Papers by Claude B. Sirlin
Nutrients
Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the deve... more Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) an...
Abdominal Radiology, 2021
To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat f... more To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF. This was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly (“balanced”) were compared with those that did not (“unbalanced”) using two-sample t tests. The 29 enrolled subjects (23 male, mean age 24 years) had mean 9-ROI PDFF 11.8% (1.1–36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC < 1%, 50 (83%) achieved inter-exam RC < 1%, and all (100%) achieved MAE < 1%. Balanced sampling strategies had higher ICCs and lower RCs, and lower MAEs than unbalanced strategies in aggregate (p < 0.001 for comparisons between balanced vs. unbalanced strategies). Repeatability improves and error diminishes with more ROIs. Balanced 4-ROI strategies provide high repeatability and low error.
European Radiology, 2021
Objectives To assess reproducibility and fibrosis classification accuracy of magnetic resonance e... more Objectives To assess reproducibility and fibrosis classification accuracy of magnetic resonance elastography (MRE)–determined liver stiffness measured manually at two different centers, and by automated analysis software in adults with nonalcoholic fatty liver disease (NAFLD), using histopathology as a reference standard. Methods This retrospective, cross-sectional study included 91 adults with NAFLD who underwent liver MRE and biopsy. MRE-determined liver stiffness was measured independently for this analysis by an image analyst at each of two centers using standardized manual analysis methodology, and separately by an automated analysis. Reproducibility was assessed pairwise by intraclass correlation coefficient (ICC) and Bland-Altman analysis. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analyses. Results ICC of liver stiffness measurements was 0.95 (95% CI: 0.93, 0.97) between center 1 and center 2 analysts, 0.96 (95% CI: 0.94, 0.97) between the ce...
European Radiology, 2021
Objectives To compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic re... more Objectives To compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic resonance elastography (MRE) for classifying fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). Methods Patients from a prospective single-center cohort with clinical liver biopsy for known or suspected NAFLD underwent contemporaneous SWE and MRE. AUCs for classifying biopsy-determined liver fibrosis stages ≥ 1, ≥ 2, ≥ 3, and = 4, and their respective performance parameters at cutoffs providing ≥ 90% sensitivity or specificity were compared between SWE and MRE. Results In total, 100 patients (mean age, 51.8 ± 12.9 years; 46% males; mean BMI 31.6 ± 4.7 kg/m2) with fibrosis stage distribution (stage 0/1/2/3/4) of 43, 36, 5, 10, and 6%, respectively, were included. AUCs (and 95% CIs) for SWE and MRE were 0.65 (0.54–0.76) and 0.81 (0.72–0.89), 0.81 (0.71–0.91) and 0.94 (0.89–1.00), 0.85 (0.74–0.96) and 0.95 (0.89–1.00), and 0.91 (0.79–1.00) and 0.92 (0.83–1.00), for dete...
2020 IEEE International Ultrasonics Symposium (IUS), 2020
Quantitative ultrasound (QUS) techniques are diagnostically useful in assessing nonalcoholic fatt... more Quantitative ultrasound (QUS) techniques are diagnostically useful in assessing nonalcoholic fatty liver disease (NAFLD). From previous studies, the backscatter coefficient (BSC) correlates with liver fat fraction, but the mechanisms have not been determined. Understanding the ultrasound scattering mechanisms will lead to better acoustic scattering models and more accurate diagnostics. The purpose of this study is to test the following hypothesis: Fat droplet deposition in hepatocytes alters the locations of hepatocyte nuclei, changing the spatial distribution of the nuclei, which leads to the change in the structure function (SF), a factor of the BSC. The SF, determined by the distribution of the nuclei, is correlated with the fat fraction. To test this hypothesis, hematoxylin and eosin-stained liver histopathological slides from 48 participants were digitized (40×). One to 5 regions (453.6 µm × 453.6 µm) were selected from each participant's slide(s), yielding 218 images in to...
Augmented Reality is used in Image Guided surgery (AR IG) to fuse surgical landmarks from preoper... more Augmented Reality is used in Image Guided surgery (AR IG) to fuse surgical landmarks from preoperative images into a video overlay. Physical simulation is essential to maintaining accurate position of the landmarks as surgery progresses and ensuring patient safety by avoiding accidental damage to vessels etc. In liver procedures, AR IG simulation accuracy is hampered by an inability to model stiffness variations unique to the patients disease. We introduce a novel method to account for patient specific stiffness variation based on Magnetic Resonance Elastography (MRE) data. To the best of our knowledge we are the first to demonstrate the use of in-vivo biomechanical data for AR IG landmark placement. In this early work, a comparative evaluation of our MRE data driven simulation and the traditional method shows clinically significant differences in accuracy during landmark placement and motivates further animal model trials.
European Journal of Radiology, 2020
Purpose-To develop and evaluate the performance of a fully-automated convolutional neural network... more Purpose-To develop and evaluate the performance of a fully-automated convolutional neural network (CNN)-based algorithm to evaluate hepatobiliary phase (HBP) adequacy of gadoxetate disodium (EOB)-enhanced MRI. Secondarily, we explored the potential of the proposed CNN algorithm to reduce examination length by applying it to EOB-MRI examinations.
