| Objective:1. To observe and analyze the sonographic features and pathological changes in HIFU combined different dose of SonoVue and different HIFU power at definite treatment depth and therapeutic transducer. Explore the optimization HIFU power-SonoVue dosage of security and synergism.2. Use the optimization HIFU power-SonoVue dosage to discuss the mechanism of microbubble change acoustic environment, improve treatment efficiency in temperature rise under MRI monitoring HIFU treatmentMethods:1. JC HIFU tumor therapy system was used, the parameters of therapeutic transducer were: frequency 0.8 MHz, focal length 150 mm, diameter 150 mm. 46 Nanjiang Yellow Goat were adopted, use self-control, each goat irradiation of 2 to 3, each of 1 to 2 points; divided into HIFU combined with saline irradiation group (control group), and HIFU combined with microbubble contrast agent irradiation group (experimental group). Irradiation depth: 30 mm; irradiation time: 15 s; radiation power: 150,250,350 W; SonoVue dose: 0.01, 0.03, 0.05 ml / kg. Observe ultrasonogram at focus before, during and 0, 1, 2, 5, 10 min after HIFU ablation. Measure the areas of hyperecho at focus of different observation time, analysis the time of stationary hyper-echo. The next irradiation was at least 20 min after. These goats were sacrificed 7 days after treatment, and measurement of actual coagulation necrosis at largest surface area and volume of coagulation necrosis, necrotic foci were admitted to histopathological examination. Discuss the gray appear rate and necrosis appear rate of control group and experimental group at different radiation power and SonoVue dose, analysis the gray change regular during and after HIFU ablation at 0, 1, 2, 5, 10 min, and analysis the dependablity with coagulation necrosis at largest surface. Compare the necrosis volume of control group and experimental group at different radiation power and SonoVue dose. Find the combination of HIFU power and SonoVue dose of synergy and without movement of gray at focus.2. Magnetic resonance navigation of high intensity focused ultrasound therapy system was used. Treatment of frequency 0.8 MHz, the focal length of 150 mm, 150 mm in diameter. Six Nanjiang Yellow Goat, using self-control, divided into 2 groups: high-intensity focused ultrasound combined saline treatment group (the control group) and high-intensity focused ultrasound combined microbubble contrast agent treatment group (experimental group). The baseline temperature use goat anal irradiation temperature. Use optimized SonoVue concentration and radiation power in part 1, ablation goat's liver under MRI control, observing focal temperature changes before during and 10s after ablation. The next irradiation was performed at least 10 min after. These animals were sacrificed 7 days later, and measurement of coagulation necrosis at largest surface area and volume of coagulation necrosis. Lesions and the surrounding normal liver tissue were observed in pathology and comparative study of the experimental group and control group. Compare the changes of areas which temperature above 56℃of control group and experimental group, the areas of largest surface necrosis and the volume of necrosis respectively.Results:1. HIFU ablation goat liver combined SonoVue under ultrosonography control. Of visible hyperecho at the focus, 150 W, SonoVue dose 0.01, 0.03, 0.05 ml/kg experimental group and control group and 250 W control group and 0.01 ml/kg experimental group appear hyper echo at focus at 9~12 s during HIFU ablation. The target gray scale values and grey area gradually increased with the extension of irradiation time, target gray scale were observed at the beginning of ablation after 2~5s and gradually increasing with the extension of the irradiation time in which power is 250W, SonoVue dose of 0.03, 0.05ml/kg for the experimental group and power 350W of the control group and experimental group. At the end of irradiation, the target gray achieved maximum, and with the extension of time for observation, echo enhanced target area decreased gradually and achieved stable.2. After HIFU ablation instantly, we can see that power is 250 W, SonoVue doses: 0.05 ml / kg of the experimental group appeared to target gray movement toward transducer, a distance of: 3.0±1.5 mm. 350 W power for the control group and the SonoVue doses of 0.01,0.03,0.05 ml / kg experimental group, the distance of gray toward transducer are as follows: 5.4±2.6 mm,7.8±2.4 mm,11.6±2.8 mmå’Œ16.7±3.8 mm Each has compare significant difference (P <0.05). The distance of excursion became larger with the increase of SonoVue doses in 350 W.3. Chi-square test to the trend analysis of control group and experimental group at different HIFU power and SonoVue dose: the gray appear rate of experimental group exceed control group, the rate increased follow SonoVue dose, there was no significant difference between necrosis appear rate of experimental group and control group. The gray appear rate and necrosis rate of experimental group exceed control group, the rate increased follow SonoVue dose. There was no significant difference between experimental group and control group at gray appear rate and necrosis rate. During experiment , we found there was gray change but without necrosis appear of experimental group at different HIFU power, and necrosis appear without gray change at control group of 250, 350 W.4. The necrosis of 150 W control group and experimental group of SonoVue dose 0.01 ml/kg were respectively 1 and 2, so did not compare the dependability of areas of largest surface necrosis with hyperecho area. The hyperecho area went to stability at 1 min after ablation of 150 W, SonoVue dose 0.03, 0.05 ml/kg experimental group. The stability area of hyperecho is coincidence with areas of the largest surface necrosis. The hyperecho area went to stability at 2 min after ablation of 250 W, SonoVue dose 0.01 ml/kg experimental group. The hyperecho area went to stability at 5 min after ablation of 250 W, SonoVue dose 0.03, 0.05 ml/kg experimental group. The stability area of hyperecho is coincidence with areas of the largest surface necrosis. The hyperecho area went to stability at 5 min after ablation of 350 W, SonoVue dose 0.01 ml/kg experimental group and control group. The stability area of hyperecho is coincidence with areas of the largest surface necrosis. The hyperecho area did not went to stability at 10 min after ablation of 350 W, SonoVue dose 0.03, 0.05 ml/kg experimental group.5. The necrosis of 150 W control group and experimental group of SonoVue dose 0.01 ml/kg were less, so did not compare the volume of necrosis, the volume of necrosis of SonoVue 0.03, 0.05 ml/kg experimental group were 18.85±4.57 mm~3, 28.86±5.82 mm~3 , they has significant difference (P <0.05). The volume of necrosis of 250 W, SonoVue dose 0.01, 0.03, 0.05 ml/kg were respectively 86.68±13.38 mm~3, 138.68±21.55 mm~3, 186.68±24.24 mm~3 and 276.71±36.24 mm~3 , there has significant difference between experimental group and control group (P <0.05). The volume of necrosis of 350 W, SonoVue dose 0.01, 0.03, 0.05 ml/kg were respectively 257±13.38 mm~3,471.68±21.55 mm~3,689.68±24.24 mm~3åŠ878.71±36.24 mm~3 , there has significant difference between experimental group and control group (P <0.05). In the same HIFU power, the volume of necrosis of experimental group was larger than control group. In the experimental group, with the increasing concentration of SonoVue, the coagulation necrosis formed larger. the efficiency was more obvious6. After HIFU ablation, the experimental group and control group were formed coagulation necrosis, hepatocyte nuclear pyknosis, fragmentation and dissolution were found in the necrotic foci. The boundaries of coagulative necrosis and surrounding normal liver cells were clearly visible, and inflamm~atory cells and fibroblast proliferation were found in the junction.7. In MRI guide HIFU experiment, the temperature of the focal area increased gradually during HIFU ablation in control group and experimental group. The temperature increased sharply at the 2~5s of the beginning of irradiation of the experimental group, and then to the highest temperature 103.75±8.61℃, the temperature of the control group also achieve highest of 92.45±6.12℃after irradiation, and the two were statistically different (P <0.05). After irradiation, with the extension of time for observation, the target temperature gradually decreased.8. During irradiation, the area of temperature above 56℃region is gradually increasing, the size of the experimental group and control group achieved maximum at the cessation of radiation, the area respectively 37.52±4.83 mm~2 and 12.35±3.75 mm~2, the two were statistically different (P <0.05). The area of the largest coagulation necrosis region of the experimental group and the control group were 44.74±7.61 mm~2 and 16.32±4.61 mm~2 . There was a significant difference (P <0.05). The actual size of the necrosis are larger than the area of temperature above 56℃region whether in the experimental group or in the control group, the difference was significant (P <0.05).Conclusions:1. The time of gray scale appearance during HIFU ablation, gray scale appear ratio at focus after ablation and time of stabilization of hyperecho are effected by HIFU power and SonoVue dose.A. At low ablation power, SonoVue can rise hyperecho appear ratio and can conduce to ultrasound monitoring, but at higher ablation power, compare to the control group, there is no difference at rise hyperecho appear ratio of SonoVue.B. At a certain HIFU power and SonoVue dose, compare to the control group SonoVue can fast the appearance the hyperecho. But at high HIFU power, there is no difference between control group and experimental group.C. The time of stabilization of hyper echo after ablation extended follow the HIFU power and SonoVue dose, but at high HIFU power, high SonoVue dose, the hyperecho area need a long time to achieve stable. The area of stably hyperecho is coincident with necrosis areas of the largest surface. The area of stably hyperecho can be used to evaluation area of necrosis.2. The phenomenon that hyperecho move towards transducer are effected by ablation power and SonoVue dose. At high ablation power, the distance increased higher follow SonoVue dosage, and increased the risk of side effect.3. At low ablation power, lower SonoVue dose can not rise the volume of necrosis. But at high ablation power, SonoVue can rise the damage efficiency of HIFU ablation. At same ablation power, the efficiency and the volume of necrosis are more obvious follow higher SonoVue dose.4. The experimental group and the control group were observed white coagulation necrosis. The boundaries were visible between coagulation necrosis and normal liver tissue in light microscopy. The coagulation necrosis is undifferentiated between experimental group and control group.5. The experimental group of the power 250 W, SonoVue dose of 0.03 ml / kg was choose to the best compose of definite HIFU transducer and treatment depth, for it has significant synergy and without obvious hyperecho movement towards transducer.6. SonoVue can rise the temperature rise ratio at initial phase of HIFU ablation. Cause the tissue achieve high temperature at lower time. It indicate that SonoVue can increase the absorption of ultrasound of the tissue, accordingly accelerate energy deposit, and decurtate the time of necrosis formation, improved cure efficiency.7. Critical temperature can not judge whether there will be coagulation necrosis, and should be considered the temperature accumulation during HIFU ablation, and should use thermal dosage to demonstrate the area of necrosis.
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