title: Evaluation of Nonalcoholic Fatty Liver Disease in C57BL/6J Mice by Using MRI and Histopathologic Analyses.
abstract: 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.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Ryu
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Woori
authors.initials: W
authors.lastname: Jo
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Sungwoong
authors.initials: S
authors.lastname: Jang
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Hyo-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Dong-Cheul
authors.initials: DC
authors.lastname: Woo
authors.affiliation: Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Yu
authors.affiliation: 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. wcson@amc.seoul.kr.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001706:Biopsy; D002796:Choline Deficiency / Q000150:complications; D004195:Disease Models, Animal; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008715:Methionine / Q000172:deficiency; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000473:pathology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D008715:Methionine