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Observed Effects of Whole-Brain Radiation Therapy on Focused Ultrasound Blood-Brain Barrier Disruption.
Ultrasound in Medicine & Biology ( IF 2.9 ) Pub Date : 2020-05-22 , DOI: 10.1016/j.ultrasmedbio.2020.04.013
Phillip Jason White 1 , Yong-Zhi Zhang 1 , Chanikarn Power 1 , Natalia Vykhodtseva 1 , Nathan McDannold 1
Affiliation  

As focused ultrasound for blood–brain barrier disruption (FUS-BBBD) has progressed to human application, it has become necessary to consider the potential effects of prior irradiation treatments. Using a murine model, we examined the effects of whole-brain irradiation on FUS-BBBD. We first subjected half of the experimental cohort to daily 3-Gy whole-brain irradiation for 10 consecutive days. Then, microbubble-assisted FUS-BBBD was performed unilaterally while the contralateral sides served as unsonicated controls. FUS-BBBD, as evident by measuring the fluorescence yield of extravasated trypan blue dye, was identified at all sites with minimal or no apparent pathology. The peak fluorescence intensity caused by extravasated dye in the sonicated region was 17.5 ± 12.1% higher after radiation and FUS-BBBD than after FUS-BBBD alone, suggesting that prior radiation of the brain may be a sensitizing factor for FUS-BBBD. Radiation alone—without FUS-BBBD—resulted in mild BBB disruption. Hemorrhagic petechiae were observed in 9 of 12 radiated brains, with 77% of them clearly located outside the sonicated area; no petechiae were found in non-irradiated animals. This radiation protocol did not appear to increase the risk for vascular damage associated with FUS-BBBD.



中文翻译:

观察全脑放射治疗对聚焦超声血脑屏障破坏的影响。

随着用于血脑屏障破坏的聚焦超声 (FUS-BBBD) 已经发展到人类应用,有必要考虑先前辐射治疗的潜在影响。使用小鼠模型,我们检查了全脑照射对 FUS-BBBD 的影响。我们首先让一半的实验组连续 10 天每天接受 3-Gy 全脑照射。然后,单侧进行微泡辅助 FUS-BBBD,而对侧作为未超声处理的对照。FUS-BBBD,如通过测量外渗台盼蓝染料的荧光产率所证明的,在具有最小或没有明显病理的所有位点被鉴定。辐射和 FUS-BBBD 后超声处理区域中由外渗染料引起的峰值荧光强度比单独 FUS-BBBD 后高 17.5 ± 12.1%,表明先前的大脑辐射可能是 FUS-BBBD 的敏感因素。单独的辐射——没有 FUS-BBBD——会导致轻微的 BBB 中断。在 12 个辐射脑中的 9 个中观察到出血性瘀点,其中 77% 明显位于超声处理区域之外;在未受辐照的动物中未发现瘀点。该辐射方案似乎不会增加与 FUS-BBBD 相关的血管损伤风险。

更新日期:2020-06-25
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