inlammatory process may extend along the wall of duodenum. Duodenal involvement in pancreatitis can be identiied on CT by nonspeciic wall thickening (Fig. 50-82). In rare instances, intramural duodenal pseudocyst develops561; CT attenuation in this pseudocyst is related to the presence or absence of hemorrhage, cells, or proteinaceous material. In such cases, CT differentiation of duodenal pseudocyst from duodenal duplication cyst, choledochocele, or cystic dystrophy of the duodenal wall is often dificult.

Cystic Dystrophy. Cystic dystrophy of the duodenal wall is a rare lesion characterized by the presence of cysts within the duodenal wall that originate from ectopic pancreatic tissue. This lesion can be induced

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H D

FIG 50-81 Intramural duodenal hematoma after blunt abdominal trauma. CT scan shows a sausage-like cystic lesion (H) in the wall of the duodenum.

*

FIG 50-82 Pancreatitis with secondary duodenal involvement. CT scan shows concentric bowel wall thickening of the duodenum (asterisk) with heterogeneous contrast enhancement of the enlarged head of the pancreas.

by inlammation of ectopic pancreatic tissue within the duodenal wall secondary to obstruction of pancreatic excretory ducts. Since the irst report in 1970 by Potet and Duclert,687 the radiologic appearances of this lesion have been described.693 The pancreas may appear to be normal or show evidence of chronic inlammation. In the cystic variant of cystic dystrophy, the cysts are easily demonstrated by both ultrasonography and CT between the duodenum and the pancreatic head. In contrast to a pseudocyst, the cystic variant is more frequently elongated or bilobate.693 The solid variant of cystic dystrophy is depicted as thickening of the duodenal wall along with microcysts embedded within it.693

Aortoduodenal Fistula. Aortoduodenal istula is a rare and usually fatal disease; it may be primary or secondary. Primary aortoduodenal istula is caused mainly by atherosclerotic aneurysms (>70% of cases). Other causes of aortic aneurysms complicated by aortoduodenal istula are trauma and infections (e.g., TB, syphilis, salmonellosis, mycosis).727 Although extremely rare, primary aortoduodenal istula can also occur without an associated aortic aneurysm; causes include carcinomas, irradiation, peptic ulcers, foreign bodies, cholecystitis,

FIG 50-83 Primary aortoduodenal istula in a patient with an aortic aneurysm. CT scan shows periaortic ibrosis (arrows) with subtle gas bubbles (arrowheads) in the periaortic region. The duodenal wall (D) adjacent to the aortic aneurysm is thickened, causing low-grade duodenal obstruction.

diverticulitis, and bacterial infections.440 Secondary aortoduodenal istula is generally a complication of abdominal aortic aneurysm repair. The most common sites of involvement in all types of aortoduodenal istula are the third and fourth parts of the duodenum. Clinical symptoms include abdominal or back pain, hematemesis, melena, and an abdominal pulsatile mass. Surgical therapy carries high mortality and morbidity rates, primarily because of the dificulty and delay in establishing the diagnosis. CT may offer a quick, inexpensive, and accurate method of diagnosis. On CT, an aortoduodenal istula should be considered if extraluminal gas is present in the periaortic region (Fig. 50-83). Gas may also be noted within the calciied rim of the aneurysm in association with an adherent loop of intestine. Other indings include pseudoaneurysm formation and focal bowel wall thickening. In patients who have undergone aortic reconstructive surgery, complete resolution of hematoma should occur in 2 to 3 months, and no ectopic gas should be visualized at 3 to 4 weeks.700 After that time, any amount of perigraft soft tissue, luid, or ectopic gas should be considered a sign of graft infection or aortoenteric istula. However, the differentiation between aortoenteric istula and perigraft infection is dificult, although the presence of ectopic gas favors the diagnosis of aortoenteric istula.517

SMALL INTESTINE NORMAL ANATOMY On CT, normal small bowel wall thickness measures 2 to 3 mm; a wall thicker than 4 mm is considered abnormal except in the terminal ileum, where 5 mm is considered the upper limit of normal.740 The thickness of valvulae conniventes should not exceed 3 mm. When the intestine is collapsed or partially distended, the wall may appear to be 3 to 4 mm thick. If the wall seems to be concentrically and symmetrically thickened and is homogeneously enhanced, the clinical signiicance of a thickness greater than 4 mm should be interpreted cautiously and assessed in relation to the degree of distention of the small bowel loop.33 The fat in the mesentery has the same attenuation as fat elsewhere in the body. Major arteries and veins are identiiable as branching structures within mesenteric fat and do not exceed 3 mm in diameter.365 Mesenteric lymph nodes are occasionally observed within mesenteric fat and do not exceed 3 mm in diameter.

