ARFI: from basic principles to clinical applications in diffuse chronic disease-a review

The many factors influencing the shear wave velocity (SWV) measured with Acoustic Radiation Force Impulse (ARFI) are examined in order to define the most correct examination technique. In particular, attention is given to the information achieved by experimental models, such as phantoms and animal studies. This review targets the clinical applications of ARFI in the evaluation of chronic diffuse disease, especially of liver and kidneys. The contribution of ARFI to the clinical workout of these patients and some possible perspectives are described

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

Ultrasound Elastography

Elastography, the science of creating noninvasive images of mechanical characteristics of tissues, has been rapidly evolving in recent years. The advantage of this technique resides in the ability to rapidly detect and quantify the changes in the stiffness of soft tissues resulting from specific pathological or physiological processes. Ultrasound elastography is nowadays applied especially on the liver and breast, but the technique has been increasingly used for other tissues including the thyroid, lymph nodes, spleen, pancreas, gastrointestinal tract, kidney, prostate, and the musculoskeletal and vascular systems. This book presents some of the applications of strain and shear-wave ultrasound elastography in hepatic, pancreatic, breast, and musculoskeletal conditions

The use of two-dimensional shear wave elastography in people with obesity for the assessment of liver fibrosis in non-alcoholic fatty liver disease

Obesity is associated with significant comorbidities, including non-alcoholic fatty liver disease (NAFLD). Given its potential to progress to advanced liver disease, monitoring the extent and progress of liver fibrosis and assessing its fibrosis stage are essential. Although liver biopsy is considered to be the gold standard for liver fibrosis staging, it is an invasive procedure with risk of complications. Considering the rising prevalence of obesity and NAFLD globally, developing non-invasive diagnostic methods is a priority. Transient elastography (TE) is increasingly being used to assess the severity of liver disease. However, in the presence of severe obesity, the increased thickness of subcutaneous adipose tissue and changes in anatomy may affect its diagnostic accuracy. Two-dimensional shear wave elastography (2D-SWE) assesses the liver stiffness in real time along with simultaneous anatomic B-mode ultrasound imaging and allows selection of the region of interest. This would suggest that 2D-SWE has several advantages over TE in patients with severe obesity. The purpose of this review is to examine the current literature addressing the use of 2D-SWE in the assessment of liver fibrosis in patients with NAFLD. This review also examines the evidence on the use of 2D-SWE in patients with obesity and NAFLD and compares it to TE as a novel and non-invasive method of assessing liver fibrosis

비알코올성 지방간 환자에서 정량적 초음파 영상 지표의 개발 및 지방간 진단능 평가

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 이정민.Purpose: To investigate the diagnostic performance of quantitative ultrasound (QUS) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Materials and methods: In this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. Participants underwent ultrasound (US) examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, attenuation coefficient (AC) at tissue attenuation imaging (TAI) and scatter-distribution coefficient (SC) at tissue scatter-distribution imaging (TSI) were measured. Correlation between the QUS parameters (AC and SC) and MRI-PDFF was evaluated using Pearson correlation coefficients. Diagnostic performance of AC at TAI and SC at TSI for detecting hepatic steatosis (MRI-PDFF ≥5%) and hepatic fat content ≥10% (MRI-PDFF ≥10%) were assessed by receiver operating characteristic (ROC) analysis. Significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis. Results: Participants were classified with MRI-PDFF <5% (n=38), 5-10% (n=23), and ≥10% (n=59). AC at TAI and SC at TSI were significantly correlated with MRI-PDFF (r=0.659 and 0.727, P<0.001 for both). For detecting hepatic steatosis and hepatic fat content ≥10%, the area under the ROC curves (AUCs) of AC at TAI were 0.861 (95% confidence interval [CI]: 0.786-0.918) and 0.835 (95% CI: 0.757-0.897), and of SC at TSI were 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972), respectively. In multivariate linear regression analysis, MRI-PDFF was an independent determinant of AC at TAI and SC at TSI. Conclusion: AC at TAI and SC at TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.배경 및 목적: 본 연구에서는 비알코올성 지방간 환자에서 지방간 정도를 평가하기 위한 정량적 초음파 지표를 개발하고, 자기공명영상 양성자밀도 지방분율을 기준으로 하여 정량적 초음파 지표의 지방간 진단능을 평가하고자 한다. 재료 및 방법: 본 단일센터 전향적 연구에서는 2019년 3월부터 2020년 1월까지 임상적으로 비알코올성 지방간이 의심되는 환자와 간이식 공여자를 포함한 총 120명의 참가자가 등록되었다. 참가자들은 무선주파수 (radiofrequency, RF) 데이터를 얻기 위한 초음파 검사와 자기공명영상 양성자밀도 지방분율(Magnetic resonance imaging proton density fat fraction, MRI-PDFF) 검사를 시행하였다. 초음파 RF 데이터를 분석하여, 조직감쇠영상(tissue attenuation imaging, TAI)에서의 감쇠계수 (attenuation coefficient, AC)와 조직 산란분포 영상(tissue scatter-distribution imaging, TSI)에서의 산란분포계수 (scatter-distribution coefficient, SC)를 획득하였다. 이 두 정량적 초음파 지표 (AC, SC)와 자기공명영상 양성자밀도 지방분율(MRI-PDFF) 사이의 연관성을 피어슨 상관계수를 통해 분석하였다. 정량적 초음파 지표들이 MRI-PDFF ≥5% 와 MRI-PDFF ≥10%의 지방간을 진단하는 진단능을 Receiver operating characteristics (ROC) 분석을 통해 확인하였다. 또한, 다변량 회귀분석(multivariate linear regression analysis)을 통해, 두 정량적 초음파 지표에 영향을 주는 임상 또는 영상적 지표를 확인하였다. 결과: 참가자는 지방간 정도에 따라 세 단계로 구분되었다 (MRI-PDFF <5% (n=38), 5-10% (n=23), and ≥10% (n=59)). 감쇠계수 (AC at TAI)와 산란분포계수 (SC at TSI)는 자기공명영상 양성자밀도 지방분율과 강한 상관관게를 보였다 (r=0.659 and 0.727, P<0.001 for both). 지방간 유무 진단 (MRI-PDFF ≥5%)과 MRI-PDFF ≥10%의 지방간진단에 있어 감쇠계수의 진단능은 0.861 (95% confidence interval [CI]: 0.786-0.918) 과 0.835 (95% CI: 0.757-0.897)이었고, 산란분포계수의 진단능은 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972) 이었다. 다변량회귀분석에서 지방분율이 정량적 초음파 지표와 연관성을 보이는 유일한 독립적인 인자로 확인되었다. 결론: 본 연구에서 감쇠계수 (AC at TAI)와 산란분포계수 (SC at TSI)는 자기공명영상 양성자 지방분율과 높은 상관성을 보였고, 지방간의 진단과 그 정도를 확인하는데 있어 높은 진단능을 보였다.Abstract -----------------------1 Contents -----------------------3 List of Tables -----------------4 List of Figures -----------------5 Introduction -----------------6 I. Pilot study -----------------8 Materials and Methods ---- 8 Results ----------------------13 II. Main study ----------------15 Materials and Methods --- 15 Results ----------------------22 Discussion ----------------25 References ----------------30 Tables ----------------------35 Figures ----------------------43 Appendix --------------- 46 Abstract in Korean --------- 49Docto

