Yang Feng-Yi, Horng Shih-Cheng
Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan.
Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:5573-6. doi: 10.1109/IEMBS.2011.6091348.
The purpose of this study was to evaluate the permeability of the blood-brain barrier (BBB) after focused ultrasound (FUS) exposure and to investigate if such an approach increases the tumor-to-ipsilateral brain permeability ratio. Normal rats and F98 glioma-bearing rats were injected intravenously with Evans blue (EB); these treatments took place with or without BBB disruption induced by transcranial FUS of one hemisphere of the brain. Sonication was applied at an ultrasound frequency of 1 MHz with a 5% duty cycle, and a repetition frequency of 1 Hz. The permeability of the BBB was quantitatively assessed by means of the extravasation of EB. Contrast-enhanced MR images were used to monitor the gadolinium deposition path associated with transcranial FUS and the influence of size and location was also investigated. Furthermore, whole brain histological analysis was performed. The results were compared by two-tailed unpaired t test. The accumulation of EB in brains and the tumor-to-ipsilateral brain permeability ratio of EB were significantly increased after FUS exposure. EB injection followed by sonication showed an increase in the tumor-to-ipsilateral brain ratio of the target tumors of about two-fold compared with the control tumors on day 8 after tumor implantation. MR images showed that FUS locally enhances the permeability of the BBB in the glioma-bearing rats. The BBB can be locally disrupted with FUS in the presence of microbubbles. This technology may offer new opportunities that will allow enhanced synergistic effects with respect to other brain tumor treatment regimens.
本研究的目的是评估聚焦超声（FUS）照射后血脑屏障（BBB）的通透性，并研究这种方法是否会增加肿瘤与同侧脑的通透性比值。对正常大鼠和荷F98胶质瘤大鼠静脉注射伊文思蓝（EB）；这些处理在有或没有通过对大脑一个半球进行经颅FUS诱导血脑屏障破坏的情况下进行。超声以1 MHz的频率、5%的占空比和1 Hz的重复频率进行照射。通过EB的外渗对血脑屏障的通透性进行定量评估。使用对比增强磁共振图像监测与经颅FUS相关的钆沉积路径，并研究大小和位置的影响。此外，还进行了全脑组织学分析。结果通过双尾非配对t检验进行比较。FUS照射后，脑中EB的蓄积以及EB的肿瘤与同侧脑通透性比值显著增加。在肿瘤植入后第8天，与对照肿瘤相比，EB注射后进行超声照射显示目标肿瘤的肿瘤与同侧脑比值增加了约两倍。磁共振图像显示，FUS可局部增强荷胶质瘤大鼠血脑屏障的通透性。在存在微泡的情况下，FUS可局部破坏血脑屏障。这项技术可能会提供新的机会，从而在其他脑肿瘤治疗方案方面实现增强的协同效应。
