Low Intensity Focused Ultrasound Neuromodulation

项目摘要/摘要 神经调节，或大脑回路的操纵，已被证明是一种强大的工具 神经科学和神经系统疾病的治疗。当前的方法 大脑中的神经调节可以受到颅骨的限制，侵入性地传递到深层结构 或者是由于空间分辨率不足。最近，超声波技术发展到了这样的地步 声波能量可以通过完整的人类头骨精确地传递。我们的团队已经使用了 高强度聚焦超声(HIFU)通过丘脑立体定向消融术 用于治疗人类严重震颤的完整头骨。在这些经颅HIFU治疗期间 手术中，我们观察了丘脑腹外侧部的神经调节 抑制震颤和感觉异常，但其作用机制可能是热的。低 强度聚焦超声(LIFU)利用不同的特性影响神经组织 通过机械性能，而且不会发热或对大脑造成损害。 因此，我们假设低强度聚焦超声可以用于可逆的， 安全、精确的大脑深部回路神经调节使其成为治疗 非侵入性脑图。为了证明这一假设，我们设计了一些实验， 利福神经调节将在大脑、猪模型中进行测试和优化。首先， 脉压幅度或力府持续时间的系统调整 感觉丘脑将被用来区别地抑制或增强这些躯体感觉 由诱发电位测量的通路。从理论上讲，理府也可以针对轴突 内囊中的皮质脊髓束等通路，而不是通往核靶的通路 同样地，操纵电机系统。 一种系统优化皮质下神经调节的动物模型的发展 独一无二。我们的初步结果抑制了大脑深层回路，这一点在瞬间得到了证明 降低的体感诱发电位和利福能够标测感受野 躯体感觉丘脑。我们还将能够探索不同的参数 持续时间更短，爆发率更高，这可能会激活神经元组织或增强 SSEP。这项在猪身上的项目将优化皮质下理府神经调节技术 并确认其安全性，以便在立体定向聚焦期间立即实施 人类的超音波丘脑切开术。理府神经调节的相关性有 无创脑标测和治疗人类神经学和神经病学的巨大意义 精神疾病。

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.