Cavitation dose painting for focused ultrasound-induced blood-brain barrier disruption.
Cavitation dose painting for focused ultrasound-induced blood-brain barrier disruption.
复制标题
用于聚焦超声引起的血脑屏障破坏的空化剂量涂敷。
DOI：
10.1038/s41598-019-39090-9
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发表时间：
2019
影响因子：
4.6
通讯作者：
Chen,Hong
中科院分区：
文献类型：
--
作者：
Yang,Yaoheng;Zhang,Xiaohui;Ye,Dezhuang;Laforest,Richard;Williamson,Jeffrey;Liu,Yongjian;Chen,Hong
聚焦超声结合微泡破裂血脑屏障（FUS-BBBD）是一种很有前途的无创脑局部给药技术。这项研究表明，被动空化成像（PCI）是能够预测的位置和浓度的纳米团簇交付FUS-BBBD。在小鼠的FUS-BBBD治疗期间，通过超声成像系统被动检测来自FUS激活的微泡的声发射，并使用频域PCI算法离线处理。在FUS处理后，将放射性标记的金纳米簇64 Cu-AuNC静脉注射到小鼠中，并通过正电子发射断层扫描/计算机断层扫描（PET/CT）成像。PCI获得的稳定空化剂量（SCD）图中心与PET获得的64 Cu-AuNCs浓度图中心在FUS束的横向和轴向分别在0.3 ± 0.4 mm和1.6 ± 1.1 mm范围内重合。发现SCD图与64 Cu-AuNCs浓度图在逐像素水平上线性相关。这些研究结果表明，SCD地图可以在空间上“画”交付的纳米团簇浓度，我们命名为空化剂量绘画技术。这种基于PCI的空化剂量绘制技术与FUS-BBBD相结合，开辟了空间靶向和调制脑药物递送的新视野。
Focused ultrasound combined with microbubble for blood-brain barrier disruption (FUS-BBBD) is a promising technique for noninvasive and localized brain drug delivery. This study demonstrates that passive cavitation imaging (PCI) is capable of predicting the location and concentration of nanoclusters delivered by FUS-BBBD. During FUS-BBBD treatment of mice, the acoustic emissions from FUS-activated microbubbles were passively detected by an ultrasound imaging system and processed offline using a frequency-domain PCI algorithm. After the FUS treatment, radiolabeled gold nanoclusters,64Cu-AuNCs, were intravenously injected into the mice and imaged by positron emission tomography/computed tomography (PET/CT). The centers of the stable cavitation dose (SCD) maps obtained by PCI and the corresponding centers of the64Cu-AuNCs concentration maps obtained by PET coincided within 0.3 ± 0.4 mm and 1.6 ± 1.1 mm in the transverse and axial directions of the FUS beam, respectively. The SCD maps were found to be linearly correlated with the64Cu-AuNCs concentration maps on a pixel-by-pixel level. These findings suggest that SCD maps can spatially “paint” the delivered nanocluster concentration, a technique that we named as cavitation dose painting. This PCI-based cavitation dose painting technique in combination with FUS-BBBD opens new horizons in spatially targeted and modulated brain drug delivery.