Non-invasive targeted neuromodulation via focused ultrasound BBB permeabilization

通过聚焦超声 BBB 通透进行非侵入性靶向神经调节

• 批准号: 9768565
• 负责人: MARGARET S LIVINGSTONE
• 金额: $ 60.83万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-23 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768565
• 关键词: Ablation; Acoustics; Anatomy; Anesthesia procedures; Animals; Basic Science; Behavioral; Bicuculline; Blood - brain barrier anatomy; Blood Tests; Brain; Brain region; Butyric Acids; Clinical; Contralateral; Device Designs; Devices; Disease model; Dose; Electrophysiology (science); Evaluation; Evoked Potentials; Exhibits; Extravasation; Focused Ultrasound; Functional Magnetic Resonance Imaging; Globus Pallidus; Glutamates; Goals; Hour; Human; Image; Intravenous; Ipsilateral; Macaca; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Microbubbles; Modeling; Movement Disorders; Neuromodulator; Neurons; Neurotransmitters; Parkinson Disease; Pars Interna; Patients; Permeability; Primates; Rattus; Research; Saccades; Safety; Series; Signal Transduction; Somatosensory Cortex; Stimulus; Structure of subthalamic nucleus; System; Techniques; Testing; Thalamic structure; Thermal Ablation Therapy; Time; Tissues; Training; Translating; Tremor; Ultrasonography; Visual; Visual Pathways; analog; area striata; behavior measurement; chronic pain; clinical application; clinical translation; efficacy testing; frontal eye fields; gamma-Aminobutyric Acid; gaze; improved; intravenous injection; neuroregulation; painful neuropathy; response; somatosensory; superior colliculus Corpora quadrigemina

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.

项目摘要 该项目的目标是在猕猴身上测试一种非侵入性、安全、可逆的技术， 调节灵长类动物大脑中小的靶区域的神经元活动。我们开发并测试了 在猕猴中，用于瞬时打开靶脑区域中的血脑屏障（BBB）的技术 在不造成任何损伤的情况下，使用临床可用的聚焦超声设备， 循环的微气泡我们现在建议将联合收割机这种短暂的血脑屏障开放与系统性的 施用通常不穿过BBB的神经活性物质，以测试这些物质是否 将仅在具有透化BBB的区域中具有神经活性作用。我们测试了BBB 我们已经在猕猴中广泛使用透化技术，并且我们已经测试了结合BBB的技术， 透化和神经调节。该项目的目标是扩展神经调节 技术，以优化参数在猕猴的临床适用性，以测试这种技术在一个 疾病模型，并在大鼠中测试兴奋性和抑制性神经调节。这项技术将 对于基础研究很重要，更重要的是，可以直接移植到人类患者身上进行神经消融 规划