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    Claude B. Sirlin

    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... 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...
    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... 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.
    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... 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...
    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... 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...
    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... 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 preoperative images into a video overlay. Physical simulation is essential to maintaining accurate position of the landmarks as surgery progresses... 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.
    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... 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.
    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... 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...
    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... 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...
    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... 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...
    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... 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.
    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... 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...
    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... 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 ...
    Patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic; steatohepatitis (NASH) often require histologic assessment via liver biopsy. Magnetic; resonance imaging (MRI)-based methods for measuring liver triglycerides based... more
    Patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic; steatohepatitis (NASH) often require histologic assessment via liver biopsy. Magnetic; resonance imaging (MRI)-based methods for measuring liver triglycerides based on proton density fat fraction (PDFF) are increasingly as a non-invasive tool to identify patients with hepatic steatosis and to assess for change in liver fat over time. We aimed to determine whether MRI-PDFF accurately reflects a variety of liver histology features in patients with NAFLD or NASH. We performed a retrospective analysis of pooled data from 3 phase 2a trials of pharmacotherapies for NAFLD or NASH. We collected baseline clinical, laboratory, and histopathology data on all subjects who had undergone MRI analysis in 1 of the trials. We assessed the relationship between liver PDFF values and liver histologic findings using correlation and area under the receiver operating characteristic (AUROC) analyses. As an ancillary analysis, we also s...
    Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques for detection of liver fibrosis. Single-center studies have compared the diagnostic performance of MRE vs TE in patients with nonalcoholic... more
    Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques for detection of liver fibrosis. Single-center studies have compared the diagnostic performance of MRE vs TE in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pooled analysis of individual participant data from published studies to compare the diagnostic performance of MRE vs TE for staging of liver fibrosis in patients with NAFLD, using liver biopsy as reference. We performed a systematic search of publication databases, from 2005 through 2017. We identified 3 studies of adults with NAFLD who were assessed by MRE, TE, and liver biopsy. In a pooled analysis, we calculated the cluster-adjusted area under the curve (AUROC) of MRE and TE for the detection of each stage of fibrosis. AUROC comparisons between MRE and TE were performed using the Delong test. Our pooled analysis included 230 participants with biopsy-proven NAFLD with mean age of 52.2±13.9 years and a bod...
    Previous studies have shown that gut-microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites, especially those derived from the gut-microbiome, have a shared gene-effect with... more
    Previous studies have shown that gut-microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites, especially those derived from the gut-microbiome, have a shared gene-effect with hepatic steatosis and fibrosis. This is a cross-sectional analysis of a prospective discovery cohort including 156 well-characterized twins and families with untargeted metabolome profiling assessment. Hepatic steatosis was assessed using magnetic-resonance-imaging proton-density-fat-fraction (MRI-PDFF) and fibrosis using MR-elastography (MRE). A twin additive genetics and unique environment effects (AE) model was used to estimate the shared gene-effect between metabolites and hepatic steatosis and fibrosis. The findings were validated in an independent prospective validation cohort of 156 participants with biopsy-proven NAFLD including shotgun metagenomics sequencing assessment in a subgroup of the cohort. In the discovery cohort, 56 metabolites includin...
    Improving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients... more
    Improving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis. To assess the accuracy of high SNR (Hi-SNR) MRI-C versus standard MRI-C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard. Prospective. In all, 231 adult and pediatric patients with known or suspected NAFLD. PDFF estimated at 3T by three MR techniques: standard MRI-C; a Hi-SNR MRI-C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard). MRI-PDFF was measured by image analysts using a region of interest coregistered with the MRS-PDFF voxel. Linear regression analyses were used to assess accuracy and precision of MRI-estimated PDFF for MRS-PDFF as a fun...
    Increased de novo lipogenesis (DNL) contributes to the pathogenesis of nonalcoholic steatohepatitis (NASH). Acetyl-CoA carboxylase catalyzes the rate-limiting step in DNL. We evaluated the safety and efficacy of GS 0976, a small molecule... more
    Increased de novo lipogenesis (DNL) contributes to the pathogenesis of nonalcoholic steatohepatitis (NASH). Acetyl-CoA carboxylase catalyzes the rate-limiting step in DNL. We evaluated the safety and efficacy of GS 0976, a small molecule inhibitor of acetyl-CoA carboxylase, in patients with NASH. In an open-label prospective study, patients with NASH (n=10) received GS-0976 20 mg orally once daily for 12 weeks. NASH was diagnosed based on a proton density fat fraction estimated by magnetic resonance imaging (MRI-PDFF) >10% and liver stiffness by magnetic resonance elastography (MRE) >2.88 kPa. The contribution from hepatic DNL to plasma palmitate was measured by 14 days of heavy water labeling before and at the end of treatment. We performed the same labelling protocol in an analysis of healthy volunteers who were not given DNL (controls, n=10). MRI-PDFF and MRE at baseline, and at weeks 4 and 12 of GS-0976 administration, were measured. We analyzed markers of liver injury and...
