Model-Based Analysis of Gd-BOPTA-Induced MR Signal Intensity Changes in Cirrhotic Rat Livers

Abstract

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. 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. 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. 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.