CPS: Functional Feedback Methods for Wearable Focused Ultrasound Therapy

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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).