Two photon fluorescence microscopy for dermatologic surgery and biopsy

联邦医疗保险每年报销500多万例活检，导致150万例外科手术 非黑素瘤皮肤癌(NMSC)。尽管它给医疗保健系统带来了负担，但治疗仍然是时间- 由于用于诊断和指导治疗的组织学方法效率低下，消耗性和可获得性不均衡。 作为替代，双光子荧光显微镜(TPFM)与快速分子标记相结合 可以比传统方法更快地评估组织学。我们已经开发了高速TPFM 皮肤科外科成像，人体组织快速分子标记方案，并进行 初步研究表明，TPFM可以评估皮肤癌，其准确性与传统方法相似 组织学。我们的方法解决了当前方法的局限性，这些方法从诊断开始，其中 组织学检查的延误意味着，如果活组织检查呈阳性，患者必须再次前往诊所就诊。效率低下 在治疗过程中被复合，在标准的切除中，处理的延迟意味着组织学上的 术后评估，可能需要二次手术才能完成治疗。或者，在Mohs 手术时，可以使用术中冰冻切片，从而大大增加手术时间和 诊所容量减少。其结果是，费用增加，获得护理的机会受到区域差异的影响， 农村地区的患者更有可能接受不合格的护理，使他们面临毁容或肿瘤的风险 复发。这项研究计划的目标是推进外科手术的双光子成像技术 应用，然后进行临床试验，测试TPFM在两种诊断活检中的使用 神经间充质干细胞的手术方式和治疗。这项提议的目标是：目标1将发展改进 TPFM结合了探测器和激光技术的最新进展，以降低成本、缩小尺寸和 增强对比度，为NMSC的诊断和治疗提供了有效的新工具。同时，研究将 检查TPFM对一种不太常见的皮肤癌类型的准确性。AIM 2将研究接受治疗的患者 皮肤病活检，测试使用TPFM可以立即诊断患者的假设，使 常见皮肤癌的就诊治疗相同。最后，目标3建议进行介入手术试验。目标3，任务 1将把TPFM整合到Mohs手术中，测试更快的组织成像可以加速这一假设 治疗。目标3，任务2将在标准(非Mohs)皮肤切除中引入用于边缘评估的TPFM 癌症，测试在术中没有成像的情况下可以使用TPFM的假设 目前是实用的。总的来说，这些目标将测试更有效的诊断和切除皮肤的方法 癌症、加速治疗、降低成本和发病率，同时扩大获得护理的机会。成功 该项目的完成将展示普通外科病理学的强大新工具，并验证 用于皮肤科手术。

Medicare reimburses over 5 million biopsies resulting in 1.5 million surgical procedures annually for nonmelanoma skin cancer (NMSC). Despite its burden on the health care system, treatment remains time- consuming and unevenly available due to inefficient histologic methods used for diagnosis and to guide therapy. As an alternative, two photon fluorescence microscopy (TPFM) combined with rapid molecular labeling can evaluate histology dramatically faster than conventional methods. We have developed high speed TPFM imaging for dermatologic surgery, protocols for rapid molecular labeling of human tissue, and conducted preliminary studies showing that TPFM can evaluate skin cancer with similar accuracy to conventional histology. Our approach addresses the limitations of current methods, which begin with diagnosis, where the delay for histology means that patients must return for a second clinic visit if biopsies are positive. Inefficiencies are compounded during therapy, where in standard excision the delay for processing means that histology is evaluated postoperatively, and a second surgery may be required to complete therapy. Alternatively, in Mohs surgery, intraoperative frozen sections may be used, resulting in a substantial increase in procedure time and reduced clinic capacity. As a result, costs are increased and access to care is subject to regional variations, with patients in rural areas more likely to receive substandard care that puts them at risk for disfigurement or tumor recurrence. The goal of this research program is to advance two photon imaging technology for surgical applications, and then conduct clinical trials testing the use of TPFM in both diagnostic biopsy procedures and in surgical treatment of NMSC. The aims for this proposal are: Aim 1 will develop improved TPFM that incorporates recent advances in detector and laser technology to reduce cost, shrink size, and enhance contrast, providing an efficient new tool for diagnosing and treating NMSC. Concurrently, studies will examine the accuracy of TPFM for a less common type of skin cancer. Aim 2 will study patients undergoing dermatologic biopsy, testing the hypothesis that patients can be immediately diagnosed using TPFM, enabling same visit treatment for common skin cancers. Finally, Aim 3 proposes interventional surgical trials. Aim 3, Task 1 will integrate TPFM into Mohs surgery, testing the hypothesis that faster histological imaging can accelerate treatment. Aim 3, Task 2 will introduce TPFM for margin evaluation into standard (non-Mohs) excision of skin cancer, testing the hypothesis that TPFM can be used in a scenario for which no intraoperative imaging is currently practical. Collectively, these aims will test more efficient methods of diagnosing and excising skin cancer, accelerating treatment, reducing costs and morbidity while expanding access to care. Successful completion of this project would demonstrate powerful new tools for general surgical pathology and validate them for use in dermatologic surgery.