title: Accuracy and the effect of possible subject-based confounders of magnitude-based MRI for estimating hepatic proton density fat fraction in adults, using MR spectroscopy as reference.
abstract: OBJECTIVE
  To determine the accuracy and the effect of possible subject-based confounders of magnitude-based magnetic resonance imaging (MRI) for estimating hepatic proton density fat fraction (PDFF) for different numbers of echoes in adults with known or suspected nonalcoholic fatty liver disease, using MR spectroscopy (MRS) as a reference.
  
  
  METHODS
  In this retrospective analysis of 506 adults, hepatic PDFF was estimated by unenhanced 3.0T MRI, using right-lobe MRS as reference. Regions of interest placed on source images and on six-echo parametric PDFF maps were colocalized to MRS voxel location. Accuracy using different numbers of echoes was assessed by regression and Bland-Altman analysis; slope, intercept, average bias, and R2 were calculated. The effect of age, sex, and body mass index (BMI) on hepatic PDFF accuracy was investigated using multivariate linear regression analyses.
  
  
  RESULTS
  MRI closely agreed with MRS for all tested methods. For three- to six-echo methods, slope, regression intercept, average bias, and R2 were 1.01-0.99, 0.11-0.62%, 0.24-0.56%, and 0.981-0.982, respectively. Slope was closest to unity for the five-echo method. The two-echo method was least accurate, underestimating PDFF by an average of 2.93%, compared to an average of 0.23-0.69% for the other methods. Statistically significant but clinically nonmeaningful effects on PDFF error were found for subject BMI (P range: 0.0016 to 0.0783), male sex (P range: 0.015 to 0.037), and no statistically significant effect was found for subject age (P range: 0.18-0.24).
  
  
  CONCLUSIONS
  Hepatic magnitude-based MRI PDFF estimates using three, four, five, and six echoes, and six-echo parametric maps are accurate compared to reference MRS values, and that accuracy is not meaningfully confounded by age, sex, or BMI.
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Elhamy R
authors.initials: ER
authors.lastname: Heba
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Ajinkya
authors.initials: A
authors.lastname: Desai
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Zand
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputing Center (SDSC), University of California, San Diego, San Diego, California, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Wolfson
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Schlein
authors.affiliation: Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputing Center (SDSC), University of California, San Diego, San Diego, California, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gamst
authors.affiliation: Department of Medicine (Division of Gastroenterology and Hepatology), University of California, San Diego, San Diego, California, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Claude B
authors.initials: CB
authors.lastname: Sirlin
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, San Diego, California, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Middleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055815:Young Adult
keywords: MRS; NAFLD; magnitude-based MRI; steatosis