    The computed tomography / magnetic resonance imaging (CT/MRI) Liver Imaging Reporting & Data System (LI-RADS) is a standardized system for diagnostic imaging terminology, technique, interpretation, and reporting in patients with or at... more
    The computed tomography / magnetic resonance imaging (CT/MRI) Liver Imaging Reporting & Data System (LI-RADS) is a standardized system for diagnostic imaging terminology, technique, interpretation, and reporting in patients with or at risk for developing hepatocellular carcinoma (HCC). Using diagnostic algorithms and tables, the system assigns to liver observations category codes reflecting the relative probability of HCC or other malignancies. This review article provides an overview of the 2017 version of CT/MRI LI-RADS with a focus on MRI. The main LI-RADS categories and their application will be described. Changes and updates introduced in this version of LI-RADS will be highlighted, including modifications to the diagnostic algorithm and to the optional application of ancillary features. Comparisons to other major diagnostic systems for HCC will be made, emphasizing key similarities, differences, strengths, and limitations. In addition, this review presents the new Treatment Re...
    Markers are needed to predict progression of nonalcoholic fatty liver disease (NAFLD). The proton density fat fraction, measured by magnetic resonance imaging (MRI-PDFF), provides an accurate, validated marker of hepatic steatosis.... more
    Markers are needed to predict progression of nonalcoholic fatty liver disease (NAFLD). The proton density fat fraction, measured by magnetic resonance imaging (MRI-PDFF), provides an accurate, validated marker of hepatic steatosis. However, it is not clear whether the proton density fat fraction identifies patients at risk for NAFLD progression. We performed a follow-up study of 95 well-characterized patients with biopsy-proven NAFLD and examined the association between liver fat content and fibrosis progression. MRI-PDFF measurements were made at study entry (baseline). Biopsies were collected from patients at baseline and after a mean time period of 1.75 years. Among patients with no fibrosis at baseline, a higher proportion of patients in the higher liver fat group (MRI-PDFF ≥ 15.7%) had fibrosis progression (38.1%) than in the lower liver fat group (11.8%) (P=.067). In multivariable-adjusted logistic regression models (adjusted for age, sex, ethnicity, and body mass index), pati...
    Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically... more
    Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically relevant. Traditionally, liver biopsy has been the method of choice for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods have become a key research interest in the field. Elastography enables the noninvasive measurement of tissue mechanical properties through observation of shear-wave propagation in the tissue of interest. Increasing fibrosis stage is associated with increased liver stiffness, providing a discriminatory feature that can be exploited by elastographic methods. Ultrasonographic (US) and magnetic resonance (MR) imaging elastographic methods are commercially available, each with their respective strengths and limitations. Here, the authors review the technical basis, acquisition techniques, and results and lim...
    The purpose of this work was to investigate sources of bias in magnetic resonance imaging (MRI) liver fat quantification that lead to a dependence of the proton density fat fraction (PDFF) on the number of echoes. This was a retrospective... more
    The purpose of this work was to investigate sources of bias in magnetic resonance imaging (MRI) liver fat quantification that lead to a dependence of the proton density fat fraction (PDFF) on the number of echoes. This was a retrospective analysis of liver MRI data from 463 subjects. The magnitude signal variation with TE from spoiled gradient echo images was curve fitted to estimate the PDFF using a model that included monoexponential R* decay and a multi-peak fat spectrum. Additional corrections for non-exponential decay (Gaussian), bi-exponential decay, degree of fat saturation, water frequency shift and noise bias were introduced. The fitting error was minimized with respect to 463 × 3 = 1389 subject-specific parameters and seven additional parameters associated with these corrections. The effect on PDFF was analyzed, notably the dependence on the number of echoes. The effects on R* were also analyzed. The results showed that the inclusion of bias corrections resulted in an incr...
