Evaluation of Nonalcoholic Fatty Liver Disease in C57BL/6J Mice by Using MRI and Histopathologic Analyses

Nonalcoholic fatty liver disease (NAFLD) can lead to cirrhosis, hepatocellular carcinoma, and ultimately death. Magnetic resonance techniques are accurate, noninvasive methods for evaluating hepatic steatosis but, in animals, have not been fully validated against histologic findings. We sought to va...

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Bibliographic Details
Published in:Comparative medicine 2015-10, Vol.65 (5), p.409-415
Main Authors: Ryu, Jae-Eun, Jo, Woori, Choi, Hyun-Ji, Jang, Sungwoong, Lee, Hyo-Ju, Woo, Dong-Cheul, Kim, Jeong Kon, Kim, Kyung Won, Yu, Eun Sil, Son, Woo-Chan
Format: Article
Language:English
Subjects:
Animals
Area Under Curve
Biopsy
Choline Deficiency - complications
Disease Models, Animal
Liver - pathology
Magnetic Resonance Imaging
Methionine - deficiency
Mice, Inbred C57BL
Mouse Models
Non-alcoholic Fatty Liver Disease - etiology
Non-alcoholic Fatty Liver Disease - pathology
Predictive Value of Tests
Reproducibility of Results
ROC Curve
Severity of Illness Index
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Summary:Nonalcoholic fatty liver disease (NAFLD) can lead to cirrhosis, hepatocellular carcinoma, and ultimately death. Magnetic resonance techniques are accurate, noninvasive methods for evaluating hepatic steatosis but, in animals, have not been fully validated against histologic findings. We sought to validate the MRI fat-signal fraction (MRI-FSF) used for diagnosing NAFLD in human nonclinical trials by comparing MRI data with histopathologic findings in C57BL/6J mice (n = 24) fed normal chow (controls) or a methionine- and choline-deficient (MCD) diet to induce NAFLD. Axial T2-weighted fast spin-echo images were used to examine the entire liver. For histopathologic analyses, liver slides were evaluated for hepatic steatosis according to the NAFLD activity score. Pearson correlation coefficient and receiver operating characteristics analyses were performed. According to the fat-fraction signal, the mean percentage of liver fat in mice with induced NAFLD was 57%, which correlated with the histologically determined steatosis grade. The proton-density fat fraction effectively distinguished severe from mild hepatic steatosis, with an AUC of 0.92. Evaluation accuracy decreased when lobular inflammation and hepatocellular ballooning were considered. This study showed strong concurrence between MRI-FSF and histopathologic steatosis in a murine model of NAFLD. MRI-FSF had moderate sensitivity and specificity in this context. These results confirm that the MRI is a useful biomarker of hepatic steatosis in NAFLD in murine model.
ISSN:1532-0820