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Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US., Competing Interests: All other authors have received lecture honoraria from Bracco and from companies selling ultrasound systems. Martin Krix is employee of Bracco., (Thieme. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: Fabio Piscaglia declares the following COI: Esaote, Bracco, Bayer, Samsung (lecturing or consultant or advisory board honoraria). All other authors have no COI to declare.

Competing Interests: Vito Cantisani declares SIUMB, SIRM, ESR, EFSUMB and WFUMB membership and lectured for Bracco, Samsung, Canon.Fabio Piscaglia declares SIUMB, EFSUMB and WFUMB membership, member of the Governing Board of the International Contrast Ultrasound Society and collaborations with Esaote (research contract and speaker bureau honoraria), Bayer (speaker bureau and advisory board), Bracco (speaker bureau), Samsung (speaker bureau), Astrazeneca (advisory board), EISAI (speaker bureau and advisory board), MSD (speaker bureau and advisory board), IPSEN (speaker bureau), Tiziana Life Sciences (advisory board) and Roche (advisory board).Christian Jenssen declares DEGUM, EFSUMB and WFUMB membership and lectured for GE.Christoph Frank Dietrich declares EFSUMB and WFUMB membership.Caroline Ewertsen declares EFSUMB and WFUMB membership.

Competing Interests: COI for companies related to imaging. Honoraria for: Speaker bureau from Bayer, ESAOTE, Samsung; Consultancy: GE, Bracco. Advisory Board travel support: Siemens Healthineers.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients., Competing Interests: Christoph F Dietrich: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Pentax, Olympus, Fuji, Boston Scientific, AbbVie, Falk Foundation, Novartis, Roche; Advisory Board Member, Hitachi, Mindray, Siemens; Research grant, GE, Mindray, SuperSonic Richard G Barr: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Philips, Siemens, Lantheus, Canon; Advisory Board – Lanteus and Bracco Diagnostics; Board Member – ICUS; Research Grants – Siemens Ultrasound, Philips Ultrasound, GE Ultrasound, GE Medical, Mindray, SuperSonic Imagine, B and K Ultrasound Annalisa Berzigotti: Research grant, Bracco Byung Ihn Choi: Speaker honoraria, Samsung Dirk André Clevert: Speaker honoraria, Bracco, GE, Samsung, Philips, Siemens, Falk Foundation Jean-Michel Correas: Speaker Honoraria, Canon MS, Hitachi MS, Philips US, SuperSonic Imagine, Novartis, Johnson & Johnson; Speaker honoraria, Bracco SA: Principal investigator of BR1-127 et SonoCap studies; Speaker honoraria, Guerbet SA: Principal investigator of NsSafe and Secure studies Odd Helge Gilja: Speaker honoraria, GE Healthcare, Takeda AS; Advisory Consulting, GE, Takeda and Samsung Vito Cantisani: Speaker honoraria, Samsung, Bracco, Canon J. Brian Fowlkes: Research grants, Philips Healthcare, GE Healthcare; Stock Ownership, Histosonics Adrian Lim: Advisory Board, Canon Medical Systems, Carestream; Research grant – Philips Medical Systems; Speaker honoraria – Canon, Bracco Maria Franca Meloni: Speaker honoraria, Bracco Christian Jenssen: Speaker honoraia, Hitachi, Bracco, Falk Foundation; Expert witness, Hitachi Mirko D’Onofrio: Speaker honoraria, Bracco, Siemens; Advisory Board, Bracco, Siemens, Hitachi; Research grant, Hitach; Congress Support, Bracco, Siemens Fabio Piscaglia: Speaker honoraria, Bracco, Bayer, EISAI, Guerbet; Advisory board honoraria: Bayer, EISAI; Research Contract: ESAOTE Masatoshi Kudo: Speaker honoraria, Bayer, Eisai, MSD, Ajinomoto; Research Grants, Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai, Bayer, Abbvie, Medico’s Hirata, Astellas Pharma, Bristol-Myers Squibb; Advisory Consulting, Kowa, MSD, BMS, Bayer, Chugai, Taiho, Eisai, Ono pharmaceutical Yi Dong: Speaker honoraria, Bracco, Siemens Yuko Kono: Equipment support Canon, GE; Contast agent support Lantheus, Bracco Andrej Lyshchik: Speaker honoraria, GE Healthcare, Siemens, Canon; Advisory Board, Bracco Diagnostics; Consulting, GE Healthcare; Speaker panel, GE Healthcare, SonoScape; Royalties, Elsevier Zheng Rongqin: Speaker honoraria, Bracco, Esaote; Research grant, Philips; Congress support, Bracco Paul Sidhu: Speaker honoraria, Bracco, Siemens, Hitachi, GE healthcare, Philips, Samsung, Advisory Board ITREAS Ltd The following have declared no conflict of interest: Peter Burns, Cristina Chammas, Nitin G Chaubal, Pintong Huang, Andre Ignee, Nathalie Lassau, Jae-Young Lee, Yasunori Minami, Carlos Nicolau, Christian Nolsoe, Xin-Wu Cui, Adrian Saftoiu, Guido Torzilli, Ping Liang, Fuminori Moriyasu, Xiaoyan Xie, (Thieme. All rights reserved.)

