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Objective: to explore different sound power-SonoVue dose combinations HIFU United microbubbles enhance the sonographic features and its pathological changes of goat liver damage and seek optimum sound power-SonoVue dose combination based on safety, efficiency conditions. Using optimum sound power-SonoVue dose combinations, real-time monitoring of the temperature rise of the HIFU combined with of SonoVue irradiation goat liver using MRI, explore microbubbles change the target acoustic environment, enhanced thermal damage, improve the treatment efficiency of the mechanism. Methods: 1, JC focused ultrasound tumor therapy system, the treatment of head and operating frequency of 0.8 MHz and a focal length of 150 mm, 150 mm in diameter. 46 Nanjiang yellow as the research object, the use of self-control, face each goat irradiation 2 to 3, 1 to 2 points of each face. Divided into the HIFU joint saline irradiation group (control group), and HIFU joint microbubble contrast agent SonoVue irradiation group (experimental group), their liver ultrasound monitoring HIFU sentinel irradiation. The irradiation depth: 30 mm; irradiation time: 15 s; irradiation sound power: 150, 250, 350 W; SonoVue dose of the experimental group were: 0.01,0.03,0.05 ml / kg and the control group with normal saline are the marginal ear vein injection 20 s after irradiation. Before observation HIFU irradiation, the irradiation process and immediately after irradiation, 1,2,5,10 min target sonogram, measured after irradiation with strong echo of each observation time point target area, and the analysis of the area tends to stable, the next at least 20 min after irradiation. The animals were sacrificed after 7 d, measurement of coagulation necrosis of the largest cross-sectional area and volume, and pathological examination of the specimens were taken necrosis. Explore the different irradiance sound power, the experimental and control groups target gray occurrence of different doses of SonoVue and coagulation necrosis rate of variation of target during irradiation and irradiation after hyperechoic area and the largest cross-sectional area of ??coagulation necrosis, compare different irradiation acoustic power SonoVue dose of the experimental group and the control group formed by coagulation necrosis volume, seek optimal sound power-SonoVue dose combination based on safety, efficiency conditions . 2, the use of MRI navigation HIFU treatment system, the treatment of head and operating frequency of 1.0 MHz, a focal length of 150 mm, 150 mm in diameter. Nanjiang Yellow 6, self-control, is divided into simple HIFU Joint saline treated group (control group) and HIFU combined with micro-bubble contrast agent SonoVue treatment group (experimental group). HIFU the irradiated sound of power early screening and SonoVue dose combination of goat liver MRI monitoring the HIFU sentinel irradiation baseline temperature goats before irradiation anal temperature. Record target tissue temperature rise rate of 5 s, 10 s at the focus of temperature, comparison of the experimental and control groups after irradiation during irradiation and after irradiation, and the next time after irradiation for at least 20 min. 7 d after the animals were killed, the measurement of coagulation necrosis largest cross-sectional area and volume, coagulation necrosis and surrounding normal liver tissue for pathological observation. A Comparative Study of the temperature of the experimental group and the control group for the area of ??the region above 56 ℃ with the respective differences, comparing the experimental and control groups the largest cross-sectional area of ??coagulation necrosis coagulation necrosis volume. Results: 1, under ultrasound monitoring, the HIFU joint the SonoVue injury goat liver, in the case to appear visible target hyperechoic change, sound power of 150 W, the control group and SonoVue dose: 0.01,0.03,0.05 ml / kg of The experimental group and the acoustic power of 250 W, the control group and SonoVue dose of 0.01 ml / kg of the experimental group, and 9 to 12 s after irradiation begins, the target echo enhancement began to appear. The sound power of 250 W, SonoVue dose 0.03,0.05 ml / kg of the experimental group and acoustic power of 350 W of the control group and SonoVue dose: 0.01,0.03,0.05 ml / kg, the experimental group, at the beginning of irradiation 2 ~ 5 s, target apparent echogenic. Target appeared hyperechoic area, the area gradually increases with irradiation time. Immediately after the end of the HIFU irradiation target hyperechoic area of ??maximum. Stop after irradiation, with the extension of the observation time, the range is gradually reduced, and the stabilized state. 