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IMAGING TECHNIQUES Fluoroscopic examinations such as small bowel follow-through and barium enteroclysis used to be the most commonly performed radiologic tests to evaluate the small bowel. With recent advances in MDCT and fast MRI technologies, which have led to improved spatial and temporal resolution that allows exquisite high-resolution imaging of the small bowel, CT and MRI now have become the major radiologic modalities for small bowel evaluation. Compared to luoroscopic studies, which give information mostly about inside the bowel, CT and MRI have the capability of mural and extraluminal evaluation. MPR or angiographic reconstruction of CT and MRI can also sometimes provide additional diagnostic information that is dificult to obtain otherwise. Optimal distention of the small bowel by administration of oral contrast is essential for accurate CT or MRI examination. Contrast administration can be performed perorally (i.e., CT enterography or MR enterography) or by infusion via nasoenteric intubation (i.e., CT enteroclysis or MR enteroclysis), similar to the procedure for barium enteroclysis. Although enteroclysis technique theoretically provides better small bowel distention, previous studies have not clearly shown the superiority of enteroclysis technique compared to enterography technique.611,776,890 Therefore it may not be necessary to use an invasive nasoenteric intubation for CT or MR examinations of the small bowel.

CT or MR Enterography For CT enterography, neutral oral contrast that produces attenuation similar to the attenuation of water is the choice in most examinations. Positive oral contrast, which was commonly used previously to distend and opacify the bowel loops, is helpful in delineation of luminal contour, detection of ulcer or istula, and distinction between bowel loops and extraluminal structures such as mesenteric tumor or lymphadenopathy (Fig. 50-84). However, it makes evaluation of bowel wall enhancement dificult, which is a substantial drawback because bowel wall enhancement is crucial for detection and differentiation of many bowel diseases. Positive contrast also precludes 3D angiographic reconstruction of mesenteric vessels with volume rendering or maximum intensity projection (MIP) techniques because of the overlap between the contrast-illed bowel loops and contrast-enhanced vessels. Various types of neutral oral contrast used for small bowel imaging include water, water and methylcellulose, lactulose, polyethylene glycol, or a low-concentration (0.1% w/v) barium solution mixed with sorbitol (Fig. 50-85).659 Although water is inexpensive and well tolerated, it often is absorbed rapidly and provides suboptimal bowel distention, particularly in the distal small bowel.659,807 Methylcellulose has an unpleasant taste.215 Polyethylene glycol, despite its excellent bowel distention,455,458,537,807 is a cathartic, and the urge to evacuate can be great.215 The low-concentration (0.1% w/v) barium solution mixed with sorbitol is widely accepted; sorbitol minimizes small bowel absorption of water. The low concentration of barium produces approximately 20 HU, which is slightly higher than water attenuation. One study showed that this solution provided signiicantly better small bowel distention and visualization of mural features than water mixed with methylcellulose.567 The amount and timing of oral contrast for optimal distention of the entire small bowel is not yet standardized. Studies have used approximately 1 to 2 L administered in divided doses over time spans ranging from 30 minutes to 2 hours before the scan. Bowel distention for MRI examination can be achieved using methods similar to those for CT enterography. CT scan for enterography should be performed using a thin-slice thickness to allow high-quality coronal or sagittal images as well as 3D reconstruction. With the current scanners already in widespread use

FIG 50-84 Normal coronal CT enterography image after oral administration of Gastrograin as a positive oral contrast.

FIG 50-85 Normal coronal CT enterography image after oral administration of water as a neutral oral contrast.

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PART II CT and MR Imaging of the Whole Body

(i.e., 16- or 64-detector MDCT), 1-mm slice thickness or less is easily obtained without motion artifact. IV contrast injection at a rate of 3 mL/sec or greater is recommended to obtain good bowel wall enhancement. Optimal scan delay depends on the indications. In most cases, particularly in the evaluation of Crohn’s disease and bowel obstruction, single-phase imaging with a scan delay of approximately 45 to 50 seconds, the so-called enteric phase wherein bowel wall enhancement is maximized, is most appropriate.659,771 In cases of suspicious GI bleeding or ischemia, multiphasic scans are necessary. In cases of suspicious GI bleeding, a nonenhanced scan may also be helpful in the detection of high-attenuating acute hematoma.

