The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications: Update 2018

This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications : Update 2018

Funding Information: Odd Helge Gilja: Advisory Board/Consultant fee from: AbbVie, Bracco, GE Healthcare, Samsung, and Takeda Paul S. Sidhu: Speaker honoraria, Bracco, Siemens, Samsung, Hiatchi, GE and Philips 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 Vito Cantisani: Speaker honoraria, Canon/Toshiba, Bracco, Samsung Dominique Amy: Speaker honoraria, Hitachi, Supersonic, EpiSonica Marco Brock: Speaker honoraria, Hitachi Fabrizio Calliada: Speaker honoraria, Bracco, Hitachi, Shenshen Mindray Dirk Andre Clevert: Speaker honoraria, Siemens, Samsung, GE, Bracco, Philips; Advisory Board, Siemens, Samsung, Bracco, Philips Jean-Michel Correas: Speaker honoraria, Hitachi-Aloka, Canon/Toshiba, Philips, Supersonic, Bracco, Guerbet; Research collaboration, Bracco Sonocap, Guerbet NsSafe and Secure protocols Mirko D’Onofrio: Speaker honoraria, Siemens, Bracco, Hitachi; Advisory Board Siemens, Bracco Andre Farrokh: Speaker honoraria, Hitachi Pietro Fusaroli: Speaker honoraria, Olympus Roald Flesland Havre: Speaker honoraria, GE Healthcare, Conference participation support from Pharmacosmos, Ultrasound equipment from Samsung Medison André Ignee: Speaker honoraria: Siemens, Canon/Toshiba, Hitachi, Boston Scientific, Bracco, Supersonic, Abbvie Christian Jenssen: Speaker honoraria, Bracco, Hitachi, Canon/Toshiba, Falk Foundation, Covidien; Research grant, Novartis Maija Radzina: Speaker honoraria, Bracco, Canon/Toshiba Luca Sconfienza: Travel grants from Bracco Imaging Italia Srl, Esaote SPA, Abiogen SPA, Fidia Middle East. Speaker honoraria from Fidia Middle East Ioan Sporea: Speaker honoraria, Philips, GE, Canon/Toshiba; Advisory Board Member, Siemens; Congress participation support, Siemens Mickael Tanter: Speaker honoraria, Supersonic; Co Founder and shareholder, Supersonic; Research collaboration, Supersonic Peter Vilmann: Speaker honoraria, Pentax, Norgine; Advisory Board, Boston Scientific; Consultancy MediGlobe The following members declared no conflicts of interest: Adrian Săftoiu, Michael Bachmann Nielsen, Flaviu Bob, Jörg Bojunga, Caroline Ewertsen, Michael Hocke, Andrea Klauser, Christian Kollmann, Kumar V Ramnarine, Carolina Solomon, Daniela Fodor, Horia Ștefănescu Publisher Copyright: © 2019 Georg Thieme Verlag KG Stuttgart New York.This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography.Peer reviewe