Abdominal Radiology, 2019
Journal of Magnetic Resonance Imaging, 2019
Liver fibrosis is a histological hallmark of most chronic liver diseases, can progress to cirrhos... more Liver fibrosis is a histological hallmark of most chronic liver diseases, can progress to cirrhosis and liver failure, and predisposes to hepatocellular carcinoma. Accurate diagnosis of liver fibrosis is necessary for prognosis, risk-stratification, and treatment decision-making. Liver biopsy, the reference standard for assessing liver fibrosis, is invasive, costly, and impractical for surveillance and treatment response monitoring. Elastography offers a noninvasive, objective, and quantitative alternative to liver biopsy. This article discusses the need for noninvasive assessment of liver fibrosis and reviews the comparative advantages and limitations of US and MR elastography techniques with respect to their basic concepts, acquisition, processing, and diagnostic performance. Variations in clinical contexts of use and common pitfalls associated with each technique are considered. In addition, current challenges and future directions to improve the diagnostic accuracy and clinical utility of elastography techniques are discussed.
Abdominal Radiology, 2018
PurposeTo determine the inter-reader agreement of magnetic resonance imaging proton density fat f... more PurposeTo determine the inter-reader agreement of magnetic resonance imaging proton density fat fraction (PDFF) and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis (NASH).Study typeWe performed a secondary analysis of a placebo-controlled randomized clinical trial of a bile acid sequestrant in 45 adults with NASH. A six-echo spoiled gradient-recalled-echo magnitude-based fat quantification technique was performed at 3 T. Three independent readers measured MRI-PDFF by placing one primary and two additional regions of interest (ROIs) in each segment at both time points. Cross-sectional agreement between the three readers was evaluated using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Additionally, we used Bland–Altman analyses to examine pairwise agreement between the three readers at baseline, end of treatment (EOT), and for longitudinal change.ResultsUsing all ROIs by all readers, mean PDFF at baseline, at EOT, and mean change in PDFF was 16.1%, 16.0%, and 0.07%, respectively. The 27-ROI PDFF measurements had 0.998 ICC and 1.8% CV at baseline, 0.998 ICC and 1.8% CV at EOT, and 0.997 ICC for longitudinal change. The 9-ROI PDFF measurements had corresponding values of 0.997 and 2.6%, 0.996 and 2.4%, and 0.994. Using 27 ROIs, the magnitude of the bias between readers for whole-liver PDFF measurement ranged from 0.03% to 0.06% points at baseline, 0.01% to 0.07% points at EOT, and 0.01% to 0.02% points for longitudinal change.ConclusionInter-reader agreement for measuring whole-liver PDFF and its longitudinal change is high. 9-ROI measurements have only slightly lower agreement than 27-ROI measurements.
Journal of Magnetic Resonance Imaging, 2019
Background: Quantitative-chemical-shift-encoded (CSE)-magnetic resonance imaging (MRI) methods ha... more Background: Quantitative-chemical-shift-encoded (CSE)-magnetic resonance imaging (MRI) methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated.
Journal of hepatology, 2019
Non-invasive tools for monitoring treatment response and disease progression in non-alcoholic ste... more Non-invasive tools for monitoring treatment response and disease progression in non-alcoholic steatohepatitis (NASH) are needed. Our objective was to evaluate the utility of magnetic resonance (MR)-based hepatic imaging measures for the assessment of liver histology in patients with NASH. We analyzed data from patients with NASH and stage 2 or 3 fibrosis enrolled in a phase II study of selonsertib. Pre- and post-treatment assessments included centrally read MR elastography (MRE)-estimated liver stiffness, MR imaging-estimated proton density fat fraction (MRI-PDFF), and liver biopsies evaluated according to the NASH Clinical Research Network classification and the non-alcoholic fatty liver disease activity score (NAS). Among 54 patients with MRE and biopsies at baseline and week 24, 18 (33%) had fibrosis improvement (≥1-stage reduction) after undergoing 24 weeks of treatment with the study drug. The area under the receiver operating characteristic curve (AUROC) of MRE-stiffness to pr...