MRI MRI has the advantage of not using ionizing radiation and has better soft tissue contrast compared to CT, although it has inferior spatial and temporal resolution compared with CT. Appropriate sequences for small bowel examination are yet to be standardized. In general, both transverse and coronal images using fast T2-weighted sequences, such as half-Fourier acquisition single-shot turbo-spin echo (HASTE) technique and true-FISP, and using fast gradient echo T1-weighted sequences with and without IV contrast are often obtained. The appropriate scan delay for a contrast-enhanced study is yet to be determined. In contrast to CT, where the enteric phase is approximately 45 to 50 seconds after contrast injection,659,771 bowel wall enhancement on MRI was shown to be maximal during the portal phase (at 70 seconds).462 Given that MRI does not have a radiation hazard, multiple image acquisitions from 45 seconds into the portal phase may be a good strategy to image optimal bowel enhancement (Fig. 50-86).215

CT and MR Angiography CT angiography (CTA) and MR angiography (MRA) are highly effective methods for evaluating mesenteric vasculature and have replaced most conventional catheter-based diagnostic angiography techniques (Fig. 50-87). For high-quality imaging of mesenteric vessels using CT and MRI, careful attention to technical factors such as amount of IV contrast, injection rate, scan timing, slice collimation, reconstruction thickness, and reconstruction increment is required.

FIG 50-86 Normal coronal T2-weighted HASTE MR enterography image after oral administration of polyethylene glycol as a contrast agent.

Amount of IV Contrast and Injection Rate. Regarding the amount of IV contrast, both ixed amount336,334 and body weight–adjusted amount (e.g., 2 mL/kg body weight for CTA)352 can be used. The body weight–adjusted method is based on the fact that the magnitude of vascular and parenchymal contrast enhancement of a given amount of contrast is inversely related to the body weight. With both methods, 120 to 150 mL of IV contrast agent is typically used for abdominal CTA of an adult patient. In terms of injection rate, higher rate is favored for two reasons. First, the magnitude of peak aortic enhancement increases with increase of injection rate.28 Second, faster injection rate shortens the time to peak arterial enhancement such that a greater temporal separation between the arterial and venous phases is obtained.28 For abdominal CTA, contrast injection at 3 to 5 mL/sec via 18- or 20-gauge angiocatheter in the antecubital fossa is typically used.

Scan Timing. In terms of scan timing, ixed scan delay336,334 and customized scan delay using test-bolus28,352 or bolus-tracking28 methods can be used. Fixed scan delay is simpler to use. However, it does not relect individual variations in circulation time and may result in suboptimal contrast enhancement in some patients. Customized scan delay considers the fact that optimal scan delay depends on several factors: (1) contrast medium injection duration, (2) contrast arrival time (Tarr), and (3) scan duration.27,28 Tarr varies among individuals according to their cardiac output and can be measured by using testbolus28,352 or bolus-tracking28 methods. The test-bolus method measures aortic attenuation by using a region of interest (ROI) placed over the lower portion of the descending thoracic aorta or the upper portion of the abdominal aorta after administration of a small amount of contrast agent as a test bolus (e.g., 15-20 mL for CTA). Then Tarr is deined as the time to maximal enhancement of the aorta after injection of a test bolus. Some have used Tarr measured with the test-bolus method as the scan start time for arterial-phase CTA103,352,755,789 or MRA,815 whereas others have added additional time delay to Tarr to calculate optimal scan start time, because the former method may result in earlier-than-optimal imaging acquisition.27,28 In the bolus-tracking method, the regular amount of contrast needed for angiographic examination is given to the patient, and ROI measurement of aortic attenuation is performed in a manner similar to that for the test-bolus method. In the case of CTA, Tarr is obtained by measuring the time needed for aortic attenuation to reach 50 to 100 HU above baseline attenuation after contrast injection.28 With the contrast arrival time (obtained as above) and injection duration, the time to peak aortic enhancement can be estimated as follows: injection duration + (0-10 seconds)29 and injection duration + (Tarr − 15) + (0-10 seconds)28 for CTA, and Tarr + injection duration/2187,478,691,692 for MRA. Optimal scan delay (i.e., optimal scan start time) for arterial-phase angiography can be calculated by subtracting half of the scan duration from the time to peak aortic enhancement so that peak aortic enhancement falls right in the middle of the scan duration or coincides with the center of k-space data acquisition.27,28 Optimal scan delay for arterial-phase angiography is therefore: injection duration + (0-10 seconds) − scan duration/229 and injection duration + (Tarr − 15) + (0-10 seconds) − scan duration/228 for CTA, and Tarr + injection duration/2 − scan duration/2187,478,691,692 for MRA. In contrast to the complexity of scan timing for arterial-phase angiographic examination, scan timing for the mesenteric or portal venous system is relatively straightforward. For most cases, a 60- to 70-second delay after contrast injection would be appropriate.28,336

