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Advances in Diagnostic Imaging The Value of Contrast-Enhanced Ultrasound for Liver Advances in Diagnostic Imaging The Value of Contrast-Enhanced Ultrasound for Liver Editor Luigi Bolondi 123 Editor LUIGI BOLONDI Division of Internal Medicine Department of Internal Medicine and Gastroenterology University of Bologna, Italy Authors RICCARDO LENCIONI CLOTILDE DELLA PINA LAURA CROCETTI DANIA CIONI Division of Diagnostic and Interventional Radiology Department of Oncology, Transplants, and Advanced Technologies in Medicine University of Pisa, Italy HANS PETER WESKOTT Department of Internal Medicine Klinikum Hannover, Germany JEAN-MICHEL CORREAS1 AHMED KHAIROUNE1 ANAIS VALLET-PICHARD2 STANISLAS POL2 OLIVIER HÉLÉNON1 Department of Adult Radiology1 and Department of Hepatology2 Necker University Hospital, Paris, France ISBN-10 88-470-0457-8 Springer Milan Berlin Heidelberg New York ISBN-13 978-88-470-0457-3 Springer Milan Berlin Heidelberg New York This work is subject to copyright. All rights are reserved, whether the whole of part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in databanks. Duplication of this pubblication 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. Violations are liable for prosecution under the Italian Copyright Law. Springer is a part of Springer Science+Business Media springer.com © Springer-Verlag Italia 2006 Printed in Italy 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 publishers 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 book gathers the papers presented during a Bracco Symposium held on the occasion of EASL 2005. Bracco, however, exercises no editorial comment, review, or any other type of control over the content of this book. For any product or type of product, whether a drug or device, referenced in this book, physicians should carefully review the product’s package insert, instructions for use, or user manual prior to patient administration to ensure proper utilization of the product. Cover design: Simona Colombo, Milan Typesetting: Graficando, Milan Printing and binding: Arti Grafiche Nidasio, Milan Introduction It is well-known that, in the past few decades, imaging techniques, and in particular ultrasonography, have led to great advances in clinical hepatology. In fact, the widespread use of these techniques resulted in the clinical discovery of hepatocellular carcinoma and other liver tumours. Hepatocellular carcinoma was practically unknown to the clinician before the advent of diagnostic ultrasound. Real-time ultrasonography remains the most frequently used imaging procedure for the primary diagnosis of mass liver lesions and for the survey of patients affected by chronic liver diseases and tumours of the gastrointestinal tract. In recent years, however, the imaging-based diagnosis of mass liver lesions has become increasingly complicated due to the number and morphological variability of lesions that modern imaging techniques are currently able to display. If the sensitivity in detection has greatly increased, characterization has remained difficult and represents a critical challenge for the clinician. In this perspective, the use of contrast agents with CT scan and MRI has represented a significant advance, allowing not only the depiction of different patterns of enhancement related to the different vascular supply of each lesion, but also to the detection of a higher number of lesions that become visible in different phases of vascular perfusion. Hepatocellular carcinoma (HCC) most often displays a typical early arterial enhancement and a late washout of vascular contrast agents. This pattern, when confirmed by two different techniques, has been recognised by a panel of experts of the European Association for the Study of the Liver (EASL) as a valid VI Introduction criterion for the noninvasive diagnosis of HCC [1]. It is worth noting that duplex Doppler techniques are able to display some vascular abnormalities that characterise mass liver lesions; however, they are unable to display different phases of perfusion and have a overall sensitivity far less than that of contrast-enhanced CT and MRI. The availability of blood-pool contrast agents for ultrasound (US) together with the development of US harmonic imaging has opened up new perspectives both for the immediate characterization of any mass lesion detected in the liver and for increasing the sensitivity of ultrasonography in the detection of liver metastases. The technique was initially based on digital processing of nonlinear backscattered signals produced by the breaking of first-generation microbubble contrast agents when insonated by high acoustic pressure [mechanical index (MI) = 0.8–1.2] US waves. Nevertheless, since these microbubbles are destroyed by the high pressure, a certain amount of time (depending on the blood perfusion velocity in the explored tissue) must elapse to allow refilling of the microvessels by the contrast agent. As a result, signals originating from microbubble destruction must be explored by an intermittent imaging modality. This method is technically complicated, affected by artefacts, and does not allow continuous dynamic evaluation of vascular perfusion. In addition, at high acoustic pressure, harmonic signals may be also produced by the surrounding tissue, thus limiting the contrast resolution of the image. More recently, contrast-specific software and technologies have been developed that facilitate the analysis of harmonic signals originating from the insonation of second-generation US contrast agents by using extremely