The Impact of Lifestyle Medicine on Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The main risk factor for the development of NAFLD is metabolic syndrome. Women are at greatest risk, typically in their 5th to 6th decade of life. The more aggressive form of NAFLD is nonalcoholic steatohepatitis (NASH) which is characterized by inflammation associated with NAFLD. NASH has the greatest tendency to progress into cirrhosis. However, lifestyle intervention has been shown to effectively treat, and even reverse NAFLD. The purpose of this quantitative, quasi-experimental study was to lend additional research and demonstrate improvement in NAFLD through lifestyle intervention with 1) a Mediterranean diet, high in fiber and low in saturated fat, 2) moderate exercise with walking 90 minutes per week, and 3) social support group meetings once monthly over a six-month period. Outcomes were measured by 1) 5% total body weight (TBW) loss, 2) improved hepatic steatosis as measured by ultrasound, and 3) improved serum fibrosis staging. There were 20 participants, with a mean age of 53.55 years. Participants were 85% female, 15% male, 85% Caucasian, 10% African American, and 5% Hispanic. They received education on a Mediterranean diet, agreed to walk 90 minutes each week, and attended six support group meetings over a six-month period. At the end of six months, 90% of participants achieved 5% TBW loss. Diet adherence was shown to be statistically significant to the prediction of percentage of TBW loss. However, walking and group meeting attendance were not statistically significant to the prediction of percentage of TBW loss. With regard to ultrasound outcomes, diet and walking adherence were not found to be statistically significant; still, diet adherence was noted to make a person 1.75 times more likely to have a positive ultrasound outcome, with improved fibrosis. Improved post-intervention serum fibrosis scores were found to be statistically significant. After careful SCHOLARLY PROJECT 4 consideration, the greatest limitation of this study was size. This study was too small to accurately measure the power of all of the independent variables and their impact on NAFLD. Future studies should include a larger, more diverse population, and be conducted over a longer period of time. Future studies would also benefit from a multi-disciplinary team approach. Despite the limitations, the knowledge gained from this research will help shape and advance current clinical guidelines. Nurse Practitioners (NPs) serve as leaders in lifestyle medicine. NPs are vital to advancing research and studying the impact lifestyle medicine has on chronic disease, such as NAFLD. Keywords: NAFLD, NASH, fibrosis, cirrhosis, exercise, diet, social support in treatment of chronic disease, weight loss, metabolic syndrome, T2DM, dietary modification, Mediterranean diet, hyperlipidemia and liver disease, lifestyle modification, lifestyle medicine, diagnosis, and treatment of NAFL

Ultrasound Elastography

The comparison between methods, evaluation of portal hypertension and many other questions are still open issues in liver elastography. New elastographic applications are under evaluation and close to being used in clinical practice. Strain imaging has been incorporated into many disciplines and EFSUMB guidelines are under preparation. More research is necessary for improved evidence for clinical applications in daily practice. The Special Issue published papers on recent advances in development and application of Ultrasound Elastography