Topics in Magnetic Resonance Imaging, 2017
Fatty liver disease is characterized histologically by hepatic steatosis, the abnormal accumulati... more Fatty liver disease is characterized histologically by hepatic steatosis, the abnormal accumulation of lipid in hepatocytes. It is classified into alcoholic fatty liver disease and non-alcoholic fatty liver disease, and is an increasingly important cause of chronic liver disease and cirrhosis. Assessing the severity of hepatic steatosis in these conditions is important for diagnostic and prognostic purposes, as hepatic steatosis is potentially reversible if diagnosed early. The gold standard for assessing hepatic steatosis is liver biopsy, which is limited by sampling error, its invasive nature, and associated morbidity. As such, non-invasive imaging-based methods of assessing hepatic steatosis are needed. Ultrasound and CT are able to suggest the presence of hepatic steatosis based on imaging features, but are unable to accurately quantify hepatic fat content. Since Dixon's seminal work in 1984, MRI has been used to compute the signal fat fraction from chemical-shift-encoded imaging, commonly implemented as out-of-phase and in-phase imaging. However, signal fat fraction is confounded by several factors that limit its accuracy and reproducibility. Recently, advanced chemical-shift-encoded MRI methods have been developed that address these confounders and are able to measure the proton density fat fraction (PDFF), a standardized, accurate, and reproducible biomarker of fat content. The use of these methods in the liver, as well as in other abdominal organs such as the pancreas, adrenal glands, and adipose tissue will be discussed in this review.
Abdominal radiology (New York), Jan 28, 2018
The purpose of the study is to assess the reader agreement and accuracy of eight ultrasound imagi... more The purpose of the study is to assess the reader agreement and accuracy of eight ultrasound imaging features for classifying hepatic steatosis in adults with known or suspected hepatic steatosis. This was an IRB-approved, HIPAA-compliant prospective study of adult patients with known or suspected hepatic steatosis. All patients signed written informed consent. Ultrasound images (Siemens S3000, 6C1HD, and 4C1 transducers) were acquired by experienced sonographers following a standard protocol. Eight readers independently graded eight features and their overall impression of hepatic steatosis on ordinal scales using an electronic case report form. Duplicated images from the 6C1HD transducer were read twice to assess intra-reader agreement. Intra-reader, inter-transducer, and inter-reader agreement were assessed using intraclass correlation coefficients (ICC). Features with the highest intra-reader agreement were selected as predictors for dichotomized histological steatosis using Clas...
European radiology, Jan 16, 2018
The 2017 Core of the computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Repo... more The 2017 Core of the computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) provides clear definitions and concise explanations of the CT/MRI diagnostic algorithm. Nevertheless, there remain some practical and controversial issues that radiologists should be aware of when using the system. This article discusses pitfalls and problems which may be encountered when the version 2017 diagnostic algorithm is used for CT and MRI. The pitfalls include challenges in applying major features and assigning the LR-M category, as well as categorisation discrepancy between CT and MRI. The problems include imprecision of category codes, application of ancillary features, and regional practice variations in hepatocellular carcinoma (HCC) diagnosis. Potential solutions are presented along with these pitfalls and problems. • Although the diagnostic algorithm provides clear and detailed explanations, major feature evaluation can be subject to pitfal...
Abdominal Radiology, 2018
This article provides a glimpse into the future of the Liver Imaging Reporting and Data System (L... more This article provides a glimpse into the future of the Liver Imaging Reporting and Data System (LI-RADS), discussing the immediate and long-term plans for its continuing improvement and expansion. To complement the Core and Essentials components of the latest version of LI-RADS, a comprehensive manual will be released soon, and it will include technical recommendations, management guidance, as well as reporting instructions and templates. In this article, we briefly review the process by which LI-RADS has been developed until now, a process guided by a variable combination of data, expert opinion, and desire for congruency with other diagnostic systems in North America. We then look forward, envisioning that forthcoming updates to LI-RADS will occur regularly every 3 to 5 years, driven by emerging high-quality scientific evidence. We highlight some of the key knowledge and technology gaps that will need to be addressed to enable the needed refinements. We also anticipate future expansions in scope to meet currently unaddressed clinical needs. Finally, we articulate a vision for eventual unification of imaging system for HCC screening and surveillance, diagnosis and staging, and treatment response assessment.
World journal of hepatology, Jan 27, 2018
Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease, with a worldw... more Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic liver injury and progressive fibrosis in a significant minority. Effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard; however, non-invasive imaging methods are rapidly evolving and may replace biopsy in some circumstances. These methods include well-established techniques, such as conventional ultrasonography, computed tomography, and magnetic resonance imaging and newer imaging technologies, such as ultrasound elastography, quantitative ultrasound techniques, magnetic resonance elastography, and magnetic resonance-based fat quantitation techniques...
Abdominal radiology (New York), Jan 28, 2018
The Liver Imaging and Reporting Data System (LI-RADS) is a comprehensive system for standardizing... more The Liver Imaging and Reporting Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging with the overarching goal of improving communication, clinical care, education, and research relating to patients at risk for or diagnosed with hepatocellular carcinoma (HCC). In 2018, the American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its clinical practice guidance for the imaging-based diagnosis of HCC. The harmonization between the AASLD and LI-RADS diagnostic imaging criteria required minor modifications to the recently released LI-RADS v2017 guidelines, necessitating a LI-RADS v2018 update. This article provides an overview of the key changes included in LI-RADS v2018 as well as a look at the LI-RADS v2018 diagnostic algorithm and criteria, technical recommendations, and management suggestions. Substantive changes in LI-RADS v2018 are the removal of the ...
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Papers by Claude B. Sirlin