Slice Collimation, Reconstruction Thickness, and Reconstruction Increment. Slice collimation should be the thinnest possible to

CHAPTER 50

Gastrointestinal Tract

A

B

C FIG 50-87 Dynamic vascular phases on normal CT mesenteric angiography. A, Arterial phase (coronal MIP image). B, Portal phase (coronal MIP image). C, Coronal volume-rendering image.

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cover the entire scan range in a single breath hold in order to visualize ine details of mesenteric vessels: typically 0.75 mm on a 16-detector MDCT and 0.6 mm on a 64-detector MDCT. Overlapping image reconstruction should always be performed to improve 3D postprocessing.487 A reconstruction increment of 50% to 75% of the reconstruction thickness (e.g., 0.5- to 0.75-mm increment or 0.25- to 0.5-mm overlap with 1-mm reconstruction thickness) is generally appropriate.487 In addition to the traditional transverse images, coronal and sagittal images are very useful for evaluation of mesenteric vessels. Sagittal projection is particularly useful when evaluating the origin and proximal portions of the mesenteric arteries. Both volume-rendering and MIP are widely used postprocessing techniques for vascular evaluation. The smallest vascular branches are often best appreciated with MIP technique.

PATHOLOGIC CONDITIONS Benign Neoplasms Although the small intestine represents about 75% of the total length of the GI tract and more than 90% of its total mucosal surface, it is the site of fewer than 25% of all GI neoplasms and fewer than 2% of all malignant neoplasms.924 Five neoplasms making up 95% of benign small bowel tumors include benign stromal tumors, lipomas, adenomas, ibromas, and hemangiomas.151 Lipomas are slow-growing tumors composed of well-differentiated adipose tissue surrounded by a ibrous capsule. They are usually solitary, but small bowel lipomatosis has been reported.632 Some 90% to 95% of lipomas are submucosal and tend to prolapse into the bowel lumen. Lesions larger than 2 cm in diameter produce abdominal pain, diarrhea, constipation, or blood loss when the overlying mucosa is ulcerated or intestinal obstruction develops secondary to intussusception.833 On CT the diagnosis can be easily made by the tumor’s characteristic fatty CT attenuation (Fig. 50-88). MRI is also useful in diagnosis because lipomas appear hyperintense on T1-weighted images. Focal areas of soft tissue attenuation may be occasionally seen on CT in a lipomatous mass, especially in cases with intussusception. This inding may be caused by focal ischemic change and does not indicate liposarcoma. Multiple hemangiomas have been reported to involve the bowel and represent an important diagnostic consideration in patients with hemangiomatosis of the lower extremity. Phleboliths are frequently detected within hemangiomatous masses, providing a clue to their nature.605

A

Apart from these ive benign neoplasms, inlammatory ibroid polyps can develop in the small intestine, especially at the ileum in 70% of cases (Fig. 50-89). They originate primarily in the submucosa and are composed of ibroblasts, blood vessels, and inlammatory cells within an edematous and collagenous stroma. Most lesions are solitary and large, often causing bowel obstruction due to intussusception. No distinctive radiologic features have been noted between these tumors and other mural or intraluminal lesions.

Malignant Neoplasms The most common histologic types of malignant tumors include adenocarcinoma, carcinoid tumor, lymphoma, and malignant stromal tumor. The nonspeciic nature of symptoms contributes to the delayed diagnosis of small intestinal tumors, generally resulting in the poor prognosis of these patients. Even though barium studies such as enteroclysis and small bowel follow-through examinations have been used as primary diagnostic methods, CT and MRI not only have become primary tools in patients with a palpable mass, small bowel

M

FIG 50-89 Enterocolic intussusception due to inlammatory ibroid tumor of the ileum. CT scan shows a heterogeneous mass in the rightsided colon, with interposed mesenteric fat (arrowhead) and vessels (arrow). A round mass (M) is seen at the lead point.

