Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience

Abstract

AbstractPigs are an important translational research model for biomedical imaging studies, and especially for modeling diseases of the liver. Dynamic contrast enhanced (DCE)-MRI is experimentally used to measure liver function in humans, but has never been characterized in pig liver. Here we performed DCE-MRI of pig liver following the delivery of two FDA approved hepato-specific MRI contrast agents, Gd-EOB-DTPA (Eovist) and Gd-BOPTA (Multihance), and the non-hepatospecific agent Magnevist, and optimized the anesthesia and animal handling protocol to acquire robust data. A single pig underwent 5 scanning sessions over six weeks, each time injected at clinical dosing either with Eovist (twice), Multihance (twice) or Magnevist (once). DCE-MRI was performed at 1.5T for 60 minutes. DCE-MRI showed rapid hepatic MRI signal enhancement following IV injection of Eovist or Multihance. Efflux of contrast agent from liver exhibited kinetics similar to that in humans, except for one hyperthermic animal where efflux was very fast. As expected, Magnevist was non-enhancing in the liver. The hepatic signal enhancement from Eovist matched that seen in humans and primates, while the hepatic signal enhancement from Multihance was different, similar to rodents and dogs, likely the result of differential hepatic organic anion transport polypeptides. This first experience with these agents in pigs provides valuable information on contrast agent dynamics in normal pig liver. Given the disparity in contrast agent uptake kinetics with humans for Multihance, Eovist should be used in porcine models for biomedical imaging. Proper animal health maintenance, especially temperature, seems essential for accurate and reproducible results.