Acousto-optic Theragnostic Approach for Chronic Wound Management

慢性伤口处理的声光治疗诊断方法

• 批准号: 8464100
• 负责人: Peter A. Lewin
• 金额: $ 36.52万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464100
• 关键词: Acoustics; Affect; Aging; Animal Model; Animals; Care given by nurses; Caring; Cell membrane; Chronic; Clinic; Clinical; Combined Modality Therapy; Computers; Decubitus ulcer; Development; Devices; Diabetic Foot Ulcer; Diagnosis; Diagnostic; Electronics; Evaluation; Fiber; Frequencies; Goals; Guidelines; Healed; Health Personnel; Hospitals; Human; Investigation; Left; Leg Ulcer; Measurement; Measures; Mechanical Stress; Methodology; Methods; Modality; Molecular; Monitor; Optics; Outcome; Outpatients; Patients; Physicians; Property; Protocols documentation; Provider; Radiation; Reporting; Research; Role; Societies; Sterility; Stream; Structure; System; Technology; Testing; Time; TimeLine; Tissues; Transducers; Treatment Cost; Ulcer; Ultrasonic Therapy; Ultrasonography; United States; Variant; Varicose Ulcer; Venous; Visit; Visual impairment; Work; Wound Healing; absorption; base; compliance behavior; cost; design; digital; digital imaging; effective therapy; energy density; healing; human study; human subject; in vitro testing; in vivo; insight; laptop; miniaturize; programs; prototype; public health relevance; research study; sensor; wound

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.

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的慢性伤口治疗，以协同的方式结合了视觉和声学方式。 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.此处考虑的处理涉及伤口接触到非侵入性低（20-100 kHz）频率超声能量，并定期实时数字和近红外（NIR）监测与伤口愈合参数有关的组织光学特性。因此，由光学传感器提供的体内获得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个无菌，患者友好的补丁，其中包含超声涂抹器和相关的电子控件，该贴片可以由患者直接应用于伤口。这种可穿戴的贴片将允许在无需病人返回诊所的情况下频繁地（每天甚至每天多次暴露）应用超声治疗，并且会大大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曝光参数，这些参数将作为原型“ band-aid（r）”的基础 - 像可穿戴的超声涂抹器一样。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疗法，并通过独特的低成本可穿戴超声涂抹器的独特开发来实现伤口愈合的非侵入性光学诊断。这种系统的方法将通过对人类的静脉溃疡的研究来验证，提供当前无法使用的定量信息。我们的基本假设是，低频超声可以为慢性伤口提供有效的疗法，并且可以通过通过NIR监测评估伤口愈合来优化这种疗法。因此，我们的具体目的是：特定目标1：为超声辅助慢性伤口愈合制定最佳暴露矩阵方案。确定最佳的超声“低”频率（20或100kHz），并评估总能量密度对伤口愈合的影响。伤口愈合通过NIR和伤口大小的确定评估。特定目标2：基于特定目标1的结果，开发和测试“创可贴（R）”的早期原型，例如可穿戴超声贴片装置的慢性伤口超声涂抹器。特定目标3：使用特定目标中开发的超声施加器的原型2确定（惯性和稳定）气蚀和机械应力的可能作用作为可能的机制，并排除了热效应。特定目标4：验证“创可贴（R）” - 像在特定目标1中确定的最佳条件下的人类患者的可穿戴超声贴片原型一样。在这项研究完成后，将建立最佳暴露矩阵，并将构建和测试可穿戴的慢性伤口涂抹器的早期原型。该项目的结果还将提供有关影响伤口愈合的可能机制的见解。

项目成果

Effects of Non-thermal, Non-cavitational Ultrasound Exposure on Human Diabetic Ulcer Healing and Inflammatory Gene Expression in a Pilot Study.

• DOI: 10.1016/j.ultrasmedbio.2018.05.011
• 发表时间: 2018-09
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Bajpai A;Nadkarni S;Neidrauer M;Weingarten MS;Lewin PA;Spiller KL
• 通讯作者: Spiller KL

Development of Low Frequency (20-100 kHz) Clinically Viable Ultrasound Applicator for Chronic Wound Treatment.

• DOI: 10.1109/tuffc.2018.2836311
• 发表时间: 2019-03
• 期刊: IEEE transactions on ultrasonics, ferroelectrics, and frequency control
• 作者: Ngo O;Niemann E;Gunasekaran V;Sankar P;Putterman M;Lafontant A;Nadkarni S;DiMaria-Ghalili RA;Neidrauer M;Zubkov L;Weingarten M;Margolis DJ;Lewin PA
• 通讯作者: Lewin PA

Enhanced therapeutic anti-inflammatory effect of betamethasone on topical administration with low-frequency, low-intensity (20 kHz, 100 mW/cm(2)) ultrasound exposure on carrageenan-induced arthritis in a mouse model.

在小鼠模型中，通过低频、低强度（20 kHz，100 mW/cm(2)）超声照射，增强倍他米松局部给药对角叉菜胶诱导的关节炎的治疗抗炎作用。

• DOI: 10.1016/j.ultrasmedbio.2015.04.009
• 发表时间: 2015
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Cohen,Gadi;Natsheh,Hiba;Sunny,Youhan;Bawiec,ChristopherR;Touitou,Elka;Lerman,MelissaA;Lazarovici,Philip;Lewin,PeterA
• 通讯作者: Lewin,PeterA

Optimization of un-tethered, low voltage, 20-100kHz flexural transducers for biomedical ultrasonics applications.

• DOI: 10.1016/j.ultras.2012.03.004
• 发表时间: 2012-09
• 期刊: ULTRASONICS
• 影响因子: 4.2
• 作者: Sunny, Youhan;Bawiec, Christopher R.;Nguyen, An T.;Samuels, Joshua A.;Weingarten, Michael S.;Zubkov, Leonid A.;Lewin, Peter A.
• 通讯作者: Lewin, Peter A.

Finite element static displacement optimization of 20-100 kHz flexural transducers for fully portable ultrasound applicator.

• DOI: 10.1016/j.ultras.2012.09.005
• 发表时间: 2013-02
• 期刊: ULTRASONICS
• 影响因子: 4.2
• 作者: Bawiec, Christopher R.;Sunny, Youhan;Nguyen, An T.;Samuels, Joshua A.;Weingarten, Michael S.;Zubkov, Leonid A.;Lewin, Peter A.
• 通讯作者: Lewin, Peter A.