Quantitative Pharmacokinetic Models Of Dynamic Contrast-enhanced Magnetic Resonance Imaging In Evaluating Microcirculation Of Hepatocellular Carcinoma

The purpose of this study is to establish and verify the pharmacokinetic models (a dual-input extended Tofts model and a dual-input exchange model) which is consisted with the dual blood supply physiopathological properties in advanced hepatocellular carcinoma (HCC) for providing an accurate and reliable assessment method to evaluate the therapeutic efficacy and diagnose HCC or differentiate it from other tumors.We register image data derived from dynamic contrast-enhanced magnetic resonance imaging in the HCC and hepatic metastases of colorectal cancer confirmed by pathology and clinical diagnosis using non-rigid registration technique to improve the fitting degree of time-concentration curves in blood supply vasculature and the accuracy of microvascular parameters in these liver tumors. We build dual-input two-compartment tracer kinetic models by fitting dual-input vascular input function of the hepatic artery and portal vein based on single-input two-compartment tracer kinetic models (extended Tofts model and exchange model), then measure and analyze the pharmacokinetic parameters (Ktrans、Fp、PS、Kep、Ve、Vp、HPI) in the advanced HCC by using dual-input extended Tofts model and exchange model; A paired Student’s T-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and correlation analysis was also applied to observe the correlations among all equivalent parameters for verifying microvascular parameters measured by dual-input two-compartment tracer kinetic model are consistent with the physiopathological properties in advanced HCC. We retrospectively measure and analyze the microvascular parameters to assess the microcirculation properties of hypervascular HCC and hypovascular hepatic metastases of colorectal cancer by using dual-input extended Tofts model and exchange model to diagnose or differentiate these two tumors for verifying the reliability of dual-input two-compartment pharmaco kinetic models.Our research indicates that both dual-input extended Tofts model and dual-input exchange model can be used in assessing the microvascular physiopathological properties before the pretreatment of advanced HCC by using three dimensional non-rigid registration. The dual-input extended Tofts model may be more stable in measuring the microvascular parameters; however, the dual-input exchange model may be more accuracy in measuring microvascular permeability. Parameters including Ktrans, Fp, Vp, and HPI derived from dual-input extended Tofts model and exchange model can be used to identify HCC and hepatic metastases of colorectal cancer. Among these parameters, Ktrans and HPI derived from exchange model have higher diagnostic value in differentiating HCC and hepatic metastases of colorectal cancer. Our study results verify that dual-input two-compartment pharmacokinetic models are consistent with the microvascular physiopathological properties in the advanced HCC, and provide a reasonable and reliable the therapeutic efficacy evaluation method for non-surgical operative HCC patient.