Ultrasound shear wave imaging for diagnosis of nonalcoholic fatty liver disease

Pour le diagnostic et la stratification de la fibrose hépatique, la rigidité du foie est un biomarqueur quantitatif estimé par des méthodes d'élastographie. L'élastographie par ondes de cisaillement (« shear wave », SW) utilise des ultrasons médicaux non invasifs pour évaluer les propriétés mécaniques du foie sur la base des propriétés de propagation des ondes de cisaillement. La vitesse des ondes de cisaillement (« shear wave speed », SWS) et l'atténuation des ondes de cisaillement (« shear wave attenuation », SWA) peuvent fournir une estimation de la viscoélasticité des tissus. Les tissus biologiques sont intrinsèquement viscoélastiques et un modèle mathématique complexe est généralement nécessaire pour calculer la viscoélasticité en imagerie SW. Le calcul précis de l'atténuation est essentiel, en particulier pour une estimation précise du module de perte et de la viscosité. Des études récentes ont tenté d'augmenter la précision de l'estimation du SWA, mais elles présentent encore certaines limites. Comme premier objectif de cette thèse, une méthode de décalage de fréquence revisitée a été développée pour améliorer les estimations fournies par la méthode originale de décalage en fréquence [Bernard et al 2017]. Dans la nouvelle méthode, l'hypothèse d'un paramètre de forme décrivant les caractéristiques spectrales des ondes de cisaillement, et assumé initialement constant pour tous les emplacements latéraux, a été abandonnée permettant un meilleur ajustement de la fonction gamma du spectre d'amplitude. En second lieu, un algorithme de consensus d'échantillons aléatoires adaptatifs (« adaptive random sample consensus », A-RANSAC) a été mis en œuvre pour estimer la pente du paramètre de taux variable de la distribution gamma afin d’améliorer la précision de la méthode. Pour valider ces changements algorithmiques, la méthode proposée a été comparée à trois méthodes récentes permettant d’estimer également l’atténuation des ondes de cisaillements (méthodes de décalage en fréquence, de décalage en fréquence en deux points et une méthode ayant comme acronyme anglophone AMUSE) à l'aide de données de simulations ou fantômes numériques. Également, des fantômes de gels homogènes in vitro et des données in vivo acquises sur le foie de canards ont été traités. Comme deuxième objectif, cette thèse porte également sur le diagnostic précoce de la stéatose hépatique non alcoolique (NAFLD) qui est nécessaire pour prévenir sa progression et réduire la mortalité globale. À cet effet, la méthode de décalage en fréquence revisitée a été testée sur des foies humains in vivo. La performance diagnostique de la nouvelle méthode a été étudiée sur des foies humains sains et atteints de la maladie du foie gras non alcoolique. Pour minimiser les sources de variabilité, une méthode d'analyse automatisée faisant la moyenne des mesures prises sous plusieurs angles a été mise au point. Les résultats de cette méthode ont été comparés à la fraction de graisse à densité de protons obtenue de l'imagerie par résonance magnétique (« magnetic resonance imaging proton density fat fraction », MRI-PDFF) et à la biopsie du foie. En outre, l’imagerie SWA a été utilisée pour classer la stéatose et des seuils de décision ont été établis pour la dichotomisation des différents grades de stéatose. Finalement, le dernier objectif de la thèse consiste en une étude de reproductibilité de six paramètres basés sur la technologie SW (vitesse, atténuation, dispersion, module de Young, viscosité et module de cisaillement). Cette étude a été réalisée chez des volontaires sains et des patients atteints de NAFLD à partir de données acquises lors de deux visites distinctes. En conclusion, une méthode robuste de calcul du SWA du foie a été développée et validée pour fournir une méthode de diagnostic de la NAFLD.For diagnosis and staging of liver fibrosis, liver stiffness is a quantitative biomarker estimated by elastography methods. Ultrasound shear wave (SW) elastography utilizes noninvasive medical ultrasound to assess the mechanical properties of the liver based on the monitoring of the SW propagation. SW speed (SWS) and SW attenuation (SWA) can provide an estimation of tissue viscoelasticity. Biological tissues are inherently viscoelastic in nature and a complex mathematical model is usually required to compute viscoelasticity in SW imaging. Accurate computation of attenuation is critical, especially for accurate loss modulus and viscosity estimation. Recent studies have made attempts to increase the precision of SWA estimation, but they still face some limitations. As a first objective of this thesis, a revisited frequency-shift method was developed to improve the estimates provided by the original implementation of the frequency-shift method [Bernard et al 2017]. In the new method, the assumption of a constant shape parameter of the gamma function describing the SW magnitude spectrum has been dropped for all lateral locations, allowing a better gamma fitting. Secondly, an adaptive random sample consensus algorithm (A-RANSAC) was implemented to estimate the slope of the varying rate parameter of the gamma distribution to improve the accuracy of the method. For the validation of these algorithmic changes, the proposed method was compared with three recent methods proposed to estimate SWA (frequency-shift, two-point frequency-shift and AMUSE methods) using simulation data or numerical phantoms. In addition, in vitro homogenous gel phantoms and in vivo animal (duck) liver data were processed. As a second objective, this thesis also aimed at improving the early diagnosis of nonalcoholic fatty liver disease (NAFLD), which is necessary to prevent its progression and decrease the overall mortality. For this purpose, the revisited frequency-shift method was tested on in vivo human livers. The new method's diagnosis performance was investigated with healthy and NAFLD human livers. To minimize sources of variability, an automated analysis method averaging measurements from several angles has been developed. The results of this method were compared to the magnetic resonance imaging proton density fat fraction (MRI-PDFF) and to liver biopsy. SWA imaging was used for grading steatosis and cut-off decision thresholds were established for dichotomization of different steatosis grades. As a third objective, this thesis is proposing a reproducibility study of six SW-based parameters (speed, attenuation, dispersion, Young’s modulus, viscosity and shear modulus). The assessment was performed in healthy volunteers and NAFLD patients using data acquired at two separate visits. In conclusion, a robust method for computing the liver’s SWA was developed and validated to provide a diagnostic method for NAFLD

