Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. METHODS: We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. RESULTS: At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0-1 vs 2-3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91-0.98), and grade 0-2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93-0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2-3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71-0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63-0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. CONCLUSIONS: Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.

Accuracy of PDFF estimation by magnitude-based and complex-based MRI in children with MR spectroscopy as a reference.

PURPOSE: To assess and compare the accuracy of magnitude-based magnetic resonance imaging (MRI-M) and complex-based MRI (MRI-C) for estimating hepatic proton density fat fraction (PDFF) in children, using MR spectroscopy (MRS) as the reference standard. A secondary aim was to assess the agreement between MRI-M and MRI-C. MATERIALS AND METHODS: This was a HIPAA-compliant, retrospective analysis of data collected in children enrolled in prospective, Institutional Review Board (IRB)-approved studies between 2012 and 2014. Informed consent was obtained from 200 children (ages 8-19 years) who subsequently underwent 3T MR exams that included MRI-M, MRI-C, and T1 -independent, T2 -corrected, single-voxel stimulated echo acquisition mode (STEAM) MRS. Both MRI methods acquired six echoes at low flip angles. T2*-corrected PDFF parametric maps were generated. PDFF values were recorded from regions of interest (ROIs) drawn on the maps in each of the nine Couinaud segments and three ROIs colocalized to the MRS voxel location. Regression analyses assessing agreement with MRS were performed to evaluate the accuracy of each MRI method, and Bland-Altman and intraclass correlation coefficient (ICC) analyses were performed to assess agreement between the MRI methods. RESULTS: MRI-M and MRI-C PDFF were accurate relative to the colocalized MRS reference standard, with regression intercepts of 0.63% and -0.07%, slopes of 0.998 and 0.975, and proportion-of-explained-variance values (R2 ) of 0.982 and 0.979, respectively. For individual Couinaud segments and for the whole liver averages, Bland-Altman biases between MRI-M and MRI-C were small (ranging from 0.04 to 1.11%) and ICCs were high (≥0.978). CONCLUSION: Both MRI-M and MRI-C accurately estimated hepatic PDFF in children, and high intermethod agreement was observed. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1641-1647.

In vivo triglyceride composition of abdominal adipose tissue measured by 1 H MRS at 3T.

PURPOSE: To investigate the regional variability of adipose tissue triglyceride composition in vivo using 1 H MRS, examining potential confounders and corrections for artifacts, to allow for adipose tissue spectrum estimation. MATERIALS AND METHODS: 1 H magnetic resonance (MR) stimulated echo acquisition mode (STEAM) spectra were acquired in vivo at 3T from 340 adult patients (mean age 48.9 years, range 21-79 years; 172 males, 168 females; mean body mass index [BMI] 34.0, range 22-49 kg/m2 ) with known or suspected nonalcoholic fatty liver disease (NAFLD) in deep (dSCAT), surface (sSCAT) subcutaneous adipose tissue, and visceral adipose tissue (VAT). Triglyceride composition was characterized by the number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). A subset of patients (dSCAT n = 80, sSCAT n = 55, VAT n = 194) had the acquisition repeated three times to examine the repeatability of ndb and nmidb estimation. RESULTS: Mean ndb and nmidb showed significant (P < 0.0001) differences between depots except for dSCAT and sSCAT nmidb (dSCAT ndb 2.797, nmidb 0.745; sSCAT ndb 2.826, nmidb 0.737; VAT ndb 2.723, nmidb 0.687). All ndb and nmidb estimates were highly repeatable (VAT ndb ICC = 0.888, nmidb ICC = 0.853; sSCAT: ndb ICC = 0.974, nmidb ICC = 0.964; dSCAT: ndb ICC = 0.959, nmidb ICC = 0.948). CONCLUSION: Adipose tissue composition can be estimated repeatably using 1 H MRS and different fat depots have different triglyceride compositions. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1455-1463.

Reproducibility of MR-based liver fat quantification across field strength: Same-day comparison between 1.5T and 3T in obese subjects.

PURPOSE: To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38-53 kg/m(2) ) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths. RESULTS: 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R(2) values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = -1.4 [-2.4, -0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [-0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R(2) = 0.98 (m = 1.1 [1.02, 1.16], b = -1.8 [-2.8, -1.1]) at 1.5T, and R(2) = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. CONCLUSION: This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods.