MRI versus histological methods for time course monitoring of steatosis amount in a murine model of NAFLD.
OBJECTIVE
Hepatic steatosis is an increasingly frequent disease with potentially severe complications. A simple quantification method is required for pretherapeutic studies to allow steatosis monitoring. This study aimed at evaluating steatosis quantification via a standard 1.5T MRI machine in a murine model.


METHODS
Eleven groups of two rats received a choline methionine deficient diet. MRI was performed at days 0, 2, 4, 5, 6, 7 and 8, and weeks 2, 3, 4 and 5. A phased array surface coil system was used to acquire a GE T1 in- and out-of-phase multi-echo sequence, with neither cardiac nor respiratory synchronization. Steatosis was calculated with the 3-echoes method. Histological quantifications were performed both by optical analysis (percentage of fatty hepatocytes) and by automated measurement of the area of steatosis (AOS). The reference was total intrahepatic triglycerides (TIT). Protocol was approved by the ethic committee.


RESULTS
Steatosis without inflammation, increasing with diet duration, was obtained. MRI provided better agreement (intraclass correlation coefficient) with TIT (0.889, p<0.001) than did AOS (0.629, p=0.001) or optical analysis (0.280, p=0.098). MRI permitted closer monitoring of TIT over time than did AOS or optical analysis. By multivariate analysis, MRI was an independent predictor of TIT on first step and ALT on second step. A model combining these 2 variables provided excellent agreement with TIT (0.953, p<0.001) and permitted excellent monitoring of steatosis over time.


CONCLUSIONS
MRI is reliable, easy, fast and superior to histological techniques for the assessment of hepatic steatosis in a murine model.
Department of Radiology, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: lm.leiber@gmail.com.
L-M
LM
Leiber
Department of Hepatology, Laboratory HIFIH, UPRES 3859, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: JeBoursier@chu-angers.fr.
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J
Boursier
Department of Pathology, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: SoMichalakProvost@chu-angers.fr.
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S
Michalak
LISA - laboratoire d'ingénierie des systèmes automatisés, LUNAM université, 62, avenue Notre-Dame-du-Lac, 49000 Angers, France. Electronic address: vincent.roullier@gmail.com.
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V
Roullier
Laboratory HIFIH, UPRES 3859, LUNAM université, 4, rue Larrey, 49000 Angers, France. Electronic address: lionel.fizanne@univ-angers.fr.
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L
Fizanne
Laboratory HIFIH, UPRES 3859, LUNAM université, 4, rue Larrey, 49000 Angers, France. Electronic address: julien.chaigneau@univ-angers.fr.
J
J
Chaigneau
Laboratory HIFIH, UPRES 3859, LUNAM université, 4, rue Larrey, 49000 Angers, France. Electronic address: Jerome.Roux@univ-angers.fr.
J
J
Roux
Department of Biology, Laboratory HIFIH, UPRES 3859, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: VaMoal@chu-angers.fr.
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V
Moal
Inserm, UMR-S 872, centre de recherches des Cordeliers, rue de l'École-de-Médecine, 75006 Paris, France. Electronic address: melissa.flamment@parisdescartes.fr.
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M
Flamment
Department of Radiology, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: paul.bazeries@gmail.com.
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P
Bazeries
Department of Endocrinology, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: PHDucluzeau@chu-angers.fr.
P-H
PH
Ducluzeau
Department of Hepatology, Laboratory HIFIH, UPRES 3859, LUNAM université, CHU Angers, 4, rue Larrey, 49000 Angers, France. Electronic address: chaube@chu-angers.fr.
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C
Aube
D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D002796:Choline Deficiency; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008715:Methionine / Q000172:deficiency; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D014280:Triglycerides / Q000032:analysis
D014280:Triglycerides; D008715:Methionine
Animal model; Fatty liver; Histology; Magnetic resonance imaging; Quantification