| High intensity focused ultrasound (HIFU) treatment have been used in sorts of tumor and non-tumor disease. In the practice of tumor therapy especially for tumor locating deeply in body or tumor with a large volume, HIFU was a time-consuming therapeutic method and the curative effect was away from ideal. Many methods have been explored to elevate HIFU therapeutic efficiency, but they were not acceptable to patients for their shortcoming. A few researchers had confirmed that microbubbles could enhance HIFU damage to tissue in vivo, but the experiments they had done were not comparable with clinical therapy. At first, we prepared a phased shift perfluorocarbon emulsion (PSPE) in this study, and elementarily observed its physico-chemical property and acute toxicity of experimental animal. Then we used PSPE intravenously before extracorporeal HIFU irradiation, and observed the change of HIFU damaging efficiency in normal animal liver, kidney and liver tumor. It were also studied such as real-time monitoring with two-dimensional ultrasonography in HIFU irradiating process, pathological changes and pathological prognoses of targeting region of HIFU, functional and structural changes of important organ of experimental animals. 1. Preparation of a intravenously injectable PSPE and its acute toxicity experiment of animal Using dodecafluorocarbon (DDFP) as a disperse phases, water as disperse medium, Pluoronic F68 and lecithin as main emulsifying agent, high speed agitating as disperse method, optimizing formation with orthogonal experiment, we prepared a phase shift perfluorocarbon emulsion. The mean diameter of the emulsion droplets was 1.69±0.85 μm, the mean concentration was 2.85±0.37×1010 per milliliter, PH was 7.48±0.13. The inner phase of droplets was liquid under common temperature, if the temperature of the droplets were up to 29.3°C or the droplets were irradiated by acoustic wave, liquid DDFP in the droplets should shift to gas, and the droplets should formed microbubbles. The droplets' concentration of this PSPE decreased with the lengthening of storage time, the droplets' mean diameter enlarged and PH had no marked change. 34 New Zealand hybrid rabbits as experimental animal, LD50 was determined using approximate method, the LD50 of this PSPE was 0.37 ml/kg. In experiment to determine the LD50, a main toxicity of the PSPE was observed, it was dyspnea. Hyperinflated non-collapsible lungs (HNCL) were found after autopsy, and histologic examination found dilation of alveoli pulmonis, parts of alveoli pulmonis disrupted, lung interstitial was compressed. Conclusions: (1) PSPE providing for experiments could be prepared by high speed agitating method; (2) The PSPE's quality decreased with the lengthening of storage time; (3) The PSPE's LD50 was 0.37 ml/kg; (4) The acute toxicity of this PSPE was lung embolism; (5) The droplets' diameter must be cut down by refining the preparation methods. 2. Experimental study of normal tissues damaging with HIFU and PSPE 2.1 Experimental study of normal rabbit liver damaging with HIFU and PSPE JC HIFU tumor therapy system (Chongqing Haifu Technology, Chongqing, China) was used. The parameters of therapeutic transducer were: frequency-0.7MHz, focal length-135mm, acoustic power-200W. Liver of 62 New Zealand rabbits were irradiated extracorporeally by HIFU after intravenously injecting a dose of PSPE. Own control method was used.Animals in experimental group were intravenously injected a dose of PSPE, in control group were intravenously injected a identical dose of physiologic saline, then HIFU irradiation were performed in both groups' animals. To every rabbits, control group experiment performed prior to experimental group. Adopted HIFU irradiating mode was dot-mode. Irradiating depth was 20mm. Echoes of HIFU targeting regions were observed, sizes of the hyperechoic region were measured and gray-scale values were recorded. Rabbits were sacrificed 3 days later, sizes of coagulative lesions were measured and EEFs were calculated. Specimens of lesions were collecte...
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