TY - JOUR
T1 - Measuring liver triglyceride content in mice: non-invasive magnetic resonance methods as an alternative to histopathology
AU - Runge, Jurgen H.
AU - Bakker, Pieter J.
AU - Gaemers, Ingrid C.
AU - Verheij, Joanne
AU - Hakvoort, Theo B. M.
AU - Ottenhoff, Roelof
AU - Nederveen, Aart J.
AU - Stoker, Jaap
PY - 2014
Y1 - 2014
N2 - 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). 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. 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. 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
AB - 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). 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. 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. 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
U2 - https://doi.org/10.1007/s10334-013-0414-3
DO - https://doi.org/10.1007/s10334-013-0414-3
M3 - Article
C2 - 24178986
SN - 0968-5243
VL - 27
SP - 317
EP - 327
JO - Magma (New York, N.Y.)
JF - Magma (New York, N.Y.)
IS - 4
ER -