B FIG 50-88 Multiple lipomas in the small intestine. A and B, CT scan shows multiple lipomas (arrow) in the small bowel loops.

CHAPTER 50 obstruction, or known lymphoma but also play a large role in preoperative staging and follow-up. The detection rate of the small bowel neoplasm was 80% in a series using single-detector CT,463 and 84.7% in another recent series that used CT enteroclysis.684 Dudiak and colleagues were able to suggest a speciic tumor diagnosis in 60% of patients with adenocarcinomas, 58% of patients with lymphomas, and 33% of those with carcinoid tumors and malignant stromal tumors.184 CT is helpful in staging small bowel malignancy, but reported accuracy was not high (47%) in a series that included 15 patients with small bowel adenocarcinoma.97

Adenocarcinoma. Primary adenocarcinoma of the small intestine is rare, accounting for approximately 40% of malignant tumors of the

Gastrointestinal Tract

small intestine. When this lesion occurs, it generally arises in the proximal jejunum. Risk factors for development of small bowel adenocarcinoma include a history of Crohn’s disease, sprue, Peutz-Jeghers syndrome, Lynch syndrome II, congenital bowel duplication, ileostomy, or duodenal or jejunal bypass surgery. The most frequent gross types are iniltrative, resulting in early bowel obstruction, and ulcerative, as represented by bleeding. Polypoid forms are uncommon. Adenocarcinomas tend to metastasize early to regional lymph nodes and invade the mesenteric vessels when they are located near the mesenteric root. On CT scans, the tumor appears as an eccentric focal mass or a circumferential bowel wall thickening in a short segment (Figs. 50-90 and 50-91). Narrowing of the lumen and dilatation of the proximal bowel are also common. However, tumors smaller than 2 cm

A

B FIG 50-90 Primary ileal adenocarcinoma. Axial (A) and coronal (B) CT scans show circumferential thickening (arrowheads) of the ileum, without obstruction.

A

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B FIG 50-91 Primary jejunal adenocarcinoma. A, Coronal true-FISP MRI shows a high-signal-intensity mass (arrowheads) obstructing the small bowel loop. B, Gd-enhanced MRI shows a high-signal-intensity mass (arrows) at the site of bowel obstruction.

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in diameter may be missed by CT and are better detected by barium study.463

Carcinoid Tumor. After the appendix, the small bowel is the second most frequent site of carcinoid tumors, representing up to 20% of GI carcinoids; 90% of these tumors are located in the ileum. Carcinoid tumors vary in appearance from a small submucosal lesion to a large intraluminal ulcerating lesion. The tumor tends to iniltrate the mesentery, causing characteristic desmoplastic mesenteric reactions such as angulation, kinking, rigidity, and separation of small bowel loops. Despite widespread metastases, the primary tumor itself may be dificult to detect on CT or even at laparotomy, owing to its small size. Therefore some researchers advocate the use of scintigraphy using meta-iodobenzylguanidine labeled with iodine-131 as a screening procedure in patients thought to have carcinoid tumors.6 The carcinoid syndrome, which includes diarrhea, lushing, and abdominal pain, occurs in 2% of cases of small bowel carcinoid, but it is much more likely to be present in cases of hepatic metastasis.820 CT may show virtually pathognomonic features, with a mesenteric mass associated with radiating linear or curvilinear soft tissue strands (Figs. 50-92 and 50-93). Calciications are seen in approximately 70% of cases with mesenteric carcinoid tumor.644 The occurrence of retroperitoneal lymphadenopathy is not rare.683 Small bowel obstruction may develop as a result of desmoplastic reaction or serosal disease. CT features of small bowel carcinoid tumor may be similar in appearance to those of lymphoma, metastasis, Crohn’s disease, and mesothelioma. 18 FDG has not demonstrated signiicant uptake in well-differentiated neuroendocrine tumors such as carcinoid tumor and is only indicated in cases with less-differentiated tumors without somatostatin receptors and with high proliferative activity.79 For this reason, 18FDG positivity can be used as a prognostic parameter of aggressiveness.

