CPS: Functional Feedback Methods for Wearable Focused Ultrasound Therapy

聚焦超声(FUS)是一种多功能的治疗方式，它提供了一种非侵入性的方式，将目标声能沉积在体内深处，导致通过热和非热机制与组织和器官发生复杂的相互作用。一个有趣的例子是神经调节，在这种情况下，低强度超声波导致周围神经的放电频率和模式发生非侵入性的、空间/时间上精确的变化，这可能是由于组织加热和离子通道的机械激活的共同作用。超声神经调节的潜在临床应用包括治疗膀胱过度活动症(OAB)，该综合征在美国约23%的人口中普遍存在，还包括慢性疼痛。这些应用需要长期和针对患者的治疗才能获得长期的健康益处，这反过来又建议使用可穿戴和自动FUS设备。然而，实现这种设备面临几个基本挑战，包括i)在存在定位错误和内部组织/器官运动的情况下，安全和准确地向特定的身体靶点(在这种情况下，是神经)提供FUS治疗；以及ii)确定神经调制参数(频率、重复率、波形、功率水平)的最佳值，这些参数预计是患者特定的(由于生物异质性)和时间依赖的。在这项提案中，一个跨学科团队将通过开创可穿戴FUS神经调节的闭环方法来应对这些挑战。 拟议的项目将通过追求以下具体目标实现闭环可穿戴超声治疗：(1)可穿戴和身体共形超声阵列，(2)多维信号处理，(3)主动传感，和(4)多模式反馈。PI和共同IS拥有互补的专业知识，并将展示将这些跨学科目标紧密整合到一个单一框架中的优势。我们相信，由此产生的结果可能会改变用于调节周围神经系统的非侵入性设备的研究和设计。此外，我们的工作有望在物联网支持的传感平台(灵活的和身体共形超声成像和神经调制)、物理驱动的数据处理和分析(时空Delta-Sigma算法、主动扫描)和实时控制(发现最佳神经调制参数)方面取得根本性进展。

Focused ultrasound (FUS) is a versatile therapeutic modality that offers a non-invasive way to deposit targeted acoustic energy deep in the body, resulting in complex interactions with tissues and organs that occur through both thermal and non-thermal mechanisms. An interesting example is neuromodulation, in which low-intensity ultrasound results in noninvasive and spatially/temporally precise changes in the firing rates and patterns of peripheral nerves, likely due to a combination of both tissue heating and mechanical activation of ion channels. Promising clinical applications for ultrasound neuromodulation include treatment of overactive bladder syndrome (OAB), which is prevalent in ~23% of the U.S. population, and also chronic pain. These applications require chronic and patient-specific treatment to obtain long-term health benefits, which in turn suggests the use of wearable and autonomous FUS devices. However, realizing such devices faces several fundamental challenges, including i) safe and precise delivery of FUS therapy to a specific body target (in this case, a nerve) in the presence of positoning errors and internal tissue/organ motion; and ii) determining optimal values for the neuromodulation parameters (frequency, repetition rate, waveform, power level), which are expected to be both patient-specific (due to biological heterogeneity) and time-dependent. In this proposal, an interdisciplinary team will address these challenges by pioneering a closed-loop approach to wearable FUS neuromodulation. The proposed project will enable closed-loop wearable ultrasound therapy by pursuing the following specific aims: (1) wearable and body-conformal ultrasound arrays, (2) multi-dimensional signal processing, (3) active sensing, and (4) multimodal feedback. The PI and co-Is have complementary expertise and will demonstrate the strengths of tightly integrating these interdisciplinary aims into a single framework. We believe the resulting outcomes could transform the research and design of non-invasive devices for modulating the peripheral nervous system. In addition, our work is expected to achieve fundamental advances in IoT-enabled sensing platforms (flexible and body-conformal ultrasound imaging and neuromodulation), physics-driven data processing and analytics (spatio-temporal Delta-Sigma algorithms, active scanning), and real-time control (discovery of optimum neuromodulation parameters).