Viscoelasticity Imaging of Biological Tissues and Single Cells Using Shear Wave Propagation

Changes in biomechanical properties of biological soft tissues are often associated with physiological dysfunctions. Since biological soft tissues are hydrated, viscoelasticity is likely suitable to represent its solid-like behavior using elasticity and fluid-like behavior using viscosity. Shear wave elastography is a non-invasive imaging technology invented for clinical applications that has shown promise to characterize various tissue viscoelasticity. It is based on measuring and analyzing velocities and attenuations of propagated shear waves. In this review, principles and technical developments of shear wave elastography for viscoelasticity characterization from organ to cellular levels are presented, and different imaging modalities used to track shear wave propagation are described. At a macroscopic scale, techniques for inducing shear waves using an external mechanical vibration, an acoustic radiation pressure or a Lorentz force are reviewed along with imaging approaches proposed to track shear wave propagation, namely ultrasound, magnetic resonance, optical, and photoacoustic means. Then, approaches for theoretical modeling and tracking of shear waves are detailed. Following it, some examples of applications to characterize the viscoelasticity of various organs are given. At a microscopic scale, a novel cellular shear wave elastography method using an external vibration and optical microscopy is illustrated. Finally, current limitations and future directions in shear wave elastography are presented

Viscoelasticidad renal durante la disminución gradual de flujo sanguíneo en un modelo porcino in vivo: estudio piloto

Elasticity imaging methods have been used to study kidney mechanical properties and have demonstrated that the kidney elastic modulus increases with disease state. However, studies in swine suggest that kidney elastic modulus is also affected by hemodynamic variables. A newly emerging method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) offers a tool to determine renal elasticity and viscosity in vivo. The purpose of this study was directed toward evaluating the feasibility of SDUV for in vivo measurements of healthy swine kidney during acute gradual decease of renal blood flow. In this study in vivo SDUV measurements were made on a group of 5 normal swine kidneys at baseline renal blood flow (RBF) and 25, 50, 75 and 100% decrease in RBF. The shear elastic modulus at full baseline was 7.04 ± 0.92 kPa and 3.48 ± 0.20 kPa at 100% decrease in RBF. The viscosity did not change between baseline (2.23 ± 0.33 Pa•s) and 100% decrease in RBF (2.03 ± 0.32 Pa•s). The data from this study indicates that other variables such as local blood flow, pressure and volume as well as method accuracy need to be measured to illustrate the relationship between shear elasticity and viscosity associated with acute kidney processes.Métodos de imágenes de elasticidad se han utilizado para estudiar las propiedades mecánicas renales y han demostrado que el módulo elástico de los riñones del aumenta con el estado de enfermedades renales. Sin embargo, estudios en cerdos sugieren que el riñón módulo elástico también se ve afectada por las variables hemodinámicas. Un método emergente llamado Shearwave Dispersion Ultrasound Vibrometry (SDUV) ofrece una herramienta para determinar la elasticidad y la viscosidad renal. El propósito de este estudio se dirige a la evaluación de la viabilidad de SDUV para mediciones las propiedades viscoelasticas del riñón saludable durante variación aguda del flujo sanguíneo renal. En este estudio el método SDUV se realizó en un grupo de 5 riñones porcinos normales al inicio del flujo sanguíneo renal (RBF) basal y 25, 50, 75 y 100% de disminución en el RBF. El módulo elástico basal fue de 7,04 ± 0,92 kPa y 3,48 ± 0,20 kPa a 100% de disminución del RBF. La viscosidad no cambió entre el momento basal (2,23 ± 0,33 Pa • s) y el 100% de disminución del RBF (2,03 ± 0,32 Pa • s). Los datos de este estudio indican que variables tales como el flujo local de sangre, la presión y el volumen así como el método exactitud deben ser medidos para ilustrar la relación entre la elasticidad y la viscosidad asociada con los procesos renales agudos

