Model-based analysis of Gd-BOPTA-induced MR signal intensity changes in cirrhotic rat livers

Abstract

Objective: To quantify the hepatic transport of the hepatobiliary contrast agent gadobenate dimeglumine (Gd-BOPTA) in rats with biliary cirrhosis of various severity degrees from magnetic resonance (MR) signal intensities using a population pharmacokinetic approach.

Materials and methods: MR signal intensity was recorded during the Gd-BOPTA perfusion of normal and cirrhotic isolated rat livers. Similar experiments were conducted with Gd-labeled Gd-BOPTA to quantify Gd-BOPTA content in liver, bile, and perfusate. All experimental data were analyzed together according to a population pharmacokinetic approach.

Results: A 6-compartment model developed from the radioactivity data adequately fit all MRI data when 4 image parameters were added to describe the relationship between the amount of contrast agent and the signal intensity. The model showed that entry of Gd-BOPTA into hepatocytes was decreased in cirrhotic livers when compared to normal livers.

Conclusions: Although the MR signal intensity is similar in normal and cirrhotic livers, the population pharmacokinetic approach developed in this study shows a decreased entry of Gd-BOPTA into cirrhotic hepatocytes.