An Experimental Study On High Intensity Focused Ultrasound In The Treatment Of VX2 Rabbit Liver Tumors And Ablation Assisted With Sonovue

Part one Study on high intensity focused ultrasound in the treatment of VX2 rabbit liver tumors and the control of tumor metastasisObjectiveTo investigate the effectiveness of high intensity focused ultrasound(HIFU) in the treatment of liver tumors and the control of tumor metastasisMethodsSixteen New Zealand rabbits bearing VX2 liver tumors were irradiated with HIFU at an intensity Eight other tumor bearing rabbits served as controls. The treated rabbits were sacrificed at different periods after irradiation to observe the pathological changes. Eight of the treatment and the control group each were killed on the 14th day to study the growing condition of the primary tumors and the status of lung metastasis. ResultsTumor cells underwent coagulation necrosis immediately after irradiation with HIFU. Irreversible destruction was observed under electron microscope. The primary tumors in eight rabbits of the treatment group had been completely eradicated; while in the other two,one residual tumor was found beyond the target area in each rabbit. The size of the residual tumors was59.8 mm~3and 10.4 mm~3, while the average size of the primary tumors in the control group was 1571.1±350.7 mm~3.Lung metastasis took place in 2 rabbits of the treatment group,with 10 and 3 metastatic nodules respectively. Lung metastasis occured in all the control animals.The number of metastatic nodules was 54±30. The difference between these two groups was significant.ConclusionsHIFU should be effective in the treatment of liver tumors and the control of tumor metastasis.Part two Effect of HIFU ablation on microvessel density and vascular endothelial growth factor in rabbit hepatcocellular carcinoma modelsObjectiveTo study the effect of high intensity focused ultrasound ablation(HIFU)on microvessel density(MVD)and vascular endothelial growth factor(VEGF)in rabbit hepatcocellular carcinoma(HCC)models. MethodsThe VX2 tumor cells were planted in the hepatic left-central lobe on 30 rabbits.All animals were divided into two groups randomly: HIFU group(n=25)and control group(n=5).The MVD and the expression of VEGF in the hepatocellular carcinoma(HCC)was detected by immunohistochemical SABC methods in control group and 0, 1,3,7,16 d after the operation in HIFU group.ResultsThe MVD and the expression of VEGF in the HCC tissue after HIFU treatment in the HIFU group were decreased significantly as compared with those in the control group(P<0.01).However,there was no significant difference in MVD and the expression of VEGF in the HCC tissue after HIFU treatment in the HIFU group among the different time points(P>0.05).ConclusionHIFU treatment can effectively destroy the micovessel,repress the neovascularization and reduce the blood supply of the HCC.Part three Transmission Electron Microscopy of Rabbit VX2 Liver Tumors After High-Intensity Focused Ultrasound Ablation Assisted With SonovueObjectiveTo observe sequential changes on rabbit VX2 liver tumors after HIFU ablation under electron microscope.MethodsThe VX2 tumor cells were planted in the hepatic left-central lobe on 30 rabbits.All animals were divided into two groups randomly: Rabbit livers in group A underwent single HIFU ablation , while those in group B were given ultrasound contrast agent SonoVue 0. 2 ml/ kg before HIFU exposure. Five rabbit s of group A and B were sacrificed respectively on 0 h , 6 d and 14 d after HIFU ablation. The tissue samples , including targeted tissues and untargeted tissues , were observed under transmission electron microscope.ResultsElectron microscope showed most of cell organs in targeted areas of group A and B disappeared early after HIFU but the basic cell structure existed in group A.On 6 d after HIFU ablation in the two groups all the cells in targeted areas disrupted and fibra bands were detected in the rim of the targeted areas. In surrounding areas , cells swelling in group B was more severe than that in group A and more apoptosis bodies were found in group B.ConclusionUltrasound contrast agent can promote effects of HIFU ablation on destroying cell ultrastructure and enlarging the region of HIFU ablation , which provide experimental evidence for controlling HIFU effects.