Comparison of three physiologically-based pharmacokinetic models for the prediction of contrast agent distribution measured by dynamic MR imaging

Purpose: To compare the performance of three physiologically-based pharmacokinetic (PBPK) models for predicting gadolinium. contrast agent concentration-time curves (Gd-CTCs) obtained in superior sagittal sinus (SSS), cerebral cortex, and psoas muscle. Materials and Methods: Three published whole-body PBPK models were modified to predict Gd-CTCs in normal-appearing tissue. The models differed in the number of organs modeled and total number of compartments, and were designated as the well-mixed, delay, and dispersion models. The suitability of the three models to predict Gd-CTC was studied using data from dynamic contrast-enhanced MR perfusion imaging obtained at 1.5T from 10 patients with glioblastoma multiforme and at 3.0T from five patients with liver metastases. Results: The dispersion model produced better fits than the delay model in the SSS (P < 0.0001) and cerebral cortex (P < 0.0001), and better fits than the well-mixed model in psoas muscle (P < 0.005). No model produced better fits than the dispersion model at any of the three locations. Conclusion: In this evaluation, the dispersion model was most robust for prediction of Gd-CTCs derived from dynamic contrast-enhanced (DCE)-MRI. This represents a preliminary step in the development of a PBPK model useful for predicting Gd-CTCs at a time resolution appropriate for dynamic MRI applications.