Novel Approach to Improve Port Wine Stain Treatment in Human Skin

描述（由申请人提供）： 鲜红斑痣是一种皮肤血管畸形。目前，所有患者都使用单次冷冻剂喷射（用于表皮保护）和单次激光脉冲曝光（SCS-SLP）进行治疗。然而，PWS反应仍然是不可预测的，在SCS-SLP后，不到10%的患者实现了PWS的完全消退。PWS治疗结果不充分是一个需要解决的临床重要问题。所提出的研究的中心假设是，间歇性应用多次冷冻剂喷射（MCS）与多次激光脉冲（MLP）暴露（MCS-MLP）不仅比SCS-SLP更安全，而且预计还可改善PWS治疗结果。拟议的研究解决了PWS血管加热不足的关键障碍。虽然MCS维持表皮温度远低于损伤阈值，但输送MLP会增加核心血管内PWS血管温度，因为每个连续激光脉冲都会在血管中产生显著的热积聚。在历史上，用于PWS治疗的MLP涉及以1 Hz的量级递送一系列激光脉冲。拟议的研究涉及使用MLP的低得多的辐射暴露，在高得多的重复率（~20 Hz）与MCS相结合。拟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后，PWS病变的几何形状已被红外断层扫描（IRT）的特点，在个别患者的基础上。我们预计，使用MCS-MLP方法结合根据个体患者选择的治疗参数治疗的PWS将改善漂白反应。在对PWS人类皮肤进行的初步研究中，已经证明了MCS-MLP方法在人类皮肤中引起皮下PWS血管破坏而不损伤上覆表皮的可行性和潜在应用。本文提出的研究的目的预计将导致开发一种新的，高影响力的治疗方法，作为PWS治疗无效的长期问题的解决方案。研究团队经过培训和经验丰富，能够完成本提案的具体目标。该团队包括医学激光治疗（纳尔逊博士）、工程（Svaasand和Jia博士）、物理（Majaron博士）和生理学（Tan博士）方面的专业知识。 公共卫生相关性： 目前的临床管理方法与港口葡萄酒色斑（PWS）胎记患者是不够的。本文提出的使用多次冷冻剂喷射（MCS）间歇地施加多次激光脉冲（MLP）暴露（MCS-MLP）的研究的目的预期导致开发一种新型的、高影响的治疗方法，作为PWS的长期无效治疗问题的解决方案。这样的结果将有助于国家卫生研究院的方法学发展的使命，从根本上改善疾病的治疗。

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.