Gastrointestinal Stromal Tumor. GISTs are the most common mesenchymal malignancy of the GI tract despite the fact that they account for only approximately 1% to 3% of all malignant GI tumors.252 Speciic immunohistochemical properties of GISTs for KIT (CD117, a tyrosine kinase growth factor receptor) have allowed GISTs to be distinguished from other mesenchymal tumors of the GI tract such as leiomyomas, leiomyosarcomas, schwannomas, and neuroibromas.583,765 Up to 94% of patients with GISTs express CD117 (KIT protein) and thus share similar markers with the interstitial cells

of Cajal.581 Mutations in the KIT oncogene of GIST resulted in constitutive activation of KIT receptor tyrosine kinase in GISTs. Thus KIT is not only the principal marker for diagnostic purposes but also a speciic target for systemic therapy.324 Stromal tumors are usually solitary benign tumors that are categorized by their differentiation into smooth muscle or neural tissue. Tumors are classiied as benign, borderline, or malignant. In contrast to benign stromal tumors (leiomyomas) that occur anywhere in the small intestine, malignant stromal tumors (leiomyosarcomas) arise more commonly in the ileum than in the jejunum. Symptoms depend on the growth pattern—submucosal, subserosal, or intraluminal. On CT and MRI, this tumor appears as a large heterogeneous mass with areas of low attenuation from hemorrhage, necrosis, or cyst formation502 and often grows in an exoenteric pattern with a large extraluminal component (Fig. 50-94). Severe hemorrhage within the mass, which is associated with hypervascular stromal tumors, produces a luid-luid level. Calciication is occasionally demonstrated.133 Even in the presence of large tumor, the incidence of bowel obstruction is rare. Some large cavitary tumors may show aneurysmal dilatation of the lumen, which is regarded as a fairly speciic inding of lymphoma.764 Lymphadenopathy is not a common inding. Differentiation between benign and malignant stromal tumors is radiologically dificult, but CT indings favoring malignant stromal tumor include a mass larger than 5 cm, lobulated contour, heterogeneity with central necrosis or liquefaction, mesenteric iniltration, regional lymphadenopathy, and exophytic growth.133 Metastasis occurs by direct extension and the hematogenous route. However, intraperitoneal spread (peritoneal leiomyosarcomatosis) may occur by intraperitoneal seeding via ascitic luid or by embolic metastases or rupture of the primary tumor,580,729 and it is more commonly seen in signiicantly larger or exophytically growing tumors.729 The most common CT manifestations of peritoneal tumor seeding include multiple well-deined peritoneal nodules or masses with or without a smudged or granular pattern of omental iniltration (Fig. 50-95).729 Lymphadenopathy is rare, and ascites may be seen but usually in small amount.863 These CT indings may simulate those of peritoneal carcinomatosis from GI or ovarian malignancies.729 However, multiple discrete peritoneal nodules are uncommon in

C

FIG 50-93 Mesenteric changes in a carcinoid tumor. Stellate, centripFIG 50-92 Carcinoid tumor. CT scan shows an intramural mass (C) in the bowel loop near the ileocecal region. Visualization of the primary carcinoid tumor is unusual. (From Megibow AJ, Balthazar EJ: CT of the gastrointestinal tract. St. Louis, 1986, CV Mosby.)

etally oriented, thickened mesenteric vessels are seen subtending a dilated “kinked” loop of distal ileum (arrows). The primary tumor is not visualized. (From Megibow AJ, Balthazar EJ: CT of the gastrointestinal tract. St. Louis, 1986, CV Mosby.)

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B

A

FIG 50-94 Malignant GIST of the ileum. An ileal mass (arrows) with a lobulated surface can be seen on oblique coronal T2-weighted HASTE (A) and axial T2-weighted FISP (B) MRI. High signal intensity within the mass indicates tumoral necrosis.

*

*

*

FIG 50-95 Peritoneal tumor seeding in malignant GIST of the ileum. Axial CT scan shows multiple heterogeneously enhancing masses (asterisks) in the omentum and mesentery.

peritoneal carcinomatosis.290 Therefore CT features of peritoneal tumor seeding from GIST are more likely close to those of peritoneal tumor spread from hepatocellular carcinoma411 or other benign condition of leiomyomatosis peritonealis disseminata.648 Imatinib mesylate, a selective inhibitor of constitutive activity of KIT receptor tyrosine kinase in the cells of GIST, was introduced as a chemotherapeutic agent in the late 1990s and is now becoming promising for the management of patients with advanced GIST. In general, CT is regarded as the modality of choice in monitoring tumor response. The current gold standard for evaluating the response to imatinib treatment is monitoring the changes of tumor size on CT. However, use of tumor size criteria by measuring only the longest dimension is sometimes unreliable and may underestimate tumor response. Use of

