Novel Approach to Improve Port Wine Stain Treatment in Human Skin

改善人类皮肤波特酒色斑治疗的新方法

• 批准号: 8042421
• 负责人: JOHN STUART NELSON
• 金额: $ 30.81万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-07 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8042421
• 关键词: Address; Animal Model; Animals; Blood; Blood Vessels; Clinical Management; Clinical Research; Clinical Trials; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Dose; Engineering; Epidermis; Heating; Human; Image; Individual; Lasers; Lead; Lesion; Light; Light Coagulation; Link; Low-Level Laser Therapy; Medical; Methodology; Mission; Modeling; Optics; Outcome; Overdose; Patients; Phase; Physics; Physiologic pulse; Physiology; Port-Wine Stain; Principal Investigator; Property; Qualifying; Research; Risk; Rodent; Safety; Series; Skin; Solutions; Study Section; Temperature; Therapeutic; Training; Treatment Efficacy; United States National Institutes of Health; Work; base; clinically significant; experience; image guided therapy; improved; innovation; malformation; novel; novel strategies; public health relevance; response; standard care; tomography

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.

描述（由申请人提供）：港口葡萄酒染色（PWS）是人类皮肤的血管畸形。目前，所有患者均使用单个低温器（用于表皮保护）和单个激光脉冲暴露（SCS-SLP）进行治疗。但是，PWS反应仍然无法预测，不到10％的患者在SCS-SLP之后实现了其PWS的完全褪色。 PWS治疗结果不足是一个需要解决方案的临床意义问题。拟议的研究的中心假设是，多个低温基因（MCS）用多个激光脉冲（MLP）暴露（MCS-MLP）间歇性地应用不仅比SCS-SLP更安全，而且预计将改善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。尽管MC将表皮温度远低于损伤阈值，但MLP的递送会增加核心血管内PWS血管血管温度，这是由于每个连续的激光脉冲在血管中大量积聚。从历史上看，PWS治疗的MLP涉及以1 Hz的速度传递一系列激光脉冲。拟议的研究涉及使用以更高的重复率（约20 Hz）和MC结合使用的MLP较低的辐射暴露。拟议的研究还采用图像引导的治疗来在PWS病变几何形状以红外层析成像（IRT）为特征后，以个别患者的基础选择最佳的激光治疗参数。我们预计，使用MCS-MLP方法处理的PW与在单个患者基础上选择的治疗参数结合使用将有改善的平淡反应。在对PWS人体皮肤进行的初步研究中，MCS-MLP方法的可行性和潜在应用导致人体皮肤中地下PWS血管破坏，而没有损害上覆的表皮。预计本文提出的研究的目的有望导致一种新型，高影响的治疗方法的发展，以解决长期存在PWS治疗的长期问题。研究团队通过培训和经验来实现该建议的具体目标，因此具有很高的资格。该团队包括医疗激光治疗（纳尔逊博士），工程学（Svaasand和Jia博士），物理学（Majaron博士）和生理学（TAN博士）。 公共卫生相关性：当前对港口葡萄酒染色（PWS）胎记患者临床管理的方法不足。本文提出的研究使用多个低温基因（MCS）用多个激光脉冲（MLP）暴露（MCS-MLP）进行间歇性应用的目的，预计将导致开发一种新型的，高影响的治疗方法作为解决PWS无效治疗的长期解决问题的解决方案。这样的结果将有助于NIH方法发展的使命，从而从根本上改善疾病的治疗。