Non-invasive targeted neuromodulation via focused ultrasound BBB permeabilization

项目摘要 拟议项目的目标是在猕猴身上测试一种非侵入性、安全、可逆、 灵长类动物大脑小靶区神经元活动的调节。我们已经开发并测试了 猕猴的一种在目标脑区瞬间打开血脑屏障(BBB)的技术 在不造成任何损害的情况下，将临床上可用的聚焦超声设备与 循环中的微泡。我们现在建议将这种暂时的血脑屏障开放与系统性的 注射通常不通过血脑屏障的神经活性物质，以测试这些物质是否 仅在具有通透性血脑屏障的区域有神经活性作用。我们已经测试了血脑屏障 通透性技术在猕猴中广泛存在，我们已经测试了结合血脑屏障的技术 大鼠的通透性和神经调节。这个项目的目标是延长神经调节 技术应用于猕猴，以优化猕猴的参数以实现临床适用性，并在 疾病模型，并在大鼠身上测试兴奋性和抑制性神经调节。这项技术将是 对基础研究很重要，更重要的是，可以直接翻译给人类患者进行神经消融 计划。

Project Summary The goal of the proposed project is to test in macaques a technique for non-invasive, safe, reversible, modulation of neuronal activity in small targeted regions of the primate brain. We have developed and tested in macaques a technique for transiently opening the blood-brain barrier (BBB) in targeted brain regions without causing any damage, using a clinically available focused ultrasound device in conjunction with circulating microbubbles. We now propose to combine this transient BBB opening with the systemic administration of neuroactive substances that normally do not cross the BBB to test whether these substances will have neuroactive effects only in the region with permeabilized BBB. We have tested the BBB permeabilization technique extensively in macaques, and we have tested the technique of combining BBB permeabilization and neuromodulation in rats. The goal of this project is to extend the neuromodulation technique to macaques, to optimize parameters in macaques for clinical applicability, to test this technique in a disease model, and to test in rats both excitatory and suppressive neuromodulation. This technique will be important for basic research, and, more importantly, directly translatable to human patients for neuro-ablation planning.