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

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• 作者：Tomomi Yamada^a ; Atsushi Obata^a ; Yuto Kashiwagi^a ; Takemi Rokugawa^a ; Shuuichi Matsushima^b ; Tadateru Hamada^c ; Hiroshi Watabe^d ; Kohji Abe^a ; ^{kohji.abe@shionogi.co.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dynamic contrast-enhanced-magnetic resonance imaging ; Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid ; Nonalcoholic steatohepatitis ; Mouse ; Methionine-choline-deficient (MCD) diet
• 刊名：Magnetic Resonance Imaging
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：34
• 期：6
• 页码：724-729
• 全文大小：1100 K

文摘

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.