Basic research to sonodynamic therapy for the brain tumor

提出了一种治疗脑肿瘤的声动力学方法。在临床应用之前，我们进行了研究，以阐明声动力方法是否会引起正常大脑的组织损伤，并证明它对实验性脑肿瘤的有效性。1)在大鼠正常脑组织中，加或不加Rosebengal的超声聚焦照射均可引起局部破坏性病变，病变的发生与超声强度和照射时间成正比。2)病灶恰好发生在聚焦超声照射区域，聚焦基底节区时病灶离散，组织学检查可见凝固性坏死。服用Rosebengal后，病变变大并伴有局灶性出血。3)超声辐照对大鼠脑组织的损伤机制主要是由于与超声辐照有关的热效应，在超声辐照过程中，大鼠脑组织温度显著升高。超声照射后，给予Rosebengal的病变比未给予Rosebengal的病变变大，因此病变是空化效应和热效应诱导的，因为在有和没有使用Rosebengal的照射之间没有观察到脑温度的差异。4)Evans蓝增强的病变比没有使用Rosebengal的病变变大，这表明由于声化学活性，血脑屏障打开了。5)超声强度为100 w/cm^2，持续5分钟，1 h和24 h后病变相同，可引起破坏性病变。24 w/cm^2照射5分钟，2个月后未见破坏性病变或脱髓鞘病变。6)声化学对大鼠脑肿瘤的作用，经聚焦照射后，肿瘤呈梭状或新月形，表明肿瘤缩小，Rosebengal给药后效果更明显。这些结果表明声动力疗法对大鼠脑肿瘤的治疗是有效的。声动力治疗是近年来发展起来的脑肿瘤治疗方法之一，术中声动力照射也可用于残余肿瘤的治疗。少

A sonodynamic approach has been proposed for the treatment of brain tumors. Prior to clinical application, investigations were made to clarify whether or not the sonodynamic approach might induce tissue damage in the normal brain and demonstrate how effective it was on experimental brain tumor in rats. 1) In the normal brain tissue of rats, focused ultrasound irradiation with or without Rosebengal induced localized destructive lesions and the occurrence or lesions was proportional to the intensity of the ultrasound and the irradiation time. 2) The lesions which coincidentally occurred in the area irradiated with focused ultrasound, was discrete when focusing on the basal ganglia and coagulation necrosis was observed in the histological examination. After Rosebengal was administered, the lesions became larger and associated with focal hemorrhage. 3) The mechanism of tissue damage was considered to mainly be due to the heat effect relation to ultrasound irradiaton, because the brain temp … More erature increased remarkably during ultrasound irradiation. Following ultrasound irradiation, the lesions became larger with Rosebengal administration than without Rosebengal, and thus the lesions were induced with a cavitation effect as well as a heat effect, because no difference was observed in the brain temperature between irradiation with and without Rosebengal. 4) The lesions enhanced by Evans blue became larger with Rosebengal than without Rosebengal, thus suggesting an opening of the blood brain barrier due to sonochemical activity. 5) The intensity of ultrasound, which induced destructive lesions, was of 100 w/cm^2 for 5 minutes and the lesion was the same after 1 hour and 24 hours. With an irradiation intensity of 24 w/cm^2 for 5 minutes, none of the destructive or demyelinating lesions were found 2 months later. 6) In terms of the sonochemical effect to brain tumors in rats, the tumors turned into either a fusiform or a crescent after forcused irradiation, thus suggesting a reduction in the tumor which was more significant after Rosebengal administration. These results indicated that sonodynamic therapy was thus effective for the treatment of brain tumors in rats. Sonodynamic therapy is one of newly developed treatment modalities for brain tumors and it might be also applicable to residual tumors by means of intraoperative sonodynamic irradiation. Less