Acousto-optic Theragnostic Approach for Chronic Wound Management

描述(由申请人提供)：我们建议的计划的长期目标是开发一种非侵入性的慢性伤口治疗，以协同的方式结合视觉和听觉模式。这种将非侵入性超声治疗与近红外(NIR)诊断监测相结合的非侵入性超声治疗技术，即Thera(Peutic)和(Dia)nnotics技术，将使伤口护理提供者能够通过类似“创可贴(R)”的可穿戴贴片开出低频超声波治疗处方，使用数字成像和近红外技术评估伤口愈合状况，并根据需要调整超声参数。这里考虑的治疗包括将伤口暴露在非侵入性低频率(20-100 kHz)超声能量下，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，其中包含一个超声波敷贴器和相关的电子控制装置，患者可以直接将其应用于伤口。这种可穿戴的贴片将允许患者在不返回临床的情况下频繁地(每天或甚至每天多次曝光)应用超声波治疗，并将显著提高患者对治疗的依从性。为了实现这一目标，我们将确定最优的超声暴露参数，这些参数将作为类似于“创可贴(R)”的可穿戴超声照射器原型的基础。我们方法的新颖性包括使用非侵入性、安全水平的低频超声治疗，并通过开发一种低成本可穿戴式超声波敷贴器实现伤口愈合的非侵入性光学诊断。这种系统化的方法将通过对人类静脉性溃疡的研究来验证，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一种有效的治疗方法，通过近红外监测对伤口愈合进行评估，可以优化这种疗法的应用。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基质方案。确定最佳的超声“低”频率(20或100 kHz)，并评估总能量密度对伤口愈合的影响。伤口愈合通过近红外光谱和伤口大小测定来评估。特定目标2：基于特定目标1的结果，开发并测试基于慢性创面超声敷贴器的类似“创可贴(R)”的可穿戴超声贴片装置的早期原型。具体目标3：利用在具体目标2中开发的超声波喷射器的原型，确定(惯性和稳定的)空化和机械应力作为可能的机制的可能作用，并排除热效应。具体目标4：在特定目标1确定的最佳条件下，在人类患者身上验证类似“创可贴(R)”的可穿戴超声贴片原型。在这项研究完成时，将建立最佳暴露矩阵，并将建造和测试可穿戴慢性伤口敷贴器的早期原型。该项目的结果还将为影响伤口愈合的可能机制提供深入的见解。

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.