Elastografia epatica: metodiche a confronto

Background: The cirrhotic process of liver injury is the end-stage of hepatic fibrosis, which results from progressive accumulation of extracellular matrix during the wound-healing response of the liver to repeated injury. Mortality and morbidity rates increase exponentially once cirrhosis develops. Therefore, a prompt assessment of the degree of severity of fibrosis, an accurate and timely diagnosis of liver cirrhosis and management of complications are important in guiding therapy management in chronic liver disease. Liver biopsy is often required, but it is an invasive procedure, with a risk of severe complications (1/4000–10,000). In addition, its accuracy is prone to sampling error (6) and inter-and/or intra-observer diagnostic discrepancies occur in up to 10–20% of liver biopsies. For this reason, there is increasing interest in non-invasive methods for detecting liver fibrosis. Ultrasound-based transient elastography (TE) is one of the first non-invasive imaging methods to be used in common practice. The technique is based on low-frequency vibrations: shear waves produced by the ultrasound machine propagate through the tissue and produce an elastic deformation, with the premise that liver stiffness (LS) measurements reflect the degree of hepatic fibrosis. Displacement is reflected in the variation of the acquired echo signals. The Siemens-based ARFI system and Philips Elast PQTM use conventional US to generate a shear wave directly within the liver tissues. This allows the sonographer to obtain both conventional US images and also specify a region of interest (ROI) for estimation of liver stiffness. The propagation velocity of the shear wave is reported in metres per second, and correlates with liver stiffness. The direct generation of shear wave within the liver tissue holds advantages over TE since it is not subject to chest/abdominal wall distortion of the waves. Results: 110 consecutive patients with liver disease underwent a liver biopsy and liver stiffness assessment by Philips EPIQ 7TM ultrasound system, Siemens Acuson (ARFI) ultrasound system, 2 and Echosens FibroscanTM (currently the best-validated technique). The results of these three imaging techniques were compared with histological results. A direct, strong correlation was observed between LS values assessed by TE elastography by Elast PQ and Virtual Touch (p < 0.0001) and Metavir score

Validation of liver elastography in patients with primary sclerosing cholangitis and healthy individuals. Normal values and correlation to fibrosis parameters.

