Multimodal Sonographic Assessment of Hepatocellular Carcinoma Response to Antivascular Therapy

Low-intensity ultrasound (US) with microbubbles (uB) has been shown to disrupt the tumor neovasculature. The purpose of this study was to investigate the treatment effects of antivascular ultrasound (AVUS) in a realistic autochthonous rat model of hepatocellular carcinoma (HCC) using multimodal contrast-enhanced ultrasound imaging. HCC was induced in rats via by ingestion of diethylnitrosamine and treated with low intensity ultrasound in the presence of microbubbles. Tumor perfusion was assessed by linear-contrast, nonlinear-contrast and power Doppler ultrasound imaging before and after AVUS treatment. The tumor area perfused and hemodynamic characteristics were measured from time-dilution curves of the contrast agent. Histology of the treated samples was assessed for hemorrhage and necrosis induced by vascular disruption. All modes of contrast-enhanced imaging showed reduction in tumor vascularity following AVUS treatment. Perfusion area peak-enhancement and perfusion index were attenuated by 17% to 54% and the reduction in each measure was significant (p<; 0.05). Sham treatment involving no ultrasound and contrast agent did not show change in perfusion following AVUS treatment. Histology showed extensive necrosis and hemorrhage following AVUS treatment. In conclusion, different modes of contrast-enhanced ultrasound imaging along with histology confirmed disruption of tumor perfusion induced by AVUS therapy. This validation in a translational model sets the stage for future evaluation of AVUS to treat HCC in human subject.