    Nonalcoholic fatty liver disease (NAFLD) is an epidemic in the obese population. Bariatric surgery is known to reverse multiple metabolic complications of obesity such as diabetes, dyslipidemia, and NAFLD, but the timing of liver changes... more
    Nonalcoholic fatty liver disease (NAFLD) is an epidemic in the obese population. Bariatric surgery is known to reverse multiple metabolic complications of obesity such as diabetes, dyslipidemia, and NAFLD, but the timing of liver changes has not been well described. This was an IRB-approved, two-institutional prospective study. Bariatric patients received MRIs at baseline and after a pre-operative liquid diet. Liver biopsies were performed during surgery and if NAFLD positive, the patients received MRIs at 1, 3, and 6 months. Liver volumes and proton-density fat fraction (PDFF) were calculated from offline MRI images. Primary outcomes were changes in weight, body mass index (BMI), percent excess weight loss (EWL%), liver volume, and PDFF. Resolution of steatosis, as defined as PDFF < 6.4% based on previously published cutoffs, was assessed. Secondarily, outcomes were compared between patients who underwent laparoscopic sleeve gastrectomy (LSG) versus laparoscopic Roux-en-Y gastri...
    The Liver Imaging Reporting and Data System (LI-RADS) is a reporting system created for the standardized interpretation of liver imaging findings in patients who are at risk for hepatocellular carcinoma (HCC). This system was developed... more
    The Liver Imaging Reporting and Data System (LI-RADS) is a reporting system created for the standardized interpretation of liver imaging findings in patients who are at risk for hepatocellular carcinoma (HCC). This system was developed with the cooperative and ongoing efforts of an American College of Radiology-supported committee of diagnostic radiologists with expertise in liver imaging and valuable input from hepatobiliary surgeons, hepatologists, hepatopathologists, and interventional radiologists. In this article, the 2017 version of LI-RADS for computed tomography and magnetic resonance imaging is reviewed. Specific topics include the appropriate population for application of LI-RADS; technical recommendations for image optimization, including definitions of dynamic enhancement phases; diagnostic and treatment response categories; definitions of major and ancillary imaging features; criteria for distinguishing definite HCC from a malignancy that might be non-HCC; management op...
    The purpose of this study is to determine the correlation between malignancy risk of focal liver observations in patients at risk for hepatocellular carcinoma (HCC) implied by phrases used in nonstructured radiology reports with the risk... more
    The purpose of this study is to determine the correlation between malignancy risk of focal liver observations in patients at risk for hepatocellular carcinoma (HCC) implied by phrases used in nonstructured radiology reports with the risk inferred by hepatologists. We performed a retrospective review of nonstructured radiology reports issued before Liver Imaging and Reporting Data System (LI-RADS) adoption from four-phase liver CT examinations of patients at risk for HCC. The phrase used by the radiologist in the report impression to describe each focal liver observation was recorded. Five hepatologists independently inferred the LI-RADS category from each phrase. Two abdominal radiologists independently reviewed the images and, blinded to all other information, assigned a LI-RADS category to each observation. Discrepancies were resolved by consensus. One hundred five observations in 77 patients were reported by 23 radiologists using 29 phrases. The most common phrase, "consiste...
    Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques used to detect liver fibrosis in NAFLD. MRE detects fibrosis more accurately than TE, but MRE is more expensive, and the concordance between... more
    Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques used to detect liver fibrosis in NAFLD. MRE detects fibrosis more accurately than TE, but MRE is more expensive, and the concordance between MRE and TE have not been optimally assessed in obese patients. It is important to determine under which conditions TE and MRE produce the same readings, so that some patients can simply undergo TE evaluation to detect fibrosis. We aimed to assess the association between body-mass-index (BMI) and discordancy between MRE and TE findings, using liver biopsy as the reference, and validated our findings in a separate cohort. We performed a cross-sectional study of 119 adults with NAFLD who underwent MRE, TE with M and XL probe, and liver biopsy analysis from October 2011 through January 2017 (training cohort). MRE and TE results were considered to be concordant if they found patients to have the same stage fibrosis as liver biopsy analysis. We validated ...
    The optimal threshold of controlled attenuation parameter (CAP) for the detection of hepatic steatosis using both M and XL probe is unknown in nonalcoholic fatty liver disease (NAFLD). Magnetic resonance imaging... more
    The optimal threshold of controlled attenuation parameter (CAP) for the detection of hepatic steatosis using both M and XL probe is unknown in nonalcoholic fatty liver disease (NAFLD). Magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF) is an accurate and precise method to detect presence of hepatic steatosis and is better than CAP. Thus, the aim of this study was to evaluate the diagnostic accuracy and the optimal threshold of CAP for the detection of hepatic steatosis as defined by MRI-PDFF ≥ 5%. This cross-sectional study included 119 adults (59% women), prospectively recruited with and without NAFLD who underwent MRI-PDFF and CAP using either M probe or XL probe when indicated within a six-month period at the NAFLD Research Center, UCSD. Mean (±standard deviation) age and BMI were 52.4 (±15.2) years and 29.9 (±5.5) kg/m(2) , respectively. The prevalence of NAFLD (MRI-PDFF≥5%) and MRI-PDFF≥ 10% was 70.6% and 47.1%, respectively. The area under the ROC (AUROC) of CAP...