2, immediately irradiated after the acoustic power of 150 W, the control group and SonoVue dose 0.01,0.03,0.05 ml / kg of the experimental group and the acoustic power of 250 W, the control group and SonoVue dose 0.01,0.03 ml / kg in the experimental group, was not observed in the target strong echo is moving toward the transducer. The sound power of 250 W, SonoVue dose of 0.05 ml / kg in the experimental group target hyperechoic moving toward the transducer, a distance of 3.0 ± 1.5 mm; sound power of 350 W, the control group,, and SonoVue dose of 0.01 0.03,0.05 ml / kg experimental group there are varying degrees to the direction of the transducer moving target hyperechoic moving distance were 5.4 ± 2.6 mm and 7.8 ± 2.4 mm and 11.6 ± 2.8 mm and 16.7 ± 3.8 mm, experiment Group targets hyperechoic moving toward the transducer distance compared with control group with a significant difference (P lt; 0.05), 350 W experimental group target hyperechoic moving toward the transducer distance with SonoVue dose increase big and gradually increases between SonoVue dose within the experimental group were statistically significant (P lt; 0.05). 3, respectively, of three irradiation sound power, the control group and the experimental group of different doses of SonoVue doing the target grayscale emergence rate and coagulation necrosis rate trend chi-square test analysis: sound power of 150 W, the experimental group target grayscale a rate greater than that of the control group and the experimental group increased with increasing SonoVue dose rate of coagulation necrosis of the experimental group compared with the control group no significant difference between the experimental group SonoVue dose between coagulation necrosis and no significant difference; sound power of 250 W, the the target grayscale emergence rate of the experimental group the coagulation necrosis rate greater than the control group and the experimental group as SonoVue dose increase large increase; sound power of 350W, the the target grayscale emergence rate of the experimental group and coagulation necrosis rate with the control group showed no significant difference in the experimental group, no significant differences between different SonoVue dose. It was also observed: in three irradiation acoustic power in the experimental group of different doses of SonoVue to target strong echo changes were observed but no coagulation necrosis formation; sound power to the control group of 250,350 W found that the form did not target hyperechoic with coagulation necrosis. 4, the sound power of 150 W, the control group and SonoVue dose of 0.01 ml / kg experimental group is difficult to form a coagulation necrosis, it can not be compared statistically coagulation necrosis of the largest cross-sectional area of ??the corresponding target strong echo area related , SonoVue dose 0.03,0.05 ml / kg the experimental group targets strong echo area 1 min after the irradiation stabilized, the stabilization of the target hyperechoic area consistent with the maximum cross-sectional area of ??coagulation necrosis; sound power 250 W, the control group and SonoVue dose of 0.01 ml / kg of the experimental group target hyperechoic area irradiated after 2 min stabilized SonoVue dose 0.03,0.05 ml / kg experimental group at the end of irradiation 5 min after stabilizing stabilization target hyperechoic area consistent with the maximum cross-sectional area of ??coagulation necrosis; sound power of 350 W, the control group and SonoVue dose of 0.01 ml / kg experimental group, target hyperechoic area 5 min after the end of the area in the irradiation stabilize, stabilize target hyperechoic area consistent with the maximum cross-sectional area of ??coagulation necrosis SonoVue dose 0.03,0.05 ml / kg experimental group to 10 min in the observation still not stabilized. 5, the sound power of 150 W, the control group and SonoVue dose of 0.01 ml / kg experimental group is difficult to form a coagulation necrosis, we are unable to statistically compare corresponding coagulation necrosis volume SonoVue dose 0.03,0.05 ml / kg experimental group The formation of coagulation necrosis volume were: 38.57 ± 5.74 mm ~ 3 and 56.54 ± 6.32 mm to 3 both have significant difference (P lt; 0.05). The sound power of 250 W, the control group and SonoVue dose 0.01,0.03,0.05 ml / kg experimental group formed by coagulation necrosis volume were: 86.68 ± 13.38 mm ~ 3,187.58 ± 21.55 mm ~ 3,279.41 ± 24.24 mm ~ 3 and 368.47 ± 36.24 mm to 3 between SonoVue dose experimental group and the control group, the experimental group were statistically significant difference (P lt; 0.05); sound power of 350 W, the control group and SonoVue doses of 0.01, 0.03,0.05 ml / kg experimental group formed by coagulation necrosis volume were: 257 ± 13.38 mm ~~ 3,390.04 ± 21.55 mm ~~ 3,568.68 ± 24.24 mm to 3 and 778.71 ± 36.24 mm to 3, the experimental group and the control group comparison between different SonoVue dose of the experimental group were statistically significant (P lt; 0.05). The same sound power coagulation necrosis volume of the experimental group were greater than the corresponding control group; SonoVue dose increase between the experimental group, formed by coagulation necrosis volume increases efficiency obviously. With