CRCNS: Crossbeam Transcranial Ultrasound Technology to Stimulate the Deep Brain

摘要 无创神经调节技术存在大量神经科学和临床应用， 可以以高分辨率到达大脑深处。一项引人注目的临床应用是药物治疗 成瘾是美国的一个重大公共卫生挑战。在人类中，治疗的神经目标是 1-4 mm3，因此一个关键目标是以比目前更高的分辨率刺激大脑深处 与任何无创刺激方式。本研究的目标是开发和实验 高分辨率深脑经颅超声优化计算模型的验证 刺激（TUS）用于神经科学和临床应用。无创经颅超声刺激 已在各种动物模型中显示出安全性和空间特异性。然而，当前的系统是 未针对深部大脑的高分辨率 TUS 进行优化。计算模型表明我们可以优化 具有相控阵系统的 TUS，可以成对驱动，同时彼此成 90° 定向并聚焦 到同一点，称为“横梁”。这将刺激分辨率提高了一个数量级以上 幅度。此外，我们的模型表明我们可以使用 “捏”或“拉伸”。在这个项目中，我们将对 Crossbeam 的改进进行生物学验证 由于神经组织对“收缩”或“拉伸”的敏感性而产生的有效性。我们经过验证的模型将是 用于完善涉及优化阵列探针的横梁神经刺激策略。这将不允许 不仅可以选择焦深，还可以补偿传播引起的相位像差 穿过颅骨。优化的硬件和开发的计算模型将被集成 具有成像引导并在头骨模型实验中得到验证。 相关性（参见说明）： 我们正在开发通过神经系统疾病的无创治疗来改善健康的技术 诸如成瘾之类的疾病。

SUMMARY Numerous neuroscience and clinical applications exist for a noninvasive neuromodulation technology that can reach deep in the brain with high resolution. One compelling clinical application is the treatment of drug addiction, a major public health challenge in the US. In humans, the neural targets for treatment are 1-4 mm3, and thus a critical goal is to stimulate deep in the brain with higher resolutions than currently available with any noninvasive stimulation modality. The goal of this research is the development and experimental validation of computational models for optimization of high resolution deep brain transcranial ultrasound stimulation (TUS) for neuroscience and clinical application. Noninvasive transcranial ultrasound stimulation has been shown to be safe and spatially specific in various animal models. However, current systems are not optimized for high resolution TUS of the deep brain. Computational modeling suggests we can optimize TUS with phased array systems that can be driven in pairs while oriented at 90° to each other and focused to the same point, called “crossbeam.” This improves the stimulation resolution by more than an order of magnitude. In addition, our modeling suggests that we can selectively stimulate neural tissue using a “pinch” or “stretch.” In this project, we will perform a biological validation of crossbeam’s improved effectiveness due to the neural tissue’s sensitivity to “pinch” or “stretch.” Our validated modeling will be used to refine a crossbeam neurostimulation strategy involving optimized array probes. This will allow not only choice of focal depth, but also compensation of phase aberrations resulting from the propagation through the skull bone. The optimized hardware and the developed computational models will be integrated with imaging guidance and validated in skull phantom experiments. RELEVANCE (See instructions): We are developing the technology for improving health through the noninvasive treatment of neurological disorders such as addiction.