the combination indings of tumor size, tumor attenuation, and the presence or absence of tumor nodules and vessels therefore seems reasonable.128,786 After chemotherapy with imatinib mesylate, in addition to size reduction, CT attenuation values become changed from hyperattenuating into hypoattenuating patterns (Fig. 50-96). Therefore liver metastasis responding to imatinib treatment appears to be cystic, sometimes mimicking simple hepatic cyst. In some tumors the size becomes paradoxically enlarged or tumor attenuation is increased despite signiicant clinical improvement, mostly owing to the development of intratumoral hemorrhage. In our experience in 21 patients in whom CT and pathologic correlation was possible, the histopathologic indings of the tumors contributing to the changes of tumor attenuation included hemorrhagic necrosis, cystic change, myxoid degeneration, hyalinization, or calciication. On FDG PET, metastasizing lesions show increased FDG uptake, and nonmetastasizing lesions do not show signiicant FDG uptake.318 In a study by Goerres and colleagues, who compared CT and CT PET in patients with GISTs after treatment with imatinib mesylate, CT detected more lesions than on PET, and FDG uptake was sometimes quite variable. However, CT PET gave more prognostic information than CT did; patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity.259

Lymphoma. Types of lymphoma that may involve the small bowel include T-cell lymphoma, B-cell lymphoma, low-grade B-cell lymphoma (lymphoma of mucosa-associated lymphoid tissue [MALT]), Mediterranean lymphoma (immunoproliferative small intestinal disease), follicular lymphoma, Burkitt’s lymphoma, mantle cell lymphoma, and Hodgkin’s disease.747 Lymphoma accounts for approximately 20% of all small bowel tumors. The small intestine closely follows the stomach as the most frequent site of disease, and multicentric involvement occurs in 10% to 25% of cases.503 Almost all small bowel lymphomas are non-Hodgkin’s lymphoma; most of them are of

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PART II CT and MR Imaging of the Whole Body

FIG 50-97 Lymphoma. Axial CT scan shows concentric bowel wall

A

thickening (arrows) in the ileum. Note enlarged lymph node (arrowhead) along the ileocolic vessels.

M

B FIG 50-96 Ileal malignant GIST after imatinib mesylate therapy. A, Axial CT scan shows a large heterogeneous enhancing ileal mass (arrowheads) with lobulated contour. B, CT obtained 12 months after starting chemotherapy shows marked shrinkage of tumor, with decreased CT attenuation value (arrows).

B-cell origin, but the cases complicating celiac disease are of T-cell origin. Predisposing conditions include AIDS, celiac disease, systemic lupus erythematosus (SLE), Crohn’s disease, and a history of chemotherapy.81 In children and young adults, lymphoma primarily affects the ileocecal region; in adults the distal ileum is the most frequent site of tumor.503 In lymphoma complicating celiac disease, however, the proximal jejunum is usually involved. Although the CT appearance of lymphomas is variable, these tumors can be classiied as follows754: 1. Circumferential or iniltrative forms are characterized by concentric bowel wall thickening (Fig. 50-97). Aneurysmal dilatation of the lumen, regarded as one of the most characteristic features of lymphoma, occurs in approximately 50% of cases.184,463 Except for cases with developing intussusception, bowel obstruction is rare because the tumor weakens the muscularis propria of the bowel wall and does not elicit a desmoplastic response.754 2. Cavitary or endoexenteric forms are the second most commonly occurring pattern (Fig. 50-98). Cavitation of the tumor bulk results from ulceration of the mucosa with extension to the intramural portion of the tumor. Compared with stromal or epithelial tumors, the lymphomatous mass characteristically shows poorer contrast enhancement. Perforation of the tumor

A

n M n

B FIG 50-98 Non-Hodgkin’s lymphoma of the jejunum—diffuse large B-cell type. A, CT shows a large cavitary mass (M) in the jejunum, with diffuse mesenteric lymphadenopathy (not shown). B, FDG PET scan clearly shows areas with abnormal FDG uptake corresponding to the lesions seen on CT scans. M, mass; n, nodes.

may occur secondary to a lack of desmoplastic response to tumor growth, as a result of rapid tumor growth, or as a response to therapy308 (Fig. 50-99). Fistulization to the skin, solid organs, or bladder develops in 5% to 15% of cases.96 3. Mesenteric forms are usually manifested as diffuse lymphadenopathy in the mesentery as well as in the retroperitoneum. A

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Gastrointestinal Tract

1657

n n

FIG 50-100 Non-Hodgkin’s lymphoma of the mesentery—diffuse large FIG 50-99 Perforated small bowel lymphoma after chemotherapy. On CT scan the bowel wall involved with lymphoma is focally perforated (arrow) along with evidence of a large amount of ascites and diffuse omental iniltration.