low acoustic pressure (MI = 0.04–0.1) US waves. These second-generation contrast agents are based on the more stable perfluorocarbon-filled or sulfur-hexafluoride-filled microbubbles and have a strong nonlinear harmonic response when insonated with low acoustic pressure.A second-generation blood pool agent, BR1 (SonoVue; Bracco, Milan, Italy), consisting of phospholipid-stabilised shell microbubbles filled with sulfur hexafluoride gas, is licensed for use Introduction in abdominal and vascular imaging in most European countries. The safety and effectiveness of this agent have been proved in preliminary experimental and clinical investigations. New US technologies avoid microbubble destruction and allow continuous real-time imaging of the liver parenchyma and of liver tumours during vascular perfusion. For this reason, the technique is also referred to as “perfusional angiosonography”, in order to distinguish it from techniques using first-generation contrast agents and intermittent imaging. Several contrast-specific US modes operating at low acoustic pressure have been introduced in clinical practice. Taking into account the great impact of this new technology on clinical practice, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) organised, in January 2004, in Rotterdam, a consensus meeting of experts in order to develop guidelines for the use of US contrast agents in the diagnosis of liver diseases [2]. The resulting document represents an important starting point for clinical implementation of this new diagnostic procedure. The guidelines as well as further advances in the clinical application of contrast-enhanced harmonic US were presented by a group of the experts (JM Correas, R Lencioni and HP Weskott) from the Rotterdam meeting at the Bracco satellite symposium, held in Paris in April 2005 during the annual EASL congress, and are reported in this booklet. Finally, in June 2005 a panel of experts from EASL, the American Association for the Study of the Liver (AASLD), and the Japanese Society of Hepatology (JSH) met at the EASL monothematic conference in Barcelona. This group reviewed both the data available in the literature and the body of clinical experience that has resulted from different eastern and western countries. The panel introduced contrast-enhanced harmonic US among the techniques able to provide specific findings for the diagnosis of HCC. The implementation of these guidelines will result in a considerable increase in the request for contrast-enhanced US procedures. Consequently, US services will have to update their equipment, provide proper training to physicians performing US ex- VII VIII Introduction aminations, and take into account the cost of introduction of these procedures into daily practice.Whether the eventual cost saving associated with reduced demand for CT or MR imaging of the liver after contrast-enhanced US largely counterbalances the cost of the examination should be investigated by a pharmaco-economical analysis. Luigi Bolondi Division of Internal Medicine Department of Internal Medicine and Gastroenterology University of Bologna, Italy ■ References 1. Bruix J, Sherman M, Llovet JM et al (2001) EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35: 421-430 2. Albrecht T, Blomley M, Bolondi L et al; EFSUMB Study Group (2004) Guidelines for the use of contrast agents in ultrasound. Ultraschall Med 25:249-256 Contents Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V LUIGI BOLONDI Chapter 1 Impact of European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on the Use of Contrast Agents in Liver Ultrasound . . . 1 RICCARDO LENCIONI, CLOTILDE DELLA PINA, LAURA CROCETTI, DANIA CIONI Chapter 2 The Role of Contrast-Enhanced Ultrasound (CEUS) in Identifying and Characterizing Focal Liver Lesions . . . . . . . . . . 15 HANS PETER WESKOTT Chapter 3 Contrast-Enhanced Ultrasound in the Management of Cirrhotic Patients: HCC Diagnosis,Staging and Monitoring of Percutaneous Treatments . . . . . . . . . . . . . . . . 47 JEAN-MICHEL CORREAS, AHMED KHAIROUNE, ANAIS VALLET-PICHARD, STANISLAS POL, OLIVIER HÉLÉNON RICCARDO LENCIONI, CLOTILDE DELLA PINA, LAURA CROCETTI, DANIA CIONI Chapter 1 Impact of European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on the Use of Contrast Agents in Liver Ultrasound RICCARDO LENCIONI, CLOTILDE DELLA PINA, LAURA CROCETTI, DANIA CIONI Division of Diagnostic and Interventional Radiology Department of Oncology, Transplants, and Advanced Technologies in Medicine University of Pisa, Italy ■ Introduction The detection and characterization of focal liver lesions is an important and challenging issue. Hepatocellular carcinoma (HCC) is the fifth most common cancer [1]. The liver is the organ most frequently involved by metastases from other tumors. In addition, benign liver lesions, such as hemangioma and focal nodular hyperplasia (FNH), have a high prevalence in the general population. Several imaging modalities and diagnostic protocols have been used in attempts to optimize detection and characterization of focal liver lesions. Ultrasound (US) is the most commonly used liver imaging modality worldwide. Unfortunately, it has limited sensitivity in the detection of small tumor nodules. Moreover, US findings are often nonspecific, as there are enough variability and overlap in the appearances of benign and malignant liver lesions to make a definite distinction problematic. Computed tomography (CT) and magnetic resonance (MR) imaging are commonly used to clarify questionable US findings and to provide a more comprehensive assessment of the liver parenchyma.