Pharmacokinetic modeling of hepatospecific MRI contrast agent flux in large animal models by dynamic contrast-enhanced MRI.

Purpose: Evaluate the feasibility of using dogs and a pig as translational models for assessing hepatic flux of hepatospecific gadolinium-based contrast agents using dynamic contrast-enhanced MRI (DCE-MRI). Procedures: DCE-MRI was performed with hepatospecific agents, gadoxetate disodium (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA), and non-hepatospecific agents. Two validated pharmacokinetic models were applied: a single-input reference region model and a dual-input model using arterial and venous blood signals. Results: In dogs, hepatic enhancement rose rapidly and plateaued after Gd-EOB-DTPA administration, with minimal decline over an hour. In the pig, both hepatospecific agents showed a rapid rise, blunt peak, and gradual decline. The single-input model revealed significantly higher uptake rates for hepatospecific agents, confirming its sensitivity to hepatocyte uptake. The dual-input model effectively distinguished contrast agent dynamics in dogs and showed promise in the pig. Conclusions: In this feasibility study, canine Gd-EOB-DTPA pharmacokinetic values closely mirrored those observed in humans. These results establish baseline model parameters in a large-animal setting and support further, more comprehensive investigations into their translational potential for assessing hepatic function using DCE-MRI.