Competing Interests: Fabio Piscaglia: Esaote: Research Contract with the Department. Personal honoraria for speaker bureau/advisory board/consultancies from: Alkermes, Astrazeneca, Bayer, Bracco, BMS, La Force Guerbet, EISAI, GE, IPSEN, MDS Roche Tiziana Life Siemens Healthcare: support for accommodation at advisory board.Vito Cantisani lectured for Bracco, Samsung, Canon.

Competing Interests: Fabio Piscaglia: Bayer, ESAOTE, La Force Guerbet, GE Healthcare, Bracco, Siemens Healthineers; Federico Stefanini: None; Vito Cantisani: Bracco, Samsung, Canon; Paul Sidhu: Bracco, Siemens Healtineers, Samsung, Hitachi, GE Healthcare, Philips, ITREAS; Richard Barr: Philips, Mindray, Siemens, Canon, Bracco, Hologic, Samsung; Annalisa Berzigotti: none; Maria Cristina Chammas: none; Jean-Michel Correas: Canon MS, Hitachi MS, Philips Ultrasound, Siemens Ultrasound, Supersonic Imagine; Christopher Frank Dietrich: Bracco, Hitachi, Pentax, Siemens Healthcare, Mindray, Supersonic, Jazz, Youkey; Steven Feintstein: Bracco, DIA-Imaging, GE Healthcare; Pintong Huang: Bracco, Philips, Mindray; Christan Jenssen: FALK Foundation, Hitachi, Canon, Bracco and GE; Yuko Kono: Bracco, Lantheus, GE, Canon; Masatoshi Kudo: Bayer, Eisai, GE Healthcare; Ping Liang: None; Andrej Lyshchik: GE Healthcare, Bracco Diagnostics, Siemens Healthineers, Canon Medical Systems, Elsevier; Christian Nolsoe: None; Xyaoyan Xie: None; Francesco Tovoli: Bayer

Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications., Competing Interests: Fabrizio Calliada: Congress participation support, Toshiba, Guerbet, Bayer, Hitachi, MindrayVito Cantisani: Congress participation support, Toshiba, Guerbet, Bayer, Hitachi, MindrayDirk Clevert: Speaker honoraria for Siemens, Philips, Samsung Falk, Bracco; Advisory Board Member Siemens, Philips, Samsung, Bracco; Research grants, Siemens, Philips, Samsung, BraccoDavid Cosgrove: Speaker honoraria, Bracco, Toshiba, SuperSonic, BK Medical, Carestream; Advisory Board Member, Toshiba, Carestream; Research grant, Carestream; Congress participation support, Bracco, ToshibaAnnamarie Dagenello: Speaker honoraria, BraccoChristoph F Dietrich: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Pentax, Olympus, Fuji, Covidien, Boston Scientific, AbbVie, MSD, Falk Foundation, Novartis, Roche; Advisory Board Member, Hitachi and Mindray; Research grant, Bracco, Hitachi, GE, Siemens, Mindray, SuperSonic; Congress participation support, IPSENOdd Helge Gilja: Speaker honoraria, GE Healthcare Takeda AS and Meda ASChristian Jenssen: Speaker honoraria, Bracco, Hitachi, Toshiba, Falk Foundation, Covidien; Research grant, NovartisNathalie Lassau: Speaker honoraria, Bracco, Toshiba; Congress participation support, Bracco, ToshibaEdward Leen: Research equipment support, Philips Healthcare & SuperSonic ImagingMaria Franca Meloni: Speaker honoraria, BraccoChristian Pállson Nolsøe: Speaker honoraria and congress participation support, GE Healthcare and NeovitalisMirko D’Onofrio: Speaker honoraria, Bracco, Siemens; Advisor Board Member, Bracco, Siemens, Congress participation support, BraccoFabio Piscaglia: Speaker honoraria Bracco, Bayer; Advisory Board Member, Bayer; Research support, EsaoteMaija Radzina: Speaker honoaria, Bayer, Covidien; Congress participation support, BayerAdrian Saftiou: Speaker honoraria, Pentax Medical Singapore Ltd; Consulting/Advisory board, Mediglobe Corporation Gmbh; Congress participation support, Hitachi Medical Systems UKPaul Sidhu: Speaker honoraria, Siemens, Bracco, Hitachi, Philips and GEHans-Peter Weskott: Speaker honoraria for Bracco, Samsung and GEThe following members declared no conflicts of interest: Eva Bartels, Michele Bertolotto, Francesca Drudi, Simon Freeman, Christopher Harvey, Ernst Michael Jung, Andrea Klauser, Carlos Nicolau, Francesco Prada, Luca Savelli, Hessel Wijkstra, (© Georg Thieme Verlag KG Stuttgart · New York.)

