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.