The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: Comparison with simple steatosis mice

Purpose: To clarify the development of HCC, temporal change of steatosis and Gd-EOB-DTPA enhancement of non-alcoholic steatohepatitis (NASH) model mice by magnetic resonance imaging (MRI).

Materials and methods: All animal experiments were approved by the institution's Animal Research Committee. MRI was performed on six NASH and six simple steatosis (SS) model mice every 2weeks from the ages of 8weeks to 16weeks. The sequential changes in the number and size of the focal liver lesions detected on Gd-EOB-DTPA-enhanced MRI were evaluated. Additionally, the hepatic fat fraction (HFF), contrast-to-noise ratio (CNR) and relative enhancement (RE) were calculated at each time point. The temporal changes and correlations in these parameters were evaluated.

Results: All alive NASH model mice demonstrated focal liver lesions from week 10, at the latest. Number of the lesions increased with time, and all the lesion enlarged with time. All the lesions larger than 1mm were confirmed as hepatocellular carcinoma (HCC) pathologically. While the HFF remained constant in NASH model mice, HFF in SS model mice dramatically increased with time. CNR of the NASH model mice remained constant through the study period, while CNR in SS model mice decreased with time. Although no correlation was seen in NASH model mice, the HFF showed a negative correlation against CNR and RE in SS model mice.

Conclusion: Development of HCC was observed using Gd-EOB-DTPA-enhanced MRI only in NASH model mice. Degree of steatosis and hepatic enhancement by Gd-EOB-DTPA was both constant in NASH model mice, while steatosis increased and hepatic enhancement decreased with time in SS model mice.