| BACKGROUNDHigh intensity focused ultrasound (HIFU) treatment have been used in sorts of tumor and non-tumor disease.The tissue of target region would absorb the energy of the supersonic wave and be destroyed while the tissue out of the target region would not be destroyed. But in tumor therapy especially those deeply located in body or with a large volume, HIFU was a time-consuming therapeutic method and the curative effect was far from ideal. Rencently , it was confirmed that microbubble agent was an enhancement agent of HIFU theraphy and the efficiency of HIFU theraphy was directly related to microbubble concentration in tissue . However, with increasing microbubble dosage,the microbubble concentration in the tissue is higher which brings more danger of tissue damge. The novel microbubble agent SonoVue(BR-1, Bracco, Milan, Italy) combined with HIFU theraphy on goat's live was used to select a equilibrium point which could ensure the safty and enhancing therapeutic efficacy to the most degree thus provids a feasible scheme to clinic therapy.OBJECTIVE1. To investigate the security of different acoustic power–SonoVue dosage for HIFU enhanced theraphy combined with microbubble on goat's liver.2. To investigate enhancement effect of different acoustic power–SonoVue dosage for the HIFU enhanced theraphy combine with microbubble on goat's liver on base for the security。3. Based on results of 1 and 2 to select the mathching which could ensure the safety and enhancing therapeutic efficacy to the most degree in order to provide a feasible scheme to clinic therapy.4. To select the best scheme of line scan which could ensure the safety and enhancing therapeutic efficacy to the most degree under the best matching in order to provide a feasible scheme to clinic therapy.METHODS1. JC HIFU tumor therapy system was used. The parameters of therapeutic transducer were: frequency-0.8MHz,focal length-138mm, diameter- 200mm ,acoustic power -150W,250W,350W, irradiating time- 15s, HIFU irradiating Mode was dot .35 Nanjiang goats were adopted, own control was used in this study. SonoVue dosage of experiment group were 0.01ml/kg, 0.03ml/kg and 0.05ml/kg.The control group received an injection of normal saline(NS)of the same volume. In all animals, control experiments were performed prior to experiments of experimental group. Both group was performed 20s after injection, the time interval between two irradiation was 20 minutes to ensure the drug elimination. Echo changes of HIFU targeting region and the position of the focal region were observed, the vertical distance of the focal center to the capsula fibrosa was measured by computer。Animals were sacrificed and dissected 1 week later and length of necrotic region and the vertical distance of the lnecrotic region center to the capsula fibrosa were measured. The remove distance and rate of unceptable excursion were caculated. The optimum matcing was slectd which could ensure the precise location of the coagulation necrosis。SPSS and excell statistical software was performed for the statistical analysis.2. 45 Nanjiang goats were adopted,and the parameters of therapeutic transducer was the same as above.HIFU irradiating Mode was dot.The irradiating time was 15s . SonoVue dosage of experiment group were 0.01ml/kg, 0.03ml/kg and 0.05ml/kg,while the control group was injected with normal saline(NS)of the same volume. Own control was applied in this study to investigate the security of sound path .Echo changes of corresponding skin of HIFU targeting region were observed, and thickness of the skin was measured at the same time. The skin was observed mediatly and 1W after irradiation. Animals were sacrificed and dissected 1 week later, histological inspection of skin,capsula fibrosa,the surface muscle of rib was performed. Distance of the rib was measured and tissue around liver was observed. Echo range of insecurity skin and the rate of insecurity skin was caculated.The optimum matching was selected which could ensure the security of the skin. SPSS and excell statistical software was performed for the statistical analysis3. 45 Nanjiang goats were adopted to select the mathching which could enhancing therapeutic efficacy to the most degree based on security. The parameters, SonoVue dosage and irradiating Mode of therapeutic transducer were the same as obove. Animals were sacrificed and dissected 1 week later , size of necrotic regions were measured and EEFs were caculated. Specimens were collected for histological inspection. SPSS and excell statistical software was performed for the statistical analysis.4. 12 Nanjiang goats were randomized to four groups for the study of different line scan mode: line scan (speed :3mm/s,irradiating time:30s), continuous dot (irradiating 3s ,stop 3s,total irradiating time:30s ),line scan under rear background (after 5s dot scan of back position ,line scan for 3mm/s,30s),line scan under beside background(after 5s dot scan of beside position,line scan for 3mm/s,30s), SonoVue dosage :0.03ml/kg ,acoustic power :250W, length of line:1cm.to select the best line scan mode which could enhance therapeutic efficacy at most degree base for the security.RESULTS 1. Experimental dots were more likely to shift than the control dots.Under the same acoustic power ,the shifting distance increased with SonoVue concentration.And it depended more on SonoVue dosage with increasing acoustic power.2. Under 250W-0.05ml/kg and 350W-0.05ml/kg , the rate of unacceptable coagulation necrosis excurtion was significant greater than the control group, there were unacceptable shift for 60% and 80% of the dots and quite large area for coagulation necroside outside the expected lesion area which meant that the two matching were not suitable for HIFU theraphy.3. It was presented by correlation analysis that skin echo was directly related to the degree of scald . the Spearman correlation coefficent was 0.993,and the encho range of the scald degree aboveⅡdegree superficial scald was 19-34.4. Under 350w - 0.03ml/kg,350w - 0.05 ml/kg, the rate of unacceptable scald(66.7% and 80%) was significant than the control group , while there was no prominent difference between the experimental and control groups (less than 20%) in the rest matching which suggested that the two matching groups could not ensure the security of the skin while irradiation.5. There was no superfluity infection to the tissue of sound path and around liver under different acoustic power–SonoVue dosage for the HIFU enhanced theraphy combined with microbubble on goat's liver .6. The rest matching could ensure the security under irradiation except 250W-0.03ml/kg,250W-0.05 ml/kg,350W-0.05ml/kg.7. It was proved that SonoVue could enhance the lesion of goat's liver in all experimental groups except 150W - 0.01ml/kg. 250W-0.03ml/kg matching could enhance therapeutic efficacy to the degree based on the security as its EEF was found to be the smallest .8. It was proved the lesions in goat's liver in both experimental group and control group were typical and inreversible necrosis.9. Under the best matching 250W-0.03ml/kg irradiation condition, line scan under rear background was the best mode compared to other three line scan mode , and could enhance therapeutic efficacy to most degree based on security.CONCLUSION1. Microbubble could effectively increase the size of the HIFU lesions, but lesion shift should be carefully considered while performing HIFU ablations.2. The matching 250W-0.03ml/kg was the optimum condition which could enhance therapeutic efficacy to the most degree based on security.3. Two-dimensional ultrasonography was benefit to real time monitoring to skin in HIFU treatment.4. The lesions in goat's liver caused by HIFU combined with SonoVue were typical necrosis;5. Line scan under rear background was the best mode which could enhance therapeutic efficacy to the most degree based on security.
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