Ability of dynamic gadoxetic acid-enhanced magnetic resonance imaging combined with water-specific T1 mapping to reflect inflammation in a rat model of early-stage nonalcoholic steatohepatitis.

Abstract

Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) has shown potential in reflecting the hepatic function alterations in nonalcoholic steatohepatitis (NASH). The purpose of this study was to evaluate whether Gd-EOB-DTPA combined with water-specific T1 (wT1) mapping can be used to detect liver inflammation in the early-stage of NASH in rats. In this study, 54 rats with methionine- and choline-deficient (MCD) diet-induced NASH and 10 normal control rats were examined. A multiecho variable flip angle gradient echo (VFA-GRE) sequence was performed and repeated 40 times after the injection of Gd-EOB-DTPA. The wT1 of the liver and the reduction rate of wT1 (rrT1) were calculated. All rats were histologically evaluated and grouped according to the NASH Clinical Research Network scoring system. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of Gd-EOB-DTPA transport genes. Analysis of variance and least significant difference tests were used for multiple comparisons of quantitative results between all groups. Multiple regression analysis was applied to identify variables associated with precontrast wT1 (wT1pre), and receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance. The rats were grouped according to inflammatory stage (G0 =4, G1 =15, G2 =12, G3 =23) and fibrosis stage (F0 =26, F1 =19, F2 =9). After the infusion of Gd-EOB-DTPA, the rrT1 showed significant differences between the control and NASH groups (P<0.05) but no difference between the different inflammation and fibrosis groups at any time points. The areas under curve (AUCs) of rrT1 at 10, 20, and 30 minutes were only 0.53, 0.58, and 0.61, respectively, for differentiating between low inflammation grade (G0 + G1) and high inflammation grade (G2 + G3). The MRI findings were verified by qRT-PCR examination, in which the Gd-EOB-DTPA transporter expressions showed no significant differences between any inflammation groups. The wT1 mapping quantitative method combined with Gd-EOB-DTPA was not capable of discerning the inflammation grade in a rat model of early-stage NASH.