Assessment of angiogenesis of hepatocellular carcinoma using dynamic contrast enhanced MR and histopathologic correlation in an experimental rat model

Abstract

The stepwise course of hepatocellular carcinomas (HCC) develop through a progressive pathway from a benign regenerative nodule to a dysplastic nodule (DN) to small HCC, and finally to the overt HCC. Differential diagnosis remains difficult especially in areas of DN or small well-differentiated HCC. Recently developed dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging is a noninvasive imaging technique that can be used to quantify perfusion changes in the liver. The aim of our study was to assess the perfusion parameters and angiogenesis of HCC using DCE MR and to correlate it with histopathologic findings in an experimental rat model. In this study, 20 rats were continuously infused with diethylnitrosamine (DEN) for tumor induction, with the use of mini-pumps. After 32 to 36 weeks of DEN treatment, the rats underwent MRI of the liver with a 3-T MR imaging system. Perfusion parametric maps and perfusion parameters such as, time to peak (TTP) and peak enhancement (PE) were obtained by using a commercially available software package (Nordic ICE; NordicNeuroLab, Bergen, Norway). The nodules were corresponded precisely to DCE MR images.A total of 13 nodules were found in 12 rats; 5 DNs were identified in 5 rats and 8 HCCs (3 Edmonson grade I, 2 Edmonson grade I-II, 3 Edmonson grade II) were found in 7 rats. There were no statistical differences in blood perfusion parameters (TTP and PE) between nodules and their surrounding hepatic parenchyma. There were no significant differences in mean value of TTP, in histogram peak height (HPH), or in width of TTP between DN and HCC. However, there were significant differences in mean values of between PE and HPH of PE between DN and HCC. Mean value and HPH of PE showed statistically significant correlation with tumor grade.In conclusion, there were significant differences in mean value and HPH of PE between DN and HCC. In addition, there were substantial negative correlations between tumor grades and perfusion parameters with mean value and HPH of PE in DN and well-differentiated HCC. DCE MR imaging can be used in the differential diagnosis and management of liver disease along the multistep process of heparocarcinogenesis.