Abstract
Previous studies have shown low-intensity ultrasound used with intravascular microbubbles (uB) disrupts tumor neovasculature. This study aims to evaluate changes in vascular perfusion following antivascular ultrasound (AVUS) therapy in a translational rat model of hepatocellular carcinoma (HCC). HCC was induced in 6 Wistar rats via diethylnitrosamine (DEN) ingested in drinking water for 12 weeks. Rats received AVUS therapy at low and high doses. The low dose group (n = 3) was treated at 1 W/cm2 for 1 min with 0.2 mL perflutren lipid microspheres (microbubbles, uB) injected IV. The high dose group (n = 3) was treated at 2 W/cm2 for 2 min with 0.7 mL IV uB. Perfusion was assessed by nonlinear contrast (NLC) and power Doppler (PD) ultrasound imaging before and after therapy. From each imaging mode, peak enhancement (PE) and perfusion index (PI) were measured. Histologic analysis of H&E and trichrome sections was performed after natural death or euthanasia. In the high-dose group, perfusional measures of PE (PD) decreased by 32.1% on average, and PI decreased 29.3% following AVUS therapy. NLC showed similar decreases: reduction in PE by 42.9% and PI by 44.8%. Histopathologic correlation showed hemorrhagic necrosis covering 61.5% of tumors’ cross-sectional area. In contrast, the low-dose group showed only modest changes in perfusion, and on average showed slight increases in perfusional measures (PE and PI). PD showed an average increase of 4.5% and 6.9% in PE and PI, respectively. NLC similarly showed average increases of 1.3% and 54.9% in PE and PI, respectively. Histologically, the low dose group showed less severe hemorrhagic necrosis in only 19.5% tumor cross sectional area. High-dose AVUS showed decreased perfusion and increased hemorrhagic necrosis on US and histology, while changes were less severe with low-dose AVUS. These dose-dependent effects are now being investigated in our translational model of HCC to further refine this novel, image-guided interventional therapy.Tabled 1Max Dose uB%Hemorrhage on Tumor Cross-Sections (SEM)PE (PD) Decrease Avg (%) (SEM)PI (PD) Decrease Avg (%) (SEM)PE (NLC) Decrease Avg (%) (SEM)PI (NLC) Decrease Avg (%) (SEM)High-dose group0.7mL61.5 (10.6)32.1 (15.2)29.3 (17.0)42.9 (18.2)44.8 (14.4)Low-dose group0.3mL19.5 (9.6)-4.5 (6.7)-6.9 (13.7)-1.3 (13.0)-54.9 (21.1) Open table in a new tab
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