Dedicated to Albrecht, who is no longer with us

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1 Dedicated to Albrecht, who is no longer with us

2 Springer-Verlag Italia SrI.

3 L. Solbiati A. Martegani E. Leen J.M. Correas P.N. Burns D. Becker Contrast-Enhanced Ultrasound of Liver Diseases With contributions by L. Aiani A. Bauer' A. Bellobuono C. Borghi L. Cova O. HeIenon V. Kirn V. Osti M. Tonolini 'springer

Dr. LUIGI SOLBIATI Chairman, Dr. ALBERTo MARTEGANI Servizio di Radiologia Ospedale Valduce Via Dante 11 1-22100 Como, Italy Dr.

4 Dr. LUIGI SOLBIATI Chairman, Dr. ALBERTo MARTEGANI Servizio di Radiologia Ospedale Valduce Via Dante Como, Italy Dr. EDWARD LEEN Consultant Radiologist/Senior Lecturer University of Glasgow Royal Infirmary Alexandra Parade Glasgow G31 2ER, UK Dr. JEAN MICHEL CORREAS Service de Radiologie Adulte Hopital Necker Enfants Malades 149 rue de Sevres Paris Cedex 15, France Dr. PETER N. BURNS Depts. of Medical Biophysics and Radiology University of Toronto Sunnybrook and Women's Health Sciences Centre Toronto, Canada Dr. DIRK BECKER Chairman, Dept. of Medicine Gastroenterology, Intensive Care Medicine Eckernf6rde Community Hospital Schleswiger Str D Eckernf6rde, Germany Contributors L. Aiani A. Bauert A. Bellobuono C. Borghi L. Cova O. Helenon V. Kirn V. Osti M. Tonolini Springer-Verlag Italia 2003 Originally published by Springer-Verlag Italia, Milano in 2003 Softcover reprint of the hardcover 1st edition 2003 ISBN ISBN (ebook) DOI / Library of Congress Cataloging-in-Publication Data: applied for This work is subject to copyright. AlI rights are reserved, whether the whole or part of the material is concerned, specificaliy the rights of translation, reprinting, re-use of illustrations, re citation, broadcasting, reproduction on mîcrofilms or in other ways, and storage in databanks. Duplication of this publication or parts thereof is only permitted under the provisions of the Italian Copyright Law in its current version and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the Italian Copyright Law. The use of general descriptive names, registered names, trademarks, etc., in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. This textbook was funded in part by an educational grant from Bracco. Bracco, however, exercises no editorial comment, review, or any other type of control over the content of this texthook. For any product or type of product, whether a drug or devîce, referenced in this texthook, physicians should carefuliy review the product's package insert, instructions for use, or user manual prior to patient administration to ensure proper utilization of the product. Typesetting: Compostudio, Cernusco sul Naviglio (Milano) Cover design: Simona Colomho (Milano) SPIN:

5 Preface In the last few years, the development of sonographic contrast agents - or "microbubbles" - has stimulated increasingly intensive studies on the relationships between ultrasound and contrast media. As a result, "contrast -specific" hardware and software systems have been introduced by different ultrasound manufacturers with impressive speed. This has finally led to the birth of a very new imaging modality - "contrast-enhanced sonography" (CEUS). Since 1999, the introduction of second-generation contrast agents has represented a decisive step towards the extensive clinical use of CEUS and has simultaneously made obsolete most, if not all, scientific publications available so far. This book is, to our knowledge, the first to deal entirely with secondgeneration contrast agents and the most updated contrast-specific software for noncardiologic uses. The reasons why the liver has been chosen as the only "target" of the book are easily understandable by radiologists and hepatologists alike. The study of vascularity is the only purpose of CEUS, and the liver has a unique vascular system, with two different inflow systems resulting in a single outflow. Furthermore, the pathologically different focal liver lesions (FLLs) are mostly characterized by different "models" of vascularity: CEUS can mimic contrastenhanced computed tomography and magnetic resonance imaging, basing differential diagnosis on the morphological and temporal characteristics of enhancement, but with the additional unique advantage of the study being done in real-time. Technological aspects of contrast agents and related sonographic hardware and software are described in the first chapters of the book. In the clinical sections, the outstanding concepts of liver physiology (mostly vascular) are reviewed and the vascular patterns of various types of FLLs are described, in correlation with histopathology and clinical data. The implications derived from the addition of CEUS to other imaging modalities currently employed are discussed chapter by chapter and completed with considerations on the diagnostic work-up of each type of FLL. In the "hands-on" section, with extremely practical suggestions, an explanation is given on how this new imaging modality can be used to fulfill the needs of radiologists, hepatologists, and oncologists. Being a new modality, it is also important to be aware of the major pitfalls of CEUS and to "adapt" its technique to different clinical situations, with knowledge of various tips and tricks: all this is summarized in the final chapters.

6 VI Preface This text is the result of the collaboration of a group of "pioneers" of CEUS who, continuously exchanging new ideas and experiences, have also progressively increased their friendly relationships. Unfortunately, the very first pioneer of the group, our great friend Albrecht, is no longer with us: we will always miss his valuable professional contributions and, more importantly, his friendship.

