title: Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers.
abstract: Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the proton density fat-fraction (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13 explanted human livers. We performed colocalized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117) and tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction, and histology. Intraobserver agreement, interobserver agreement, and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984, confidence interval 0.978-0.989) and strong correlation with histology (r=0.850, confidence interval 0.791-0.894) and triglyceride extraction (r=0.871, confidence interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all P<0.001).
  
  
  CONCLUSIONS
  MRI-PDFF is an accurate, precise, and reader-independent noninvasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.|Department of Radiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bannas
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.|Department of Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Kramer
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Diego
authors.initials: D
authors.lastname: Hernando
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Agni
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Cunningham
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Mandal
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Utaroh
authors.initials: U
authors.lastname: Motosugi
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Samir D
authors.initials: SD
authors.lastname: Sharma
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Munoz del Rio
authors.affiliation: Department of Surgery, University of Wisconsin-Madison, Madison, WI.
authors.forename: Luis
authors.initials: L
authors.lastname: Fernandez
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI.|Department of Medical Physics, University of Wisconsin-Madison, Madison, WI.|Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI.|Department of Medicine, University of Wisconsin-Madison, Madison, WI.|Department of Emergency Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Reeder
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology*; D014280:Triglycerides / Q000032:analysis
chemical_list: D014280:Triglycerides