title: Measuring liver triglyceride content in mice: non-invasive magnetic resonance methods as an alternative to histopathology.
abstract: OBJECTIVE
  Quantitative assessment of liver fat is highly relevant to preclinical liver research and should ideally be performed non-invasively. This study aimed to compare three non-invasive Magnetic Resonance (MR) and two histopathological methods against the reference standard of biochemically determined liver triglyceride content (LTC).
  
  
  METHODS
  A total of 50 mice [21 C57Bl/6OlaHsd mice (C57Bl/6), nine low-density lipoprotein (LDL) receptor knock-out -/- (LDL -/-) mice and 20 C57BL/6 mice] received either a high-fat, high-fat-high-cholesterol or control diet, respectively. Mice were examined 4, 8 or 12 weeks into the diet using MR [(1)H-MR Spectroscopy, Proton Density Fat Fraction (PDFF), mDixon] and histopathological methods (visual scoring or digital image analysis (DIA) of Oil-Red-O (ORO) stained liver sections). Correlations [Pearson's coefficient (r)] were studied with respect to LTC.
  
  
  RESULTS
  Microvesicular steatosis was seen in 42/50 mice. (1)H-MRS values showed normal to moderately elevated liver fat content. Visual scoring and DIA of ORO-sections correlated moderately with LTC at r = 0.59 and r = 0.49 (P < 0.001), respectively. (1)H-MRS, PDFF and mDixon correlated significantly better, at r = 0.74, r = 0.75 and r = 0.82, respectively.
  
  
  CONCLUSIONS
  Non-invasively determined MR measures of normal to moderately elevated liver fat in mice had a higher correlation with LTC than invasive histopathological measures. Where available, MR is the preferred method for fat quantification.
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands, j.h.runge@amc.uva.nl.
authors.forename: Jurgen H
authors.initials: JH
authors.lastname: Runge
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Bakker
authors.forename: Ingrid C
authors.initials: IC
authors.lastname: Gaemers
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.forename: Theo B M
authors.initials: TB
authors.lastname: Hakvoort
authors.forename: Roelof
authors.initials: R
authors.lastname: Ottenhoff
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.forename: Jaap
authors.initials: J
authors.lastname: Stoker
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D005234:Fatty Liver; D007091:Image Processing, Computer-Assisted; D008027:Light; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001391:Azo Compounds; D011973:Receptors, LDL; D014280:Triglycerides; C011049:oil red O