Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array.
Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array.
复制标题
使用 1 MHz 超声相控阵在猕猴中打开小体积血脑屏障。
DOI：
10.1016/j.jconrel.2023.10.015
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Caskey,CharlesF
中科院分区：
文献类型：
--
作者：
Manuel,ThomasJ;Sigona,MichelleK;Phipps,MAnthony;Kusunose,Jiro;Luo,Huiwen;Yang,Pai-Feng;Newton,AllenT;Gore,JohnC;Grissom,William;Chen,LiMin;Caskey,CharlesF
使用聚焦超声打开血脑屏障（BBB）有可能将药物输送到大脑的特定区域。BBB开口的尺寸和定位开口的能力决定了空间范围，并且在需要靶向小的脑区域的BBB开口的许多应用中是限制因素。在这里，我们评估了为小开口体积设计的系统的性能，并强调了与推动这种技术的空间精度相关的独特挑战。为了实现猕猴大脑皮层区域的小体积开口，我们测试了集成到磁共振图像引导聚焦超声系统中的自定义1 MHz阵列换能器。使用实时空化监测，我们证明了12例单次超声处理，小体积血脑屏障开放，皮质和皮质下靶区的平均体积分别为59 ± 37 mm3和184 ± 2 mm3。当结合灰质分割时，我们发现特定于受试者的声学模拟与观察到的开口之间存在高度相关性（R2= 0.8577），并且基于模拟的BBB开口阈值为0.53 MPa。基于MRI的安全评估和空化信号的分析表明，1 MHz BBB开放的安全压力范围，并表明我们的系统可用于向小的脑区域提供药物和基因治疗。
The use of focused ultrasound to open the blood-brain barrier (BBB) has the potential to deliver drugs to specific regions of the brain. The size of the BBB opening and ability to localize the opening determines the spatial extent and is a limiting factor in many applications of BBB opening where targeting a small brain region is desired. Here we evaluate the performance of a system designed for small opening volumes and highlight the unique challenges associated with pushing the spatial precision of this technique. To achieve small volume openings in cortical regions of the macaque brain, we tested a custom 1 MHz array transducer integrated into a magnetic resonance image-guided focused ultrasound system. Using real-time cavitation monitoring, we demonstrated twelve instances of single sonication, small volume BBB opening with average volumes of 59 ± 37 mm3and 184 ± 2 mm3in cortical and subcortical targets, respectively. We found high correlation between subject-specific acoustic simulations and observed openings when incorporating grey matter segmentation (R2= 0.8577), and the threshold for BBB opening based on simulations was 0.53 MPa. Analysis of MRI-based safety assessment and cavitation signals indicate a safe pressure range for 1 MHz BBB opening and suggest that our system can be used to deliver drugs and gene therapy to small brain regions.