Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice

Objective: The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Materials and methods: Twenty male C57/BL6 mice aged 8 weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6 weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6 weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (T_max) and half-life of elimination RE (T_1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Results: Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6 weeks, but significant fibrosis was observed only in mice fed MCD for 6 weeks. Gd-EOB-DTPA-enhanced MRI showed that T_max was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0 ± 0.7 min; MCD 6w, 12.1 ± 1.6 min), although there was no alteration in the 2- and 4-week groups. T_1/2 was significantly prolonged in mice fed MCD for 4 and 6 weeks compared to the control group (control, 19.9 ± 2.0 min; MCD 4w, 46.7 ± 8.7 min; MCD 6w, 65.4 ± 8.8 min). The parameters of Gd-EOB-DTPA kinetics (T_max and T_1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs T_max, rho = 0.69, P = 0.0007; inflammation vs T_max, rho = 0.66, P = 0.00155; steatosis vs T_1/2, rho = 0.77, P < 0.0001; inflammation vs T_1/2, rho = 0.73, P = 0.0003). Conclusions: The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging.