Development of a handheld probe for confocal microscopy and Raman spectroscopy*

描述（由申请人提供）：美国癌症协会建议，早期发现皮肤癌的最佳方法是通过定期自我检查来识别现有皮肤病变的变化或新病变的出现。一种便于对皮肤病变进行常规检查的方法是一种易于使用的、非侵入性的设备，它可以在相对较短的时间内扫描身体。这种装置可以通过普通医师办公室或皮肤科医生办公室使用。因此，提出了一种新的工具，提供空间，结构以及组织疾病状态的生化信息，最初针对皮肤癌的管理。本修订方案旨在开发一种手持式联合共聚焦拉曼光谱和共聚焦成像设备，可以提供皮肤病变的实时、形态学和生化信息，潜在地识别这些病变是正常的、良性的和恶性的，以诊断疾病。拉曼光谱是一种纯粹的生物化学技术，几乎不能提供有关组织微观结构的信息。共聚焦成像可以提供空间和结构信息，与共聚焦拉曼光谱一起可以产生有关组织结构和生物化学的信息，从而实现完整的诊断。因此，本研究的重点是开发一种具有共聚焦成像和明场成像能力的临床共聚焦拉曼仪器，通过提供实时、自动、非侵入性的光谱信息以及组织生物化学和结构的空间信息，用于皮肤病变的鉴别诊断。实施这一装置所需的步骤将独立进行。拟议项目的具体目标如下：具体目标(1)：开发和测试具有视频成像能力的紧凑型手持式拉曼探针。特定目标(2)开发和测试视频速率手持式共聚焦成像设备：特定目标(3)：开发和测试集成手持式共聚焦拉曼/扫描共聚焦成像手持设备。特异性目的(4)：检测体内正常和恶性皮肤组织的特征。具体目标(5)：了解在远离疾病区域的恶性组织中观察到的恶性肿瘤相关变化的基础和动态。本提案中计划的试点临床研究将在范德比尔特大学医学中心和范德比尔特诊所进行。拟议工作的发展将对卫生保健产生重大影响，因为它提供了利用单一紧凑、敏感的检测工具进行全面疾病管理的可能性。随着这项技术的成功，这种多模态仪器可以应用于其他器官部位，如前列腺和卵巢以及其他影响更广泛医学领域的疾病。

DESCRIPTION (provided by applicant): The American Cancer Society recommends that the best way to find skin cancers early is to recognize changes in existing skin lesions or the appearance of new lesions by regular self-examination. One way to facilitate this routine examination of skin lesions would be the availability of an easy-to-use, non-invasive device that can scan the body in a relatively short time. Such a device could be utilized through the general physician's office or the dermatologist's office. Thus a novel tool that provides spatial, structural as well as biochemical information about tissue disease state is proposed directed initially towards