Hepatic R2*is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease

• Type of Material: Article
• Authors: Mustafa R. Bashir, Duke University; Tanya Wolfson, University of California San Diego; Anthony C. Gamst, University of California San Diego; Kathryn J. Fowler, Washington University; Michael Ohliger, University of California San Francisco; Shetal N. Shah, Cleveland Clinic; Adina Alazraki, Emory University; Andrew T. Trout, Cincinnati Childrens Hospital Medical Center; Cynthia Behling, University of California San Diego; Daniela S. Allende, Cleveland Clinic; Rohit Loomba, University of California San Diego; Arun Sanyal, Virginia Commonwealth University; Jeffrey Schwimmer, University of California San Diego; Joel E. Lavine, Columbia College of Physicians and Surgeons; Wei Shen, Columbia University; James Tonascia, Johns Hopkins University; Mark L. Van Natta, Johns Hopkins University; Adrija Mamidipalli, University of California San Diego; Jonathan Hooker, University of California San Diego; Kris V. Kowdley, Swedish Medical Center; Michael S. Middleton, University of California San Diego; Claude B. Sirlin, University of California San Diego
• Language: English
• Date: 2019-05-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 International Society for Magnetic Resonance in Medicine
• Final Published Version (URL): http://dx.doi.org/10.1002/jmri.26312
• Title of Journal or Parent Work: Journal of Magnetic Resonance Imaging
• Volume: 49
• Issue: 5
• Start Page: 1456
• End Page: 1466
• Grant/Funding Information: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713).; Additional support is received from the National Center for Advancing Translational Sciences (NCATS) (grants UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000454).
• Keywords: NAFLD; Opposed phase; Steatosis; Life Sciences & Biomedicine; Radiology, Nuclear Medicine & Medical Imaging; nonalcoholic fatty liver disease; R2*; hepatic steatosis; Children; Quantification; Science & Technology; NASH; PDFF; proton density fat fraction; Vitamin E; nonalcoholic steatohepatitis
• Research Categories: Biology, Biostatistics; Health Sciences, Pathology; Health Sciences, Radiology

Abstract

Background: The 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. Purpose: To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). Study Type: Retrospective analysis of prospectively acquired data. Population: Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials. Field Strength: 1.5T and 3T; chemical-shift encoded multiecho gradient echo. Assessment: Correlation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*. Statistical Tests: Pearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method. Results: Hepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P < 0.0001) and at 3T (r = 0.586, P < 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength. Data Conclusion: Hepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only. Level of Evidence: 4. Technical Efficacy: Stage 2. J. Magn. Reson. Imaging 2019;49:1456–1466.