Hemocoagulase Combined with Microbubble-Enhanced Ultrasound Cavitation for Augmented Ablation of Microvasculature in Rabbit VX2 Liver Tumors

We investigated a new method for combining microbubble-enhanced ultrasound cavitation (MEUC) with hemocoagulase (HC) atrox. Our goal was to induce embolic effects in the vasculature and combine these with an anti-angiogenic treatment strategy. Fourteen days after being implanted with a single slice of the liver VX2 tumor, rabbits were randomly divided into five groups: (i) a control group injected intra-venously with saline using a micropump; (ii) a group given only an injection of HC; (iii) a group treated only with ultrasound cavitation; (iv) a group treated with MEUC; (v) a group treated with MEUC + HC. Contrast-enhanced ultrasound was performed before treatment and 1 h and 7 d post-treatment to measure tumor size, enhancement and necrosis range. QontraXt software was used to determine the time-intensity curve of tumor blood perfusion and microvascular changes. At 1 h and 7 d after treatment with MEUC + HC, the parameters of the time-intensity curve, which included peak value, regional blood volume, regional blood flow and area under the curve value and which were measured using contrast-enhanced ultrasound, were significantly lower than those of the other treatment groups. The MEUC + HC treatment group exhibited significant growth inhibition relative to the ultrasound cavitation only, HC and MEUC treatment groups. No damage was observed in the surrounding normal tissues. These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumors using a new method that combines MEUC and HC.