Novel Approach to Improve Port Wine Stain Treatment in Human Skin

描述(申请人提供)：鲜红斑点(PWS)是人类皮肤的一种血管畸形。目前，所有患者都使用单次冷冻剂喷雾(用于表皮保护)和单次激光脉冲照射(SCS-SLP)进行治疗。然而，PWS的反应仍然不可预测，只有不到10%的患者在SCS-SLP后PWS完全消退。PWS的治疗结果不充分是一个临床上重要的问题，需要解决。这项研究的中心假设是，多次激光脉冲(MLP)暴露间歇应用多次低温喷射器(MCS-MLP)不仅比SCS-SLP更安全，而且有望改善PWS的治疗结果。这项拟议的研究解决了PWS血管加热不足的一个关键障碍。虽然MCS将表皮温度维持在远低于损伤阈值的水平，但MLP的输送增加了核心血管内PWS血管内的温度，因为每次连续的激光脉冲都会在血管中显著积累热量。在历史上，用于PWS治疗的MLP包括提供一系列约1赫兹的激光脉冲。拟议的研究涉及将辐射曝光量低得多的MLP以高得多的重复率(~20赫兹)提供，并与MCS结合使用。建议的研究还采用图像引导治疗，以选择最佳的激光治疗参数的基础上个别患者的基础上，PWS病变的几何特征已通过红外断层扫描(IRT)。我们预计，使用MCS-MLP方法结合根据个别患者选择的治疗参数来治疗PWS将会改善漂白反应。在对PWS人皮肤进行的初步研究中，已经证明了MCS-MLP方法的可行性和潜在的应用前景，该方法可以在不损害上覆表皮的情况下破坏人皮肤下的PWS血管。本文提出的研究目标有望导致开发一种新的、高效果的治疗方法，作为解决长期无效的PWS治疗问题的解决方案。研究团队通过培训和经验具有很高的资格来实现这项建议的具体目标。该团队包括医用激光治疗(Nelson博士)、工程学(Svaasand和Jia博士)、物理学(Majaron博士)和生理学(Tan博士)方面的专业知识。 公共卫生相关性：目前对鲜红斑痣(PWS)胎记患者的临床管理方法是不够的。本文提出的研究目标是采用多次激光脉冲(MLP)暴露间歇应用多次低温喷射法(MCS-MLP)，以开发一种新的、高影响力的治疗方法，作为长期无效治疗PWS的解决方案。这样的结果将有助于NIH从根本上改进疾病治疗的方法学发展使命。

DESCRIPTION (provided by applicant): Port wine stain (PWS) is a vascular malformation of human skin. Presently, all patients are treated using a single cryogen spurt (for epidermal protection) and single laser pulse exposure (SCS-SLP). However, PWS response remains unpredictable with less than 10% of patients achieving complete fading of their PWS after SCS-SLP. Inadequate PWS therapeutic outcome is a clinically significant problem that requires a solution. The central hypothesis of the proposed research is that multiple cryogen spurts (MCS) applied intermittently with multiple laser pulse (MLP) exposures (MCS-MLP) is not only safer than SCS- SLP but also expected to improve PWS therapeutic outcome. The proposed research addresses a critical barrier of inadequate PWS blood vessel heating. While MCS maintain the epidermal temperature well below the damage threshold, delivery of MLP increases the core intravascular PWS blood vessel temperature because of significant heat accumulation in the vessels with each successive laser pulse. Historically, MLP for PWS treatment involved the delivery of a series of laser pulses on the order of 1 Hz. The proposed research involves using MLP of much lower radiant exposure delivered at much higher repetition rates (~20 Hz) in combination with MCS. The proposed research also employs image-guided therapy to select the optimal laser treatment parameters on an individual patient basis after PWS lesion geometry has been characterized by infrared tomography (IRT). We expect that PWS treated using the MCS-MLP approach in conjunction with treatment parameters selected on an individual patient basis will have improved blanching responses. In preliminary studies conducted on PWS human skin, the feasibility and potential application of the MCS-MLP approach to cause destruction of subsurface PWS blood vessels in human skin, without damaging the overlying epidermis, has been demonstrated. The objective of the studies proposed herein is expected to lead to the development of a novel, high impact therapeutic approach as a solution for the long-standing problem of ineffective treatment of PWS. The research team is highly qualified by training and experience to accomplish the specific aims of this proposal. The team comprises expertise in medical laser therapy (Dr. Nelson), engineering (Drs. Svaasand and Jia), physics (Dr. Majaron) and physiology (Dr. Tan). PUBLIC HEALTH RELEVANCE: The current approach to the clinical management of patients with port wine stain (PWS) birthmarks is inadequate. The objective of the studies proposed herein using multiple cryogen spurts (MCS) applied intermittently with multiple laser pulse (MLP) exposures (MCS-MLP) is expected to lead to the development of a novel, high impact therapeutic approach as a solution for the long-standing problem of ineffective treatment of PWS. Such an outcome will contribute to the NIH mission of methodology development to improve fundamentally the treatment of disease.