Novel Approach to Improve Port Wine Stain Treatment in Human Skin

描述（由申请人提供）：葡萄酒色斑（PWS）是一种人体皮肤血管畸形。目前，所有患者均采用单次低温喷射（用于表皮保护）和单次激光脉冲暴露（SCS-SLP）治疗。然而，PWS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治疗效果不足是一个需要解决的临床重大问题。本研究的中心假设是，间歇性地使用多次冷喷（MCS）与多次激光脉冲（MLP）照射（MCS-MLP）不仅比SCS- SLP更安全，而且有望改善PWS的治疗效果。提出的研究解决了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MLP的传递增加了核心血管内PWS血管温度，因为每个连续的激光脉冲在血管中积累了大量的热量。从历史上看，用于PWS治疗的MLP涉及一系列1hz数量级的激光脉冲的传递。拟议的研究包括使用以更高的重复频率（~20 Hz）提供更低辐射暴露的MLP与MCS相结合。该研究还采用图像引导治疗，在红外断层扫描（IRT）表征PWS病变几何形状后，根据患者个体选择最佳激光治疗参数。我们预计，使用MCS-MLP方法结合根据患者个体选择的治疗参数治疗PWS将改善白化反应。在对PWS人体皮肤进行的初步研究中，已经证明了MCS-MLP方法在不损伤上覆表皮的情况下破坏人体皮肤中PWS皮下血管的可行性和潜在应用。本文提出的研究目标有望导致一种新的、高影响的治疗方法的发展，以解决长期存在的PWS治疗无效的问题。该研究小组在训练和经验方面都是非常合格的，可以完成这项建议的具体目标。该团队包括医学激光治疗（Nelson博士），工程（Dr. Nelson博士）。物理学（Majaron博士）和生理学（谭博士）。

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.