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）： 葡萄酒色斑（PWS）是人类皮肤的一种血管畸形。目前，所有患者均使用单次冷冻剂喷射（用于表皮保护）和单次激光脉冲照射（SCS-SLP）进行治疗。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 治疗结果不足是一个需要解决的临床重大问题。拟议研究的中心假设是，间歇性应用多次冷冻剂喷射 (MCS) 和多次激光脉冲 (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 保持表皮温度远低于损伤阈值，但 MLP 的输送会增加核心血管内 PWS 血管温度，因为每个连续激光脉冲都会在血管中积聚大量热量。从历史上看，用于 PWS 治疗的 MLP 涉及传输一系列 1 Hz 量级的激光脉冲。拟议的研究涉及将 MLP 与 MCS 结合使用，以更高的重复率（~20 Hz）提供更低的辐射暴露。该研究还采用图像引导治疗，在通过红外断层扫描 (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来治疗 PWS 将改善漂白反应。在对 PWS 人体皮肤进行的初步研究中，已经证明了 MCS-MLP 方法破坏人体皮肤表面下 PWS 血管而不损伤上覆表皮的可行性和潜在应用。本文提出的研究目标预计将导致开发一种新颖的、高效的治疗方法，作为长期存在的 PWS 治疗无效问题的解决方案。该研究团队经过培训和经验丰富，资质优良，能够完成本提案的具体目标。该团队由医学激光治疗（Nelson 博士）、工程学（Svaasand 和 Jia 博士）、物理学（Majaron 博士）和生理学（Tan 博士）方面的专业知识组成。 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还不够充分。本文提出的研究目标是使用间歇性应用多次冷冻剂喷射 (MCS) 和多次激光脉冲 (MLP) 照射 (MCS-MLP)，预计将导致开发一种新颖的、高影响力的治疗方法，作为长期治疗的解决方案。 -PWS治疗效果不佳的长期问题。这样的成果将有助于 NIH 开发方法论的使命，从根本上改善疾病的治疗。