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

• Published in: Magnetic resonance imaging 2016-07, Vol.34 (6), p.724-729
• Main Authors: Yamada, Tomomi, Obata, Atsushi, Kashiwagi, Yuto, Rokugawa, Takemi, Matsushima, Shuuichi, Hamada, Tadateru, Watabe, Hiroshi, Abe, Kohji
• Format: Article
• Language: English
• Subjects: Animals; Contrast Media; Disease Models, Animal; Dynamic contrast-enhanced-magnetic resonance imaging; Gadolinium DTPA; Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid; Image Enhancement - methods; Inflammation - diagnostic imaging; Inflammation - etiology; Liver - diagnostic imaging; Liver - pathology; Magnetic Resonance Imaging - methods; Male; Methionine-choline-deficient (MCD) diet; Mice; Mice, Inbred C57BL; Mouse; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - diagnostic imaging; Non-alcoholic Fatty Liver Disease - pathology; Nonalcoholic steatohepatitis; Radiology
• ISSN: 0730-725X; 1873-5894
• DOI: 10.1016/j.mri.2016.03.009

Abstract 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 (Tmax ) and half-life of elimination RE (T1/2 ) 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 Tmax 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. T1/2 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 (Tmax and T1/2 ) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax , rho = 0.69, P = 0.0007; inflammation vs Tmax , rho = 0.66, P = 0.00155; steatosis vs T1/2 , rho = 0.77, P < 0.0001; inflammation vs T1/2 , 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.