CPS: Functional Feedback Methods for Wearable Focused Ultrasound Therapy

聚焦超声（FUS）是一种多用途的治疗方式，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，从而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，其中低强度超声导致周围神经放电速率和模式的非侵入性和空间/时间精确变化，可能是由于组织加热和离子通道机械激活的结合。超声神经调节有前景的临床应用包括治疗膀胱过度活动综合征（OAB），这在约23%的美国人口中很普遍，也包括慢性疼痛。这些应用需要慢性和患者特异性治疗才能获得长期健康益处，这反过来又建议使用可穿戴和自主的FUS设备。然而，实现这样的设备面临着几个基本的挑战，包括1)在定位错误和内部组织/器官运动存在的情况下，安全、精确地将FUS治疗递送到特定的身体目标（在这种情况下，是神经）；ii)确定神经调节参数（频率、重复率、波形、功率水平）的最佳值，这些参数预计既具有患者特异性（由于生物异质性），又具有时间依赖性。在本提案中，一个跨学科团队将通过开拓可穿戴FUS神经调节的闭环方法来解决这些挑战。

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).