Comparative Study Between Lower-Intensity Ultrasound Pre-Exposure With HIFU And Purely HIFU On The Treatment Of Rabbit VX2 Liver Tumors

BackgroundHigh-intensity focused ultrasound (HIFU), as a rapidly developing non-invasive therapy, could focuse a large amount of acoustic energy in a millimeter-size focal spot in tissues located deep inside the body, while sparing intervening and surrounding tissues from harmful exposure. As a noninvasive, effective, and feasible treatment for liver tumors, the use of HIFU has evolved rapidly In recent years. However, there are still some problems in the clinical application of HIFU. HIFU leaded to a small focal reg ion and the low energy deposition in each exposure. ,but targeted volumes ,which was large in volume or deep in position or with high blood flow, usually required many HIFU exposures. Theoretically, this shortcoming could be overcome by elevating acoustic intensity or prolonging sonication duration. But both elevating acoustic intensity and prolonging sonication duration might increase the incidence of side effects. The ultrasound energy deposition mainly depended on the AET, i.e. "acoustic environment in tissue", including the tissue structure and its functional status. Therefore, the changing acoustic environment in tissue ( CAET )to make energy deposit more efficiently might improving HIFU efficiency. Lower-intensity ultrasound pre-exposure, which was a new way of CAET, could enhance the coagulated volume by increasing HIFU energy in the focal region. Based on selecting a properly low-intensity ultrasound (US) exposure as a medium to change the acoustic environment in the liver VX2 tumor tissue, this research was designed to evaluate the efficacy and safety of low-dose ultrasound with HIFU in ablation of rabbit VX2 liver tumors, and its influence on the growth of the residual tumors compared with purely HIFU therapy.Materlals and methods1 The HCC models were established by implanting VX2 tumor bits in the rabbit liver. Analyse the synergy of different low-intensity ultrasound pre-irradiation on high intensity focus ultrasound (HIFU) ablation of rabbit VX2 liver tumor.48 rabbits bearing VX2 tumors were randomly averagely divided into four groups. All liver tumors of rabbits underwent low-dose ultrasound pre-exposure with HIFU ablation, the different was the sound power of the low-intensity US, group A was 0 W, group B was 60 W, group C was 80W and group D was 100 W. Energy efficiency factor(EEF) was calculated after HIFU treatment. 2 Compare low-intensity US pre-exposure with HIFU with purely HIFU in the efficiency of treating rabbit VX2 liver tumors.67 rabbits bearing VX2 tumors were divided randomly into three groups. Group A was 27, received low-intensity US pre-exposure with HIFU; group B was 25, received purely HIFU exposure, group C was 15, received sham HIFU exposure. The exposure time of HIFU, the volume of BFR and the values of EEF between the enhancing therapy group and the purely HIFU therapy group were compared. TGR, survival time and the pulmonary metastasis were compared during the three groups.3 Compare low-dose ultrasound pre-exposure with HIFU with purely HIFU in the safety of treating rabbit VX2 liver tumors.45 rabbits bearing VX2 tumors were divided randomly into three groups. Group A received low-intensity US exposure before HIFU exposure; group B only received HIFU exposure; group C received sham HIFU exposure.The adverse reactions of HIFU treatment, including tissues damage on sound path (skin , abdominal wall and the liver membrane), organs damage nearby liver and liver bleeding, were compared between the enhancing therapy group and the purely HIFU therapy group.The effects on hepatic function and renal function 1 day before HIFU and 1 day, 4 days, 7 days after HIFU therapy were compared between the enhancing therapy group and the purely HIFU therapy group. The vascular expression of endothelial growth factor (VEGF) 1 day, 4 days and 7 days after HIFU therapy were compared during the three groups.Result1 With the increasing of the sound power of the low-intensity ultrasound, the value of EEF of HIFU was reduced, and power 100 of the low-intensity ultrasound produced the least value o f EEF ( P < 0.05 ).2 Compared with the purely HIFU therapy group, the low-intensity ultrasound changing the acoustic environment in tissue, could shorten the exposure time of HIFU ( P < 0.05 ), enlarge the volume of BFR ( P< 0.05) and decrease the value of EEF ( P < 0.05 ). Tumor growth was monitored with MRI 7 days after HIFU therapy. The TGR of sham-therapy group was obviously larger than the other therapy groups( P< 0.001) , and the TGR of enhancing HIFU group was the minimum ( P < 0.05 ).The pulmonary metastasis in the sham-therapy group significantly more than the other two therapy groups ( P < 0.001 ), but there had no significantly differences between the two therapy groups. The survival time of rabbits in the sham-therapy group was the shortest( P < 0.001) , and the survival time of enhancing HIFU group was slightly longer than that of purely HIFU group ( P < 0.05 ).3 Compared with the purely HIFU therapy group, the adverse reactions of HIFU treatment in enhancing group were less than those in purely HIFU group ( P< 0.05) . The blood biochemistry variation were temporary, it could recover within 7 days after HIFU in both therapy groups. The VEGF expression of residual tumor cells in enhancing group was slightly lower than that in purely HIFU group( P< 0.05) , and the sham-therapy group performed t he highest VEGF expression ( P < 0.001 ).Conclusion1 The sound power of the low-intensity ultrasound, when reached the threshold, could decrease the value of EEF. With the increasing of the sound power of the low-intensity ultrasound, the value of EEF of HIFU was reduced, but not blindly increase the power of the first irradiation to ensure the safety in clinical HIFU therapy.2 The low-intensity ultrasound was feasible and effective to enhance HIFU therapy; and long-term observation showed that enhancing therapy could promote the prognosis of rabbits bearing VX2 tumors and reduce the pulmonary metastasis.3 The low-intensity ultrasound was used to changing AET, which could reduce the adverse reactions of HIFU treatment and the VEGF expression of residual tumor cells . However, the mechanism of low-intensity US exposure enhancing HIFU therapy needed deeper research.