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

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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.

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Document Type: Research Article

Affiliations: 1: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea 2: Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea 3: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea 4: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea. [email protected]

Publication date: October 1, 2015

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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