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications., Competing Interests: Fabrizio Calliada: Congress participation support, Toshiba, Guerbet, Bayer, Hitachi, MindrayVito Cantisani: Congress participation support, Toshiba, Guerbet, Bayer, Hitachi, MindrayDirk Clevert: Speaker honoraria for Siemens, Philips, Samsung Falk, Bracco; Advisory Board Member Siemens, Philips, Samsung, Bracco; Research grants, Siemens, Philips, Samsung, BraccoDavid Cosgrove: Speaker honoraria, Bracco, Toshiba, SuperSonic, BK Medical, Carestream; Advisory Board Member, Toshiba, Carestream; Research grant, Carestream; Congress participation support, Bracco, ToshibaAnnamarie Dagenello: Speaker honoraria, BraccoChristoph F Dietrich: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Pentax, Olympus, Fuji, Covidien, Boston Scientific, AbbVie, MSD, Falk Foundation, Novartis, Roche; Advisory Board Member, Hitachi and Mindray; Research grant, Bracco, Hitachi, GE, Siemens, Mindray, SuperSonic; Congress participation support, IPSENOdd Helge Gilja: Speaker honoraria, GE Healthcare Takeda AS and Meda ASChristian Jenssen: Speaker honoraria, Bracco, Hitachi, Toshiba, Falk Foundation, Covidien; Research grant, NovartisNathalie Lassau: Speaker honoraria, Bracco, Toshiba; Congress participation support, Bracco, ToshibaEdward Leen: Research equipment support, Philips Healthcare & SuperSonic ImagingMaria Franca Meloni: Speaker honoraria, BraccoChristian Pállson Nolsøe: Speaker honoraria and congress participation support, GE Healthcare and NeovitalisMirko D’Onofrio: Speaker honoraria, Bracco, Siemens; Advisor Board Member, Bracco, Siemens, Congress participation support, BraccoFabio Piscaglia: Speaker honoraria Bracco, Bayer; Advisory Board Member, Bayer; Research support, EsaoteMaija Radzina: Speaker honoaria, Bayer, Covidien; Congress participation support, BayerAdrian Saftiou: Speaker honoraria, Pentax Medical Singapore Ltd; Consulting/Advisory board, Mediglobe Corporation Gmbh; Congress participation support, Hitachi Medical Systems UKPaul Sidhu: Speaker honoraria, Siemens, Bracco, Hitachi, Philips and GEHans-Peter Weskott: Speaker honoraria for Bracco, Samsung and GEThe following members declared no conflicts of interest: Eva Bartels, Michele Bertolotto, Francesca Drudi, Simon Freeman, Christopher Harvey, Ernst Michael Jung, Andrea Klauser, Carlos Nicolau, Francesco Prada, Luca Savelli, Hessel Wijkstra, (© Georg Thieme Verlag KG Stuttgart · New York.)

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts. The second part provides clinical information about the practical use of elastography equipment and the interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users., Competing Interests: Conflict of interest: Some authors declare conflicts of interest, which are available from the publisher., (© Georg Thieme Verlag KG Stuttgart · New York.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users., Competing Interests: Conflict of interest: Some authors declare conflicts of interest, which are available from the publisher., (© Georg Thieme Verlag KG Stuttgart · New York.)

