Low Intensity Focused Ultrasound Neuromodulation

低强度聚焦超声神经调节

• 批准号: 9245142
• 负责人: William Jeffrey Elias
• 金额: $ 24.69万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9245142
• 关键词: Ablation; Acoustics; Affect; Animal Model; Brain; Brain Mapping; Cell Nucleus; Clinical; Clinical Trials; Corticospinal Tracts; Coupled; Disease; Electrophysiology (science); Elements; Essential Tremor; Evoked Potentials; Family suidae; Focused Ultrasound; Focused Ultrasound Therapy; Frequencies; Functional disorder; Future; Health; Heating; Histology; Human; Internal Capsule; Journals; Laboratories; Lesion; Location; Magnetic Resonance Imaging; Maps; Measures; Mechanics; Medicine; Mental disorders; Methods; Modality; Modeling; Monitor; Motor; Motor Cortex; Neuraxis; Neurologic; Neurons; Neurosciences; New England; Nuclear; Paresthesia; Pathway interactions; Patients; Physiologic pulse; Procedures; Property; Publishing; Pulse Pressure; Resolution; Rodent; Safety; Sensory; Somatosensory Cortex; Somatosensory Evoked Potentials; Sonication; Structure; Symptoms; System; Techniques; Technology; Temperature; Testing; Thalamic structure; Thermometry; Time; Tissues; Translating; Tremor; Ultrasonography; Work; animal model development; base; brain circuitry; cranium; design; experience; image guided; innovation; nervous system disorder; neural circuit; neuroregulation; new therapeutic target; receptive field; relating to nervous system; research study; somatosensory; tool

PROJECT SUMMARY / ABSTRACT Neuromodulation, or the manipulation of the brain's circuitry, has proven to be a powerful tool in neuroscience and for the treatment of neurologic disease. Current methods for neuromodulation in the brain can be limited by the skull, invasive delivery to the deep structures or by inadequate spatial resolution. Recently, ultrasound technology has advanced such that acoustic energy can be precisely delivered through the intact human skull. Our group has used high intensity focused ultrasound (HIFU) to perform stereotactic thalamic ablations through the intact skull for the treatment of severe tremor in humans. During these transcranial HIFU procedures, we observed neuromodulation of the ventrolateral thalamus with temporary suppression of tremor and paresthesia, but the mechanism of effect was likely thermal. Low intensity focused ultrasound (LIFU) utilizes different properties where neural tissue is affected by mechanical properties and without heat or damage to the brain. Thus, we hypothesize that low intensity focused ultrasound can be used for reversible, safe, and precise neuromodulation of deep brain circuits making it an ideal modality for non-invasive brain mapping. To prove this hypothesis, we have designed experiments where LIFU neuromodulation will be tested and optimized in a large brain, swine model. Firstly, systematic adjustments of the amplitude of pulse pressure or duration of LIFU delivered to the sensory thalamus will be used to differentially inhibit or augment these somatosensory pathways measured by evoked potentials. Theoretically, LIFU can also be targeted to axonal pathways like the corticospinal tract in the internal capsule instead of to nuclear targets to similarly manipulate the motor system. The development of an animal model to systematically optimize subcortical neuromodulation is unique. Our initial results have suppressed a deep brain circuit as evidenced by transiently reduced somatosensory evoked potentials and LIFU is capable of mapping the receptive fields of the somatosensory thalamus. We will also be able to explore different parameters with shorter duration and more bursting, which presumably will activate neuronal tissue or augment SSEP. This project in swine will optimize the technique of subcortical LIFU neuromodulation and confirm its safety so that it can be immediately implemented during stereotactic focused ultrasound thalamotomy procedures in humans. The relevance of LIFU neuromodulation has tremendous implications for noninvasive brain mapping and treating the human neurologic and psychiatric disease.

项目总结/摘要 神经调节，或大脑电路的操纵，已被证明是一个强大的工具， 神经科学和神经疾病的治疗。的当前方法 脑中的神经调节可能受到颅骨的限制， 或者由于空间分辨率不足。最近，超声技术已经发展， 声能可以通过完整的人类头骨精确地传递。我们的团队使用了 高强度聚焦超声（HIFU），通过 完整的头骨用于治疗人类的严重震颤。在这些经颅高强度聚焦超声中， 程序中，我们观察了丘脑腹外侧区的神经调制与临时 抑制震颤和感觉异常，但作用机制可能是热的。低 强度聚焦超声（LIFU）利用影响神经组织的不同特性 通过机械性能和没有热量或对大脑的损伤。 因此，我们假设低强度聚焦超声可以用于可逆的， 安全，精确的脑深部回路神经调节，使其成为一种理想的方式， 非侵入性脑成像为了证明这一假设，我们设计了一些实验， 将在大型脑猪模型中测试和优化LIFU神经调节。第一、 系统性调整输送至患者的脉压幅度或LIFU持续时间， 感觉丘脑将被用来区别地抑制或增强这些躯体感觉 通过诱发电位测量的通路。理论上，LIFU也可以靶向轴突， 像内囊中的皮质脊髓束这样的通路，而不是核靶点， 类似地操纵运动系统。 系统地优化皮层下神经调节的动物模型的开发是 独特.我们的初步结果已经抑制了大脑深部回路， 降低的体感诱发电位和LIFU能够映射感受野 丘脑的躯体感觉。我们还将能够探索不同的参数， 更短的持续时间和更多的爆发，这可能会激活神经组织或增加 SSEP。本项目将优化皮层下LIFU神经调制技术 并确认其安全性，以便在立体定向聚焦期间立即实施 超声波丘脑切开术。LIFU神经调节的相关性 对非侵入性脑映射和治疗人类神经系统和 精神病