7 Contents 1 Contrast Ultrasound Technology 1 P.N. BURNS 1. 1 Introduction: The Need for Bubble-Specific Imaging Bubble Behaviour and Incident Pressure The Mechanical Index (MI) Nonlinear Backscatter: Harmonic Imaging Harmonic B-Mode Imaging Harmonc Doppler Harmonic Power Doppler Imaging Tissue Harmonic Imaging Pulse Inversion Imaging Power Pulse Inversion Imaging Transient Disruption: Intermittent Imaging Triggered Imaging Intermittent Harmonic Power Doppler for Perfusion Imaging Summary Safety Considerations Conclusion 18 References 18 2 Ultrasound Contrast Agents 21 A. BAUER t, L. SOLBIATI 2.1 Introduction Basic Physics and Pharmacology Commercial Ultrasound Contrast Media Albunex ptison Levovist Sono Vue DefinityTM Imagent Future Developments in Ultrasound Contrast Media 25 References 25

8 VIII Contents 3 Liver Physiology 27 D. BECKER 3.1 Introduction Anatomy Liver Lobule Structure Liver Cell Plate Nonparenchymal Liver Cells Sinusoidal Endothelial Cells Kupffer Cells Hepatic Stellate Cells Fibrosis and Hepatic Stellate Cells Pit Cells Hepatocyte Transport Electrolyte and Solute Transport Bile Formation Functional Organization of the Liver Cell Plate Limiting Plate Hepatocyte Heterogeneity Along the Liver Cell Plate Carbohydrate Metabolism Fatty Acid Metabolism Amino Acid and Ammonia Metabolism Regulation of Hepatocyte Heterogenicity Physiologic Significance of Hepatocyte Heterogenicity 35 References 36 4 Macro- and Microcirculation of Focal Liver Lesions Traumatic Abdominal Lesions 37 A. MARTEGANI, 1. AIANI Introduction Ultrasound and Abdominal Trauma Contrast-Enhanced Ultrasound Image Gallery Conclusions 43 References Hepatic Hemangiomas 44 A. MARTEGANI, C. BORGHI Anatomical and Structural Features Diagnostic Imaging Integrated Imaging Contrast-Enhanced Ultrasound Imaging Differential Diagnostic Problems 48 References Hepatic Adenoma SOLBIATI, M. TONOLINI, A. BELLOBUONO References 55

9 Contents IX 4.4 Macro- and Microcirculation of Focal Nodular Hyperplasia 56 E. LEEN References Other Benign Lesions and Pseudolesions SOLBIATI, V. KIRN, 1. COVA Inflammatory Pseudotumor of the Liver Hepatic Tuberculoma Focal Fatty Changes Skip Areas in Diffuse Steatosis 61 References Hepatocellular Carcinoma and Dysplastic Lesions SOLBIATI, M. TONOLINI, 1. COVA Introduction and Epidemiology Pathology and Hepatocarcinogenesis Unenhanced Sonography Contrast-Enhanced Ultrasound 68 References Liver Metastases 79 A. MARTEGANI, 1. AIANI Anatomical and Structural Features Diagnostic Imaging Integrated Imaging Contrast-Enhanced Ultrasound Imaging Differential Diagnostic Problems 87 References Other Malignancies 89 M. TONOLINI, 1. COVA, V. OSTI, 1. SOLBIATI Peripheral Cholangiocarcinoma Hepatic Sarcoma Hepatic Lymphoma 92 References 93 5 Medical Needs 95 E. LEEN 5.1 Introduction Incidental Lesions in Normal Livers Screening and Surveillance for Hepatocellular Carcinoma Staging and Follow-up of Cancer Patients 98 References 100

10 X Contents 6 Guidance and Control of Percutaneous Treatments 1. SOLBIATI, M. TONOLINI, 1. COVA 6.1 Introduction 6.2 Fundamentals and Pathology of Ablative Treatments 6.3 Role of Diagnostic Imaging 6.4 Detection of Lesions and Selection of Patients 6.5 RF Procedures and Targeting of Lesions 6.6 Assessment of Therapeutic Response References 7 Hands-on Contrast Ultrasound J.M. CORREAS, O. HELENON 7. 1 Tips and Tricks Organization of Contrast-Enhanced US Intravenous Access Preparation of the USCA The USCAs Scanning Techniques and Settings Liver CEUS using Levovist Liver CEUS using SonoVue 7.2 Limitations 7.3 Artifacts and Pitfalls Heterogeneous Enhancement

11 Contributors LUCAAIANI Servizio di Radiologia Ospedale Valduce Via Dante Como, Italy ALBRECHT BAUER t Bracco Diagnostics Inc. Princeton, NJ, USA DIRK BECKER Chairman, Dept. of Medicine Gastroenterology, Intensive Care Medicine Eckernforde Community Hospital Schleswiger Str D Eckernforde, Germany ANDREA BELLO BUONO CLAUDIA BORGHI Servizio di Radiologia Ospedale Valduce Via Dante Como, Italy PETER N. BURNS Depts. of Medical Biophysics and Radiology University of Toronto Sunnybrook and Women's Health Sciences Centre Toronto, Canada JEAN MICHEL CORREAS Service de Radiologie Adulte H6pital Necker Enfants Malades 149 rue de Sevres Paris Cedex 15, France LUCA COVA O. HELENON Service de Radiologie Adulte H6pital Necker Enfants Malades 149 rue de Sevres Paris Cedex 15, France VALENTINA KIRN EDWARD LEEN Consultant Radiologist/Senior Lecturer University of Glasgow Royal Infirmary Alexandra Parade Glasgow G31 2ER, UK ALBERTO MARTEGANI Servizio di Radiologia Ospedale Valduce Via Dante Como, Italy

12 XII Contributors VALERIA OSTI MASSIMO TONOLINI LUIGI SOLBIATI Chairman,

Enhancing the Role of Ultrasound with Contrast Agents

Enhancing the Role of Ultrasound with Contrast Agents Riccardo Lencioni (Ed.) Enhancing the Role of Ultrasound with Contrast Agents 123 EDITOR Prof. Dr. Riccardo Lencioni Division of Diagnostic and Interventional