Liver elastography applies ultrasound-based measurements of liver stiffness (LS), used as a quantification of liver fibrosis. Correlation between liver stiffness measurements (LSM) and histological stages of liver fibrosis was already established; however, technological and methodological differences between ultrasound equipment and biological differences related to age or liver disease etiology, may influence the interpretation of LSM. Correct assessment of disease relies on a precise definition of normality, but reference values and inter-system differences were lacking for several elastography systems. Data were particularly scarce for children and patients with primary sclerosing cholangitis (PSC). In this rare and complicated liver disease, non-invasive surveillance of fibrosis development is recommended as part of follow-up. Thus, we aimed to establish reference values for LSM in children and adults using several elastography systems and to compare principally different methods such as transient elastography (TE), point shear wave elastography (pSWE), and two-dimensional shear wave elastography (2D-SWE) in a head-to-head setup. We furthermore investigated, for the first time, the feasibility of pSWE and 2D-SWE in PSC patients. In studies II and III, we included 343 healthy individuals aged 4-70 years. Applying two or three elastography systems head-to-head in every participant, we defined age-specific reference values for each system. Reference values were determined for different age groups: 4-7 years, 8-11 years, 12–14 years, 15–17 years, and 20–70 years. We found a gender difference in subjects 12–70 years, with no similar difference in young children. LSM was higher in adolescents and adults compared to younger children. Correlation between different observers was good. In studies I and IV, a cohort of adult PSC patients was followed, collecting clinical data and performing LSM and blood tests. Paper I describes pSWE in PSC for the first time, comparing assessments of both liver lobes and concluding that left liver LSM is unreliable; hence, subsequent measurements forming Paper IV were applied in the right liver lobe only. All PSC patients were examined by pSWE at every visit. For Paper IV, all patients were examined head-to-head by both pSWE, 2D-SWE, and TE: all three systems were feasible in PSC patients, and all were highly correlated with other indications of liver fibrosis (B-mode findings, liver biochemistry, fibrosis scores, and prognostic scores). In conclusion, the results demonstrate that elastography systems representing three principally different methods are feasible and perform well in healthy subjects and PSC patients. We have established reference values for healthy children and adults, with head-to-head inter-system comparisons and descriptions of interobserver differences. Ultrasound elastography of the liver should be adopted broadly in the medical environment; in screening, diagnostics, and clinical patient follow-up of both children and adults.Doktorgradsavhandlin

Liver Biopsy

Liver biopsy is recommended as the gold standard method to determine diagnosis, fibrosis staging, prognosis and therapeutic indications in patients with chronic liver disease. However, liver biopsy is an invasive procedure with a risk of complications which can be serious. This book provides the management of the complications in liver biopsy. Additionally, this book provides also the references for the new technology of liver biopsy including the non-invasive elastography, imaging methods and blood panels which could be the alternatives to liver biopsy. The non-invasive methods, especially the elastography, which is the new procedure in hot topics, which were frequently reported in these years. In this book, the professionals of elastography show the mechanism, availability and how to use this technology in a clinical field of elastography. The comprehension of elastography could be a great help for better dealing and for understanding of liver biopsy

Early identification of kidney allograft dysfunction with in vivo viscoelastic response (VisR) ultrasound

Ten percent of American adults, more than 20 million people, have chronic kidney disease (CKD). The symptoms of CKD start silently, progress through renal dysfunction, and terminate in end-stage renal disease. The most desirable and cost-effective treatment for CKD is renal transplantation. Although transplant surgery techniques and postoperative care have greatly advanced, ten‐year graft survival is 59%, and death‐censored graft survival is 74%. Improving long-term graft survival is one of the major unmet needs in kidney transplantation. Current graft assessment methods include noninvasive, surrogate biomarkers like serum creatinine and proteinuria. However, these biomarkers lack sensitivity and specificity. In the absence of reliable surrogate biomarkers, some transplant programs implement surveillance or ‘protocol’ biopsies. However, biopsies are associated with bleeding complications and, in rare cases, transplant loss. A noninvasive, sensitive, and specific measure of renal allograft dysfunction is needed to enable timely intervention and prolong graft life. The goal of this dissertation is to develop Viscoelastic Response (VisR) ultrasound for noninvasively characterizing the viscoelastic and anisotropic properties of the kidney to delineate early features associated with renal allograft failure. Such features will include those associated with parenchymal fibrosis and inflammation, which are sensitive and specific indications of early allograft dysfunction. Particularly, this dissertation seeks to improve VisR estimation of tissue elasticity, viscosity, and mechanical anisotropy in isotropic and transversely isotropic viscoelastic materials. Association of VisR metrics with renal fibrosis and inflammation in vivo in the swine model is demonstrated. Additionally, this work evaluates VisR metrics relative to kidney allograft status in a cross-sectional pilot clinical study. Finally, it presents the intra-observer reproducibility of VisR parameters and variability in VisR outcomes due to the donor type, sex, race, and BMI of renal transplant patients. Overall, this dissertation represents a large step toward noninvasive and early identification of graft dysfunction.Doctor of Philosoph