| Background and objective: The ability to propagate, focus and direct with focused ultrasound (FU) allows focuses an extracorporeal source of ultrasound to a target tissue. Heating effect and cavitation are 2 main mechanisms, by which ultrasound treatment several disease. The ultrasound energy routes to a tightly focused target tissue, which produce local temperature above 56℃very rapidly(in less than 3 second)leads to instantaneous tissue coagulative necrosis. This is the basis of ultrasound ablation for tumors with single procedure, which be defined as HIFU ablation.Hyperthermia treatments rely on cells being held at temperatures of 43–50℃or times up to an hour. This leads to an inability for the cell to divide.For focused ultrasound hyperthermia usually accompanied by chemo- or radiotherapy, which to enhance the sensitization. The main mechanism of above mentioned ultrasound therapeutic applications is tissue heating. The"Perfusion-mediated tissue cooling"effect affect therapeutic efficiency. So, methods such as TAE or TACE, that reduce the blood supply to the target tumors are used to improve therapeutic efficacy.Except for heating effect, focused ultrasound has cavitations and mechanical effect, categorized as non-heating effect. By adjusting focused ultrasound parameter, achieved different effect. Our early research confirmed thrombose in femoral artery of rabbit by low-frequency FU (0.4MHz), but the damage of tissue surrounding blood vessel is recoverable lesion instead of coagulation necrosis, that indicate the non-heating effect of FU is also very important.The mechanism of occlude vessel is supposed that the non-heating effect of FU cause vessel contract and damage vessel endothelial cell leading to thrombogenesis. Therefore, a hypothesis was presented: low-frequency focused ultrasound can be a new non-invasive vessel occlusion method for tumor or vascular disease. Tumor nutrition vessel is mostly made of normal vessel branch and micrangium extended into tumor. Tumor cell even feed by collateral circulation when normal vessels around tumor were occluded alone. While to occlude micrangium extended into tumor, it can obtain completely interruption of blood supply for tumor. The characteristic of tumor vessel is different with normal vessel, which usually is made of endothelial cell without integrated smooth muscle. The mechanisms of vessel occlusion and whether that could retard the quickly growth of tumor, previous experiment have not been well established. This is an area requiring further investigation. Therefore, this study was designed to explore the effect of previous experimental US paramete(r0.4MHz)on blood vessel of rabbits muscle tumor and growth of tumor, aimed to assess whether ultrasound with frequency 0.4MHz is able to embolism tumor vessels and retards tumor growth. This will be a new non-invasive embolism tumor vessel and therapy modality or adjunctive therapy method for tumors.Methods: The VX2 carcinoma was established in the rabbit vastus lateralis with tumor tissue implanted, 33 bearing cancer rabbits were divided randomly into group A and B. 15 rabbits in A group was observed by ultrasonography and color Doppler flow imaging for characteristics of tumors, including shape,echo and blood supply of tumors and tumor volume and growth rate were calculated; 18 rabbits in B group, the bionomics of tumor model, such as tumor histology pathology and tumor metastasis were observed by gross anatomy and pathology examine.A total of 80 rabbits that were implanted about 2 weeks and bearing tumor were divided randomly into A,B,C and D group at a 1:1:1:1 ratio, FU sonication with focal intensity 0W/cm2,1194W/cm2,1592W/cm2,1990W/cm2 were performed. The histology change, also the ultra-structural change of rabbit muscle tumor at 3rd,7th day after FU sonication was studied. The rabbit muscle tumor volume and echo change were follow-up by ultrasonography; The rabbit muscle tumor bloodstream and dyeing were follow-up by CDFI and DSA at the 3rd,7th day after FU sonication.Results: The successful rate of 100% for tumor formed. Infection rate and death rate of tumor bearing rabbits are 0%, the carcinoma was no spontaneous regression of tumor was observed until rabbit natural death. Natural live time of VX2 muscle tumor model is (45±5) days. After 25 days, only lung metastasis was occurred, and no other organ metastasis focuses was found in this study.After FU (0.4MHZ), (1) when focal intensity of 1194W/cm2, tumor tissue has not change, tumor still grows rapidly, tumor blood supply is abundant. (2) when focal intensity of 1592W/cm2, at the 7th day after FU, part of tumor vascular endothelial cell swelling,erythrocyte aggregation in the blood vessel, tumor cell hydropic degeneration, tumor vessel decreasing and tumor growth shutdown slightly.(3) when focal intensity of 1990W/cm2, at the 3rd day, earlily stage thrombogenesis in some of tumor vessel, vascular endothelial cell shedding, tumor cell slight pyknosis. Tumor growth shutdown and tumor blood supply decreasing; at the 7th day, vascular endothelial cells dissolved, thrombogenesis in most of tumor vessel and completely obstructed tumor vessel, tumor cell karyorrhexis and karyolysis, appear as inconstruction lamellar red dye. Tumor growth shutdown obviously, tumor has little or no blood supply, no dyeing.Conclusions: The methods of establishing rabbit VX2 muscle tumor model is feasibility, The form tumor rate is high, infection and death rate are very low and live time of VX2 muscle tumor model is long, the implanted spot is superficial and easy to find tumor, tumor metastasis to lung only and tumor metastasis occurred later.So this tumor model is a relative ideal big animal malignant tumor model, which can be used to study the response to pulmonary metastasis with tumor region therapy,earlier stage tumor therapy and local tumor therapy. FU with 0.4MHz, the effect to tumor vessel is different base on different sound energy density; the focal intensity of 1990W/cm2, which can make tumor vessel embolism, tumor cell necrosis and tumor growth is obviously inhibited.
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