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Background & aimsNon-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement.MethodsAdult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI.ResultsTreatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively).ConclusionsIn adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF.Clinical trial numberNCT01265498.Impact and implicationsAlthough central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

PurposeChemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study.Theory and methodsA technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature.ResultsSimulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction.ConclusionCorrection for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.

BackgroundThe liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates.PurposeTo identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD).Study typeRetrospective analysis of prospectively acquired data.PopulationBaseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials.Field strength1.5T and 3T; chemical-shift encoded multiecho gradient echo.AssessmentCorrelation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*.Statistical testsPearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method.ResultsHepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P