Competing Interests: Conflict of Interest: Fabio Piscaglia: Speaker fees: Bayer, Bracco; Advisory board: Bayer; Research contract: Esaote. / Stephanie R. Wilson: Research support: Siemens, Philips; Advisory role: Lantheus / Andrej Lyshchik: Industry grant and Research support: GE, Siemens, Toshiba; Advisory Board: BRACCO; Speaker Panel: SonoScape / David Cosgrove: Speaker and MAB: Bracco Spa, Toshiba, Bk Medical, Clearstream / Christoph F. Dietrich: Advisory board: Hitachi, Mindray; Speaker honorarium: Hitachi, Supersonic, Siemens, Mindray, GE, Bracco, Pentax / Juergen K. Willmann: Research grant: Siemens, GE, Philips, Bracco; Consulting fees: Bracco, Triple Ring Technologies; Advisory board: Lantheus, Bracco, SonoVol / Claude B. Sirlin: Industry grant support: Siemens, GE, Gerber; Consulting and service agreements: Bracco / Yuko Kono: Grant and research support: Toshiba, GE, Philips; Advisory board and speaker fees: Bayer, Wako

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The sixth part of the Guidelines on Interventional Ultrasound produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for ultrasound guidance and assistance in vascular interventions. Based on convincing data, real-time sonographic guidance for central venous access is strongly recommended as a key safety measure. Systematic analysis of scientific literature shows that in difficult situations and special circumstances US guidance may also improve the efficacy and safety of peripheral venous and arterial access and endovascular interventions. Moreover, the recommendations of this guideline endorse the use of ultrasound to detect complications of vascular access and US-guided interventional treatment of arterial pseudoaneurysms., (© Georg Thieme Verlag KG Stuttgart · New York.)

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we summarise EFSUMB policy statements on medical student education in ultrasound., (© Georg Thieme Verlag KG Stuttgart · New York.)

In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(®), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4 cm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8 cm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(®) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(®) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2 - 3 cm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1 - 2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(®), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(®) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i. e., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5 Hz and in larger regions; thus this technique is also termed real-time 2 D SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(®) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. · The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e. g. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2 - 3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. · Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. · Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan®, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. · Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED), (© Georg Thieme Verlag KG Stuttgart · New York.)

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound (INVUS) assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, and safe and effective performance of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (long version)., (© Georg Thieme Verlag KG Stuttgart · New York.)

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (short version; the long version is published online)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Sorafenib is the reference therapy for advanced hepatocellular carcinoma (HCC). There is no method for predicting in the early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography allows assessment of tissue elasticity, we investigated the role of this ultrasound-based technique in the early prediction of tumor response to sorafenib in a HCC mice model., Materials and Methods: HCC subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle (17 mice) or treatment with sorafenib (19 mice). Strain elastosonography (Esaote, Italy) of the tumor mass was performed at different time points (day 0, + 2 and + 14 from treatment start) until the mice were sacrificed (day + 14). At the same time points, the volume was calculated with ultrasonography., Results: Sorafenib-treated mice showed a smaller increase in tumor size on day + 14 in comparison to vehicle-treated mice (tumor volume increase + 175 % vs. + 382 %, p = 0.009). The median tumor elasticity increased in both groups on day + 2 (+ 5.65 % and + 3.86 %, respectively) and decreased on day + 14 (-3.86 % and -3.63 %, respectively). However, among Sorafenib-treated tumors, 13 mice with a growth percentage delta < 200 % (considered as good treatment response) showed an increase in elasticity on day + 2 (+ 8.9 %, range -12.6 - + 64) while the other 6 with a growth percentage delta > 300 % (considered as poor treatment response) showed a decrease in elasticity (-17 %, range -30.2 - + 15.3) (p = 0.044)., Conclusion: Elastosonography appears to be a promising noninvasive new technique for the early treatment prediction of HCC tumor response to sorafenib. Specifically, an early increase in tumor elasticity (corresponding to tumors becoming softer) is associated with a good response., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To assess the impact of different vascular patterns at contrast-enhanced ultrasound (CEUS) on the characterization of small liver nodules (10-30 mm) in cirrhosis and to determine whether primary nodules and recurrent nodules (after a previously treated hepatocellular carcinoma) display variations in enhancement pattern., Materials and Methods: A total of 135 cirrhotic patients were evaluated. A diagnosis of hepatocellular carcinoma (HCC) was established according to AASLD Guidelines, based on imaging (computed tomography and/or magnetic resonance) or liver biopsy. All patients underwent CEUS. Different CEUS patterns were evaluated in terms of diagnostic accuracy: HYPER-HYPO: Arterial hyperenhancement followed by washout (hypoechoic appearance compared with surrounding parenchyma) in late phase; HYPER-ISO: Arterial hyperenhancement followed by isoenhancement (isoechoic appearance) in late phase; ISO-ISO: Isoenhancement in all vascular phases., Results: A total of 155 consecutive primary (n = 90) or recurrent (n = 65) nodules were detected. HCC was diagnosed in 127 nodules (71 primary, 56 recurrent). A characteristic HYPER-HYPO CEUS pattern was revealed in 52/127 (40.9%) HCCs (31 primary, 21 recurrent) giving a positive predictive value (PPV) of 98% (97% primary, 100% recurrent) and an accuracy of 51% (54% primary, 46% recurrent). A HYPER-ISO pattern was noted in 46 HCCs (31 primary, 15 recurrent). Assuming this pattern to also be indicative of HCC, the PPV and accuracy were 94% (93% primary, 97% recurrent) and 77% (84% primary, 68% recurrent), respectively. An ISO-ISO pattern was present in 29 HCCs (9 primary, 20 recurrent) and 22 non-HCCs (14 primary, 8 recurrent)., Conclusion: These data confirm that the HYPER-HYPO pattern at CEUS is definitely diagnostic for HCC in cirrhosis and that the HYPER-ISO pattern has a similar PPV, indicating that this pattern is highly suspicious for HCC. The ISO-ISO pattern was found in > 50% of recurrent nodules and indicates a high risk of HCC., (© Georg Thieme Verlag KG Stuttgart · New York.)

