Evaluation of hepatic function using dynamic contrast-enhanced magnetic resonance imaging in melanocortin 4 receptor-deficient mice as a model of nonalcoholic steatohepatitis

• Published in: Magnetic resonance imaging 2019-04, Vol.57, p.210-217
• Main Authors: Yamada, Tomomi, Kashiwagi, Yuto, Rokugawa, Takemi, Kato, Hideaki, Konishi, Haruyo, Hamada, Tadateru, Nagai, Ryohei, Masago, Yusaku, Itoh, Michiko, Suganami, Takayoshi, Ogawa, Yoshihiro, Abe, Kohji
• Format: Article
• Language: English
• Subjects: Dynamic contrast-enhanced-MRI; Gd-EOB-DTPA; High-fat diet; Melanocortin 4 receptor-deficient mice; NASH
• ISSN: 0730-725X; 1873-5894
• DOI: 10.1016/j.mri.2018.11.013

Melanocortin 4 receptor-deficient (MC4R-KO) mice fed a high-fat diet (HFD) develop liver pathology similar to human nonalcoholic steatohepatitis (NASH). However, although liver histology and blood biochemistry have been reported, hepatic function has not been evaluated. In the present study, we evaluated hepatic function in MC4R-KO mice fed an HFD using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium‑ethoxybenzyl‑diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). Wild type (WT) mice and MC4R-KO mice were fed a standard diet (SD) or an HFD for 20 weeks. The hepatic signal intensity was obtained from DCE-MRI images, and relative enhancement (RE), the time to maximum RE (Tmax), and the half-life of RE elimination (T1/2) were calculated. Histopathological analysis was then performed. Histological analysis with nonalcoholic fatty liver disease activity score (NAS) revealed that MC4R-KO mice fed an HFD achieved the NAS of 5. There was moderate fibrosis in MC4R-KO mice fed an HFD. DCE-MRI with Gd-EOB-DTPA showed that Tmax and T1/2 were significantly longer in MC4R-KO mice fed an HFD compared with wild type (WT) mice (Tmax, WT, 3.9 ± 0.4 min; MC4R-KO, 7.4 ± 1.5 min; T1/2, WT, 23.7 ± 1.9 min; MC4R-KO, 62.5 ± 18.5 min). Tmax and T1/2 were significantly correlated with histopathologic score (steatosis vs. Tmax, rho = 0.48, P = 0.04; steatosis vs. T1/2, rho = 0.50, P = 0.03; inflammation vs. Tmax, rho = 0.55, P = 0.02; inflammation vs. T1/2, rho = 0.61, P