【作者】 卞伟； 支兴刚； 王智彪； 白晋； 李发琪； 谭启华； 李崇雁；

【机构】 重庆市肿瘤医院神经外科； 重庆医科大学附属第一医院神经外科； 重庆医科大学医学超声工程研究所；

【摘要】 目的: 通过研究高强度聚焦超声(High intensity focused ultrasound,HIFU)对正常免脑组织作用后损伤灶的病理转归,探讨其治疗脑肿瘤的安全性和可行性。方法: 以CZF-II型超声治疗仪作为HIFU聚能器,作用时均采用其最大输出功率5W和相应的最适配置。实验分两步进行。首先在HIFU辐照总时间不变的情况下,用不同的分次时间多次对24只新西兰兔脑组织进行定位损伤。观察实验兔的反应及生存状况,5周后处死取材,用氯化三苯基四氮 (triphenyl tetrazolium choloride,TTC)染色,观察靶点及周围组织的大体表现后．固定标本,做5微米石蜡切片, 常规HE染色,光镜下观察组织学变化。然后根据第一步的实验结果,选取合适的HIFU作用剂量,对另12只新西兰兔脑组织进行照射,分别于即刻、3天、7天、14天、28天及60天处死取材,大体和组织学观察照射后损伤灶的生物学特性及靶区组织病理学变化,并在电镜下观察损伤即刻的超微结构变化。结果:观察期内实验兔的生存状态在单次作用时间≥20s后明显变差,与作用次数无明显关系,说明新西兰兔能耐受<5W×20s的HIFU照射,组织学变化提示最佳作用时间为5-10s。在病理转归的研究中,采用相同实验条件,以单次作用时间5s和10s为研究对象,大体观察发现二者造成的损伤范围不同,以28天差异最大,光镜下早期表现比较一致,也于28天出现不同变化,最终10s区转归为神经胶质瘢痕,5s区则未见明显损伤痕迹。在HIFU 损伤即刻,电镜下可见二者损伤程度不同,10s区表现为细胞、血管结构完整性受破坏,而5s作用区仍具有完整性。结论:脑组织对HIFU损伤的耐受与单次作用剂量有关,而与作用次数和性别无关。HIFU能定位损伤深部脑组织,对浅表组织的影响较小。损伤灶的修复方式与照射的剂量有关, 在适当剂量作用下脑组织的损伤是可恢复的,提示用HIFU 治疗脑肿瘤是安全的和可行的,为将来应用HIFU临床治疗脑肿瘤提供了实验依据。HIFU能定位损伤大脑深部组织, 对浅表组织的影响较小。损伤灶的修复方式与照射的剂量有关,提示用适当剂量HIFU治疗脑肿瘤是安全的和可行的, 为将来应用HIFU临床治疗脑肿瘤提供了实验依据。更多还原

【Abstract】 Objective: To study pathological regression of normal New Zealand Rabbits’ brain tissue after HIFU ablation to observe if it is secure and effective to treat the intracranial neoplasm. Methods: The CZF-II type ultrasound therapeutic apparatus was used as the HIFU creator, and we selected the maximum power 5 watt with its most suitable parameter in the experiment The experiment was carried out in two steps. Firstly under the same total time of HIFU exposure, we used the different divided tune to ablate localized on brain tissue of 24 New Zealand white rabbits several times, observing the rabbits’ reaction and living status, and all was killed after 5 weeks, using TTC stain to observe the visual changes and HE stain to observe histological changes in microscope. Then according to the first step’ s result, we selected some suitable dose of HIFU exposure to ablate on other 12 rabbits’ localized brain tissue, and killed them successively in immediately, 3 d, 7 d, 14d, 28d, 60d after sonication, observing target lesion with visual and histological method to identity the biological characteristic and pathologic changes of target lesion. We also observed the ultrastructure changes immediately after sonication. Results: During the observation period, the rabbits’ living status apparently became worse when the time is ≥20s each exposure. The times of exposure are not relevant to living status. It is said that the New Zealand Rabbit could endure the dose of HIFU exposure < 5W ×20s, and the histological change clued to the best exposure time was 5 - 10s. Adopting the same experimental condition in the pathologic regression research, and taking the 5s and 10s of each exposure time as the studying objects, we found different dimension of lesions between two exposure time by visual, especially on 28d, so did they display in microscope though they had the almost same appearance in early period. Finally the 10s area became scar of glia and no apparent lesion traces were found in the 5s area. In electron microscopy we saw different level of lesion between them, that the integrality of the cell and vascular structure were destructive in 10s area, but remained in 5s area. Conclusion: The toleration of brain tissue for HIFU exposure is relevant to single time of sonication, and is independence of times of exposure. HIFU can localized ablate deep brain tissue, but little effect to superior tissue. The restoring method of lesion due to the dose of exposure, that the lesion of brain is reversible when the suitable dose is used. As a Conclusion, it is security and effective to use suitable dose of HIFU in the treatment of intracranial neoplasm and the experiments provide important data in future clinical treatment更多还原