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way., (© Georg Thieme Verlag KG Stuttgart · New York.)

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts., (© Georg Thieme Verlag KG Stuttgart · New York.)

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide., (© Georg Thieme Verlag KG Stuttgart · New York.)

Dynamic Contrast Enhanced Ultrasound (DCE-US) is an imaging technique that utilizes microbubble contrast agents in diagnostic ultrasound. The EFSUMB guidelines published in 2004, updated in 2008 and 2011 focused on the use of DCE-US, including essential technical requirements, training, investigational procedures and steps, guidance on image interpretation, established and recommended clinical indications and safety considerations. However the quantification of images acquired with ultrasound contrast agents (UCAs) is not discussed in the guidelines. The purpose of this EFSUMB document is to provide some recommendations and descriptions of the quantification of ultrasound images, technical requirements for analysis of time-intensity curves (TICs), methodology for data analysis, and interpretation of the results., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan)., Materials and Methods: A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators., Results: The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874)., Conclusion: VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The typical appearance of focal nodular hyperplasia (FNH) in radiological contrast techniques (helical CT or MRI) includes homogeneous enhancement in the arterial phase, but the exact timing for the best visualization of this pattern is unknown. The aim of the present study was to assess the ultrasound pattern of FNH with special attention to real-time contrast-enhanced ultrasonography (CEUS) appearance and specifically to the timing of perfusion patterns., Materials and Methods: 72 patients (60 females, 12 males) with a total of 90 FNH nodules with a diameter ranging from 8 to 100 mm (mean +/- SD, 40.6 +/- 21.5 mm) were examined continuously for at least 4 minutes using CnTI and CPS methods (ESAOTE, Genoa, Italy and Acuson-Siemens) after bolus injection of SonoVue (BRACCO, Milan, Italy)., Results: 87 of 90 nodules showed the typical coin-like hyperechogenicity in the arterial phase. The remaining three nodules were all in the same patient and were diagnosed as FNH after resection. Contrast started to appear within the lesions after a mean of 15.7 +/- 4.6 seconds (range 7 - 27 s) and reached peak signal intensity, with the greatest differentiation between the lesion and the surrounding parenchyma, at around 22.6 +/- 7.0 seconds (range 14 - 72 s). In the late phase, 65 lesions (72.2 %) became isoechoic (after a mean of 80.8 +/- 85.7 s, range 20 - 300 s), 22 (24.4 %) slightly hyperechoic and 3 (3.3 %) faintly hypoechoic., Conclusion: FNH shows a typical homogeneous hyperechoic pattern during the arterial phase in real-time CEUS which disappears slowly on average but occasionally even as soon as 20 seconds after contrast injection. If the first scans are taken later than 20 seconds after injection (which is still considered to be a full arterial phase), the ultrasound hyperechogenicity may be missed in some cases. Real-time study of these lesions is therefore strongly recommended to avoid possible false-negative results., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)