Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2 liver tumors: sequential findings with histopathology, immunohistochemistry, and enzyme histochemistry.

Abstract

We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry. Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed. The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05). Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.