Image Correction Methods for Regions of Interest of Cirrhosis Liver Classification on CNNs

The average error rate in liver cirrhosis classification on B-mode ultrasound images using the traditional pattern recognition approach is still too high. In order to improve the liver cirrhosis classification performance, image correction methods and a convolution neural network (CNN) approach are focused on. The impact of image correction methods on region of interest (ROI) images that are input into the CNN for the purpose of classifying liver cirrhosis based on data from B-mode ultrasound images is investigated. In this paper, image correction methods based on tone curves are developed. The experimental results show positive benefits from the image correction methods by improving the image quality of ROI images. By enhancing the image contrast of ROI images, the image quality improves and thus the generalization ability of the CNN also improves

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

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

Computer-Assisted Algorithms for Ultrasound Imaging Systems

Ultrasound imaging works on the principle of transmitting ultrasound waves into the body and reconstructs the images of internal organs based on the strength of the echoes. Ultrasound imaging is considered to be safer, economical and can image the organs in real-time, which makes it widely used diagnostic imaging modality in health-care. Ultrasound imaging covers the broad spectrum of medical diagnostics; these include diagnosis of kidney, liver, pancreas, fetal monitoring, etc. Currently, the diagnosis through ultrasound scanning is clinic-centered, and the patients who are in need of ultrasound scanning has to visit the hospitals for getting the diagnosis. The services of an ultrasound system are constrained to hospitals and did not translate to its potential in remote health-care and point-of-care diagnostics due to its high form factor, shortage of sonographers, low signal to noise ratio, high diagnostic subjectivity, etc. In this thesis, we address these issues with an objective of making ultrasound imaging more reliable to use in point-of-care and remote health-care applications. To achieve the goal, we propose (i) computer-assisted algorithms to improve diagnostic accuracy and assist semi-skilled persons in scanning, (ii) speckle suppression algorithms to improve the diagnostic quality of ultrasound image, (iii) a reliable telesonography framework to address the shortage of sonographers, and (iv) a programmable portable ultrasound scanner to operate in point-of-care and remote health-care applications

State-of-the-art MR imaging in the work-up of primary hepatocellular tumors

Magnetic resonance (MR) imaging is an imaging modality that has evolved rapidly in the past two decades. The development of advanced hardware and new sophisticated pulse sequences have allowed faster imaging, with increased temporal and spatial resolution. This has resulted in the development and implementation of new acquisition techniques that facilitate improved visualisation of neoplastic processes. In addition, faster sequences enable multiphasic dynamic imaging after intravenous administration of contrast material, which results in better tumor characterisation and improved diagnostic confidence by the reading radiologist. The radiol

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

New insights along the gut-liver axis in cardiometabolic disease

In this thesis we targeted the human gut microbiome for the development of therapeutic strategies in metabolic disorders. In chapter 3 we performed a randomized placebo-controlled cross-over study in individuals with the metabolic syndrome in which we showed that a single duodenal infusion of A. soehngenii improved peripheral glycemic control. In chapter 4 we studied the effect of a 2 weeks oral A. soehngenii treatment in individuals with T2D treated with metformin on their glycemic control.The second part of the thesis focused on MASLD, currently the most common cause of chronic liver dysfunction worldwide. In chapter 5 we reviewed the gut microbial and gut microbial-derived metabolite signatures associated with the development and disease progression of MASLD. To dissect causality of intestinal microbiota in MASLD, in chapter 6 we performed a single-center, double-blind, randomized controlled proof-of-principle pilot study comparing the effect of three 8-weekly lean vegan donor FMT versus autologous FMT on the severity of MASLD, using liver biopsies in individuals with hepatic steatosis on ultrasound. Moreover, we aimed to identify and validate noninvasive diagnostic methods in disease progression in MASLD. Hence, in chapter 7 we examined the diagnostic performance of multiparametric MRI for the assessment of disease severity along the MASLD disease spectrum with comparison to histological scores