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

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 8weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6weeks 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 6weeks, but significant fibrosis was observed only in mice fed MCD for 6weeks. 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±0.7min; MCD 6w, 12.1±1.6min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6weeks compared to the control group (control, 19.9±2.0min; MCD 4w, 46.7±8.7min; MCD 6w, 65.4±8.8min). 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.

journal_name

Magn Reson Imaging

authors

Yamada T,Obata A,Kashiwagi Y,Rokugawa T,Matsushima S,Hamada T,Watabe H,Abe K

doi

10.1016/j.mri.2016.03.009

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

724-729

issue

6

eissn

0730-725X

issn

1873-5894

pii

S0730-725X(16)00031-X

journal_volume

34

pub_type

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