Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging

Rationale and Objectives: To investigate the potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for the differential diagnosis of nonalcoholic steatohepatitis (NASH) and fatty liver (FL). Methods: Twenty-one male rats were divided into 3 groups. Seven rats in the NASH group were fed a choline-deficient diet for 10 weeks, and the 7 rats in the FL group were fed a standard diet also containing 1% (wt/wt) orotic acid for 4 weeks. As a control, 7 rats were fed a standard diet. After the feeding period, all rats were subjected to contrast-enhanced dynamic and delayed MRI with a 2D-FLASH technique. Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected into the tail vein at 24-hour intervals. Signal intensities of the liver were measured for each MR image and the relative enhancement (RE) was calculated. In addition, the time of maximum RE (T-max) and the half-life of RE (T-1/2) in liver were compared. After MRI, the liver was histologically analyzed to evaluate steatosis, hepatitis, and fibrosis. Results: Diffuse macrovesicular steatosis and severe fibrosis were observed in the NASH group, whereas diffuse microvesicular steatosis and rare fibrosis were observed in the FL group. Immediately after the Gd-DTPA injection, the RE in the liver of each group temporarily increased, and thereafter, rapid RE reduction was observed. However, a continuous increase and subsequent slow reduction of RE were induced after the Gd-EOB-DTPA injection. Although there was no difference between the T-max and T-1/2 of each group after the Gd-DTPA injection, T-max and T-1/2 of the NASH group were significantly prolonged in comparison with FL and control groups after the Gd-EOB-DTPA injection (P < 0.01). Conclusions: It was possible to differentiate NASH and FL by evaluating the SI time course on Gd-EOB-DTPA enhanced MRI.