    The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting... more
    The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI...
    Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and... more
    Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and magnetic resonance (MR) imaging, and the potential effect of reader demographics on agreement with a preselected nonconsecutive image set. Materials and Methods Institutional review board approval was obtained, and patient consent was waived for this retrospective study. Ten image sets, comprising 38-40 unique studies (equal number of CT and MR imaging studies, uniformly distributed LI-RADS categories), were randomly allocated to readers. Images were acquired in unenhanced and standard contrast material-enhanced phases, with observation diameter and growth data provided. Readers completed a demographic survey, assigned LI-RADS version 2014 categories, and assessed major features. Intraclass correlation coefficient (ICC) assessed with mixed-model regre...
    A radiologist issuing a LI-RADS category is, implicitly or explicitly, a member of a multidisciplinary team. If the definite diagnosis of a benign or malignant entity is not possible, categorizing the uncertainty as LR-2, -3, -4, or -M... more
    A radiologist issuing a LI-RADS category is, implicitly or explicitly, a member of a multidisciplinary team. If the definite diagnosis of a benign or malignant entity is not possible, categorizing the uncertainty as LR-2, -3, -4, or -M has important management implications. In this article, we discuss the range of options for management or further diagnostic testing and how a LR category may affect the choice between them. We then review recent published data regarding eventual diagnoses following assignment of a LR category.
    Over the past 16 years, several scientific organizations have proposed systems that incorporate imaging for surveillance, diagnosis, staging, treatment, and monitoring of treatment response of hepatocellular carcinoma (HCC). These systems... more
    Over the past 16 years, several scientific organizations have proposed systems that incorporate imaging for surveillance, diagnosis, staging, treatment, and monitoring of treatment response of hepatocellular carcinoma (HCC). These systems are needed to standardize the acquisition, interpretation, and reporting of liver imaging examinations; help differentiate benign from malignant observations; improve consistency between radiologists; and provide guidance for management of HCC. This review article discusses the historical evolution of HCC imaging systems. We indicate the features differentiating these systems, including target population, screening and surveillance algorithm, diagnostic imaging modalities, diagnostic scope, expertise and technical requirements, terminology, major and ancillary imaging features, staging and transplant eligibility, and assessment of treatment response. We highlight the potential benefits of unifying the systems, which we anticipate will enable sharing, pooling, and meta-analysis of data; facilitate multi-center trials; and accelerate dissemination of knowledge.
    To determine the benefit of screening ultrasonography for parenchymal abnormalities as well as free fluid during screening abdominal ultrasonography in patients with blunt trauma. A total of 2693 patients with blunt trauma who were... more
    To determine the benefit of screening ultrasonography for parenchymal abnormalities as well as free fluid during screening abdominal ultrasonography in patients with blunt trauma. A total of 2693 patients with blunt trauma who were triaged to a level 1 trauma center underwent screening abdominal ultrasonography in the resuscitation suite. Examinations were performed by experienced sonographers and included a screen for free intraperitoneal fluid and evaluation of the abdominal organ parenchyma and heart for traumatic injury. Screening ultrasonographic findings were reviewed and compared with findings from autopsy, laparotomy, diagnostic peritoneal lavage, computed tomography, repeated ultrasonography, cystography, and clinical outcome. Imaging studies of all patients with confirmed or suspected injuries were reviewed to identify those in whom parenchymal findings aided diagnosis. One hundred seventy-two patients were found to have evidence of abdominal injury due to blunt trauma on the basis of clinical data, imaging, laparotomy, or autopsy. Forty-four of these patients had no sonographic evidence of hemoperitoneum at the time of initial ultrasonography. Screening ultrasonographic findings were positive for injury in 19 of 44 patients on the basis of parenchymal findings or small retroperitoneal collections of fluid thought to be indicative of trauma. In the remaining 25 patients, screening ultrasonography showed no abnormalities, and injuries were detected by repeated ultrasonography, subsequent computed tomography, or diagnostic peritoneal lavage performed for suspected occult injury on the basis of clinical parameters. In addition, 47 of 126 injured patients with sonographically detected free fluid had parenchymal findings that helped localize injury. Sixteen of those patients were taken to the operating room on the basis of clinical and sonographic findings without undergoing computed tomography. The inability to show injuries with no hemoperitoneum or with delayed hemoperitoneum has been shown to be a limitation of ultrasonography in patients with blunt trauma. In our series, 26% of all patients with documented injuries had no free fluid visible on screening ultrasonography Attention to findings other than free fluid allowed detection in 43% of injured patients without sonographic evidence of hemoperitoneum.

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