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

Mustafa R Bashir; Tanya Wolfson; Anthony C Gamst; Kathryn J Fowler; Michael Ohliger; Shetal N Shah; Adina Alazraki; Andrew T Trout; Cynthia Behling; Daniela S Allende; Rohit Loomba; Arun Sanyal; Jeffrey Schwimmer; Joel E Lavine; Wei Shen; James Tonascia; Mark L Van Natta; Adrija Mamidipalli; Jonathan Hooker; Kris V Kowdley; Michael S Middleton; Claude B Sirlin; NASH Clinical Research Network (NASH CRN)

doi:10.1002/jmri.26312

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

J Magn Reson Imaging. 2019 May;49(5):1456-1466. doi: 10.1002/jmri.26312. Epub 2018 Oct 14.

Authors

Mustafa R Bashir^{1

2

3}, Tanya Wolfson⁴, Anthony C Gamst⁴, Kathryn J Fowler⁵, Michael Ohliger⁶, Shetal N Shah⁷, Adina Alazraki⁸, Andrew T Trout⁹, Cynthia Behling¹⁰, Daniela S Allende¹¹, Rohit Loomba¹², Arun Sanyal¹³, Jeffrey Schwimmer¹⁴, Joel E Lavine¹⁵, Wei Shen¹⁶, James Tonascia¹⁷, Mark L Van Natta¹⁷, Adrija Mamidipalli¹⁸, Jonathan Hooker¹⁸, Kris V Kowdley¹⁹, Michael S Middleton¹⁸, Claude B Sirlin¹⁸; NASH Clinical Research Network (NASH CRN)¹

Affiliations

¹ Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA.
² Center for Advanced Magnetic Resonance Development (CAMRD), Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA.
³ Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
⁴ Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputing Center (SDSC), University of California-San Diego, San Diego, California, USA.
⁵ Department of Radiology, Washington University, St. Louis, Missouri, USA.
⁶ Departments of Radiology and Biomedical Engineering, University of California-San Francisco, San Francisco, California, USA.
⁷ Section of Abdominal Imaging and Nuclear Medicine Department, Imaging Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁸ Departments of Radiology and Pediatrics, Emory University School of Medicine/Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
⁹ Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁰ Department of Pathology, University of California-San Diego, La Jolla, California, USA.
¹¹ Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
¹² NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California-San Diego, La Jolla, California, USA.
¹³ Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁴ Department of Pediatrics, University of California-San Diego, San Diego, California, USA.
¹⁵ Department of Pediatrics, Columbia College of Physicians and Surgeons, New York, New York, USA.
¹⁶ Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Institute of Human Nutrition, Columbia University Medical Center, New York, New York, USA.
¹⁷ Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁸ Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
¹⁹ Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington, USA.

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.

Keywords: NAFLD; NASH; PDFF; R2*; hepatic steatosis; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; proton density fat fraction.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adipose Tissue / diagnostic imaging*
Adolescent
Adult
Aged
Child
Cross-Sectional Studies
Female
Humans
Iron / metabolism*
Liver / diagnostic imaging
Liver / metabolism
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Non-alcoholic Fatty Liver Disease / diagnostic imaging*
Non-alcoholic Fatty Liver Disease / metabolism*
Prospective Studies
Protons
Retrospective Studies
Young Adult

Substances

Protons
Iron

Abstract

Publication types

MeSH terms

Substances

Grants and funding