“sandwich” appearance is demonstrated when mesenteric masses surround mesenteric vessels but leave intact a thin rim of preserved perivascular fat (Fig. 50-100). The small bowel loops are displaced, focally invaded, or occasionally obstructed by mesenteric masses. Mesenteric lymphoma may also appear as an ill-deined conluent mass enguling and encasing multiple loops of adjacent bowel or as a conglomerate mantle of mesenteric tissue. 4. Polypoid forms appear as single or multiple polypoid masses in the small intestine (Fig. 50-101). The incidence of intussusception is very high. Therefore differentiation of this form of lymphoma from intestinal polyposis syndrome may sometimes be dificult. However, the presence of lymphadenopathy in the mesentery or other sites may give the clue for establishing the diagnosis. 5. Nodular forms consist of submucosal nodules that are widely distributed in the small intestine. If these nodules do not reach a suficient size, CT may not be helpful in their detection. The prevalence of lymphomas has been reported to be increased in patients with AIDS or in posttransplantation patients. In nearly all cases the pathologic type is non-Hodgkin’s lymphoma. The CT appearance of lymphoma in these immunocompromised hosts is indistinguishable from that of lymphoma in nonimmunocompromised patients. MRI appears comparable to CT in demonstrating the morphologic changes in the GI tract as well as in the peritoneal cavity in patients with small bowel lymphomas. Contrast-enhanced MRI had an advantage in depicting the submucosal tumor location by demonstrating a three-zone appearance: (1) a high-intensity mucosa, (2) an intermediate-intensity submucosal tumor iniltration, and (3) a lowintensity proper muscular layer.131 FDG PET has become a well-accepted method for diagnosis, staging, evaluating treatment response, and follow-up of patients with malignant lymphoma (see Figs. 50-98B and 50-101B). In addition, as the degree of FDG uptake is related to tumor grade, PET scanning can be used to estimate tumor grade prior to histologic classiication.744 Although the use of only FDG PET may create dificulty in differentiating the high-grade non-Hodgkin’s lymphoma from other neoplastic or inlammatory disease, interpreting the results of a careful clinical

B-cell type. CT scan shows conglomerate lymphadenopathy (n) in the mesentery, surrounding mesenteric vessels with intact perivascular fat.

history, the extent of the disease, and corresponding CT images can contribute to the correct diagnosis. After treatment, evaluation of treatment response is an important aspect in the management of lymphomas. However, in the presence of residual mass, CT is often unable to discriminate between vital tumor and inactive ibrotic tissue. FDG PET is reported to be superior to CT in predicting the residual tumor or relapse after treatment, with higher speciicity and positive predictive value than those of CT.452 In monitoring patients with high-grade non-Hodgkin’s lymphoma of the GI tract, the standard uptake value (SUV) plays a role; the SUV measurement is signiicantly decreased after therapy.674 Persistent FDG uptake after therapy may help predict treatment failure or a high risk of recurrence. False-positive scans can be caused by a variety of pathologic processes such as sarcoidosis, TB, histoplasmosis and other fungal infections, pyogenic abscess, spondylodiscitis, any process that results in an iniltration of metabolically active host cells,745 and inlammatory changes after treatment. Apparent accumulation of FDG PET in the GI tract may be a false-positive inding resulting from a combination of normal peristaltic activity, GI lymphoid tissue, and excreted radiotracer within the bowel lumen. False-negative scans can be seen in patients with minimal residual disease after treatment or in patients with malignant lymphoma that is not highly metabolically active. Thus low-grade lymphoma may be overlooked,373 and MALT lymphoma can be the cause of false-negative scan.326 Peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is a rare disease in Western countries, affecting middle-aged patients; it represents lymphoma bearing a mature T-cell phenotype and excluding mycosis fungoides and cutaneous T-cell lymphoma.3 PTCL accounts for 5% to 30% of all non-Hodgkin’s lymphomas.4 Although the most common sites of extranodal involvement include bone marrow, skin, lung, and liver, the GI tract is rarely affected (