Acousto-optic Theragnostic Approach for Chronic Wound Management

描述（由申请人提供）：我们提出的计划的长期目标是开发一种非侵入性慢性伤口治疗，以协同的方式结合光学和声学模式。这种治疗诊断（theragnostic），即治疗（peutic）和诊断（dia）诊断技术，将非侵入性超声治疗与近红外（NIR）诊断监测相结合，将允许伤口护理提供者通过“Band-Aid（R）”状可穿戴贴片规定低频超声治疗，利用数字成像和NIR评估伤口愈合的状态，并根据需要调整超声参数。这里考虑的治疗涉及将伤口暴露于非侵入性低频（20-100 kHz）超声能量，并定期实时数字和近红外（NIR）监测与伤口愈合参数相关的组织光学特性。因此，由光学传感器提供的体内获取的诊断信息将与治疗相结合，并用于指导和优化伤口愈合治疗。我们的最终目标是开发一种无菌的、患者友好的贴片，该贴片包含超声施加器和相关的电子控制器，可以由患者直接应用于伤口。这种可穿戴贴片将允许频繁（每天或甚至每天多次暴露）应用超声治疗，而无需患者返回诊所，并将显著提高患者对治疗的依从性。为了实现这一目标，我们将建立最佳的超声暴露参数，这将作为原型“创可贴（R）"样的可穿戴超声施加器的基础。我们方法的新奇包括使用无创、安全水平的低频超声治疗，通过独特开发的低成本可穿戴超声施加器实现伤口愈合的无创光学诊断。这种系统的方法将通过对人类静脉溃疡的研究进行验证，提供目前无法获得的定量信息。我们的基本假设是，低频超声可以为慢性伤口提供有效的治疗，并且可以通过NIR监测评估伤口愈合来优化这种治疗的应用。因此，我们的具体目标是：具体目标1：开发超声辅助慢性伤口愈合的最佳暴露矩阵方案。确定最佳超声“低”频率（20或100 kHz），并评估总能量密度对伤口愈合的影响。伤口愈合通过NIR和伤口尺寸测定来评估。具体目标二：根据特定目标1的结果，开发并测试基于慢性伤口超声施加器的“创可贴（R）"式可穿戴超声贴片装置的早期原型。具体目标3：使用特定目标2中开发的超声施加器原型，确定（惯性和稳定）空化和机械应力作为可能机制的可能作用，并排除热效应。具体目标4：在特定目标1中确定的最佳条件下，在人类患者中植入“Band-Aid（R）"状可穿戴超声贴片原型。在这项研究完成后，将建立最佳的暴露矩阵，并将构建和测试可穿戴慢性伤口敷料器的早期原型。该项目的结果还将为影响伤口愈合的可能机制提供见解。 公共卫生相关性：慢性伤口，包括静脉性腿部溃疡、压疮、缺血性溃疡和糖尿病足溃疡，是当今老龄化社会的重要问题。在美国，有超过400万患者患有这些类型的伤口，每年的治疗费用为90亿美元。所提出的治疗诊断技术将可穿戴非侵入性低频超声治疗与近红外诊断监测相结合，可以产生定制的治疗模式，该治疗模式具有以低成本提供个性化有效治疗的潜力。

DESCRIPTION (provided by applicant): The long-term objective of our proposed program is to develop a non-invasive chronic wound treatment that combines optic and acoustic modalities in a synergistic way. This theragnostic, i.e. thera(peutic) and (dia)gnostic technology, merging a non-invasive ultrasound therapy with Near Infrared (NIR) diagnostic monitoring, will allow a wound care provider to prescribe low frequency ultrasound therapy through a "Band-Aid(R)"-like wearable patch, assess the status of wound healing with digital imaging and NIR, and adjust the ultrasound parameters as necessary. The treatment considered here involves exposure of the wound to non-invasive low (20-100 kHz) frequency ultrasound energy with periodic real-time digital and near infrared (NIR) monitoring of tissue optical properties related to wound healing parameters. Thus, in vivo acquired diagnostic information provided by an optic sensor will be combined with therapy and used to direct and optimize wound healing treatment. Our ultimate goal is to develop a sterile, patient friendly patch containing an ultrasound applicator and associated electronic controls that could be directly applied by a patient to the wound. This wearable patch will allow for frequent (daily or even multiple exposures per day) application of the ultrasound therapy without a return of the patient to the clinic and will significantly increase patient compliance with the therapy. In order to accomplish this goal, we will establish the optimal ultrasound exposure parameters that will serve as the basis for the prototype "Band-Aid(R)"-like wearable ultrasound applicator. The novelty of our approach consists of using non-invasive, safe levels of low frequency ultrasound therapy with non-invasive optical diagnosis of wound healing enabled through the unique development of a low-cost wearable ultrasound applicator. This systematic approach will be validated through a study of venous ulcers in humans, providing quantitative information not available currently. Our underlying hypothesis is that low frequency ultrasound can provide an effective therapy for chronic wounds and that application of this therapy can be optimized by assessment of wound healing through NIR monitoring. Accordingly, our specific aims are: Specific Aim 1: Develop optimal exposure matrix protocol for ultrasonically assisted chronic wound healing. Identify optimal ultrasound "low" frequency (20 or 100kHz) and assess effect of total energy density on wound healing. Wound healing is assessed by NIR and wound size determination. Specific Aim 2: Based on the outcomes of Specific Aim 1, develop and test an early prototype of the "Band-Aid(R)"-like wearable ultrasound patch device based chronic wound ultrasound applicator. Specific Aim 3: Using the prototype of the ultrasound applicator developed in Specific Aim 2 identify the possible role of (inertial and stable) cavitation and mechanical stresses as possible mechanisms, and rule out thermal effects. Specific Aim 4: Validate the "Band-Aid(R)"-like wearable ultrasound patch prototype in human patients under the optimal conditions identified in Specific Aim 1. At the completion of this research, the optimum exposure matrix will be established and an early prototype of the wearable chronic wound applicator will be constructed and tested. The results of this project will also provide insights into the possible mechanisms affecting wound healing. PUBLIC HEALTH RELEVANCE: Chronic wounds, which include venous leg ulcers, pressure sores, ischemic ulcers, and diabetic foot ulcers, are a significant problem in today's aging society. In the United States there are over 4 million patients afflicted with these types of wounds, with an annual treatment cost of 9 billion dollars. The proposed theragnostic technology, merging wearable non-invasive low frequency ultrasound therapy with near infrared diagnostic monitoring, can result in a customized treatment modality which has the potential to deliver individualized effective therapy at low cost.