HIFU by irradiation, the experimental and control groups were formed coagulation necrosis the hepatocyte nuclear pyknosis necrosis, fragmentation dissolved. Coagulation necrosis clear boundaries with the surrounding normal liver tissue, at the junction with visible inflammatory cell infiltration and fibroblast proliferation. The MRI monitoring HIFU experiment, the experimental group at the beginning of HIFU irradiation 2 ~ 5 s, the focus at temperatures significantly higher temperature rise rate is greater than the control group, the HIFU irradiation time, temperature increased slowly , irradiation after the highest temperature instantly 103.75 ± 8.61 ℃; control group after the start of irradiation, the temperature gradually increased, also reached a maximum temperature of 92.45 ± 6.12 ° C immediately after irradiation is stopped, they have a significant difference (P lt; 0.05). After the irradiation, with the extension of the observation time, the target temperature is gradually decreased. 8, in the MRI monitoring HIFU experiment, the experimental group and the control group, with the irradiation time, the temperature of the focal field at the area of ??a region above 56 ℃ gradually increases immediately after the irradiation is stopped reaches the maximum, respectively, 37.52 ± 4.83 mm ~ 2 and 12.35 ± 3.75 mm ~~ 2, they have a significant difference (P lt; 0.05). Anatomical formed the experimental group and the control group, the largest cross-sectional area of ??coagulation necrosis area were: 44.74 ± 7.61 mm ~ 2 and 16.32 ± 4.61 mm ~ 2, between the two there is a significant difference (P lt; 0.05). Coagulation necrosis area of ??the experimental and control groups were greater than the maximum cross-sectional area of ??the corresponding target temperature of 56 ° C above the area, the difference was significant (P lt; 0.05). Experimental group and a control group formed by coagulation necrosis volume were: 40.47 ± 8.96 mm ~ 3,216.398 ± 32.27 mm ~ 3, both with a statistically significant difference (P lt; 0.05). Conclusion: the end of time as well as irradiation during irradiation target grayscale the target grayscale emergence rate target hyperechoic become stable time is governed by HIFU irradiation of sound power and SonoVue dose. A. sound power is low, SonoVue can improve target gray emergence rate, contribute to the monitoring of the sonogram, when the sound power, compared with the control group, SonoVue appear to improve the target grayscale There was no difference. B. sound power and SonoVue dose, compared with the control group, ahead of time SonoVue make target grayscale, but loud power, no difference in the control group and the experimental group. Tends to a stable time after the end of the C. Irradiation target echo range gradually extended with the irradiation power and SonoVue dose increases, but in the loud power, high SonoVue dose, target echo range require considerable time to stabilize. But stable target hyperechoic area consistent with the maximum cross-sectional area of ??coagulation necrosis. The stabilization target hyperechoic area can evaluate the scope of the coagulation necrosis. Target hyperechoic to the movement of the transducer direction by irradiation of sound power and SonoVue dose irradiation power is large, SonoVue dose increases, target hyperechoic to the direction of the transducer moving distance significantly, increases the risk of side effects. 3, when the sound power is low, a low dose of SonoVue difficult to enhanced HIFU injury; When the sound power is larger, SonoVue significantly improve the efficiency of HIFU goat liver damage, and the same sound power, with the increase of SonoVue dose , formed by coagulation necrosis volume increases efficiency obviously. 4, the experimental and control groups were seen white coagulation necrosis formation, light microscope, coagulation necrosis zone with clear boundaries of normal liver tissue, formed by coagulation necrosis no difference. 5, compared to the other experimental groups, the acoustic power of 250 W, SonoVue dose for the experimental group of 0.03 ml / kg, and no target hyperechoic moving toward the transducer, and the formation of coagulation necrosis volume optimal sound power-SonoVue dose that is both safe and synergistic combination. 6, SonoVue can significantly improve the initial stage of the HIFU irradiation target tissue temperature rise rate, so that the irradiated tissue in a relatively short period of time to reach a high temperature, suggesting that SonoVue can enhance tissue absorption of ultrasound to accelerate energy deposition It helps to shorten the time and improve the treatment efficiency of coagulation necrosis formed. 7, only the critical temperature is not a good response organizations coagulation necrosis tissue by HIFU irradiation process, heat accumulation, suggesting that should be considered, the application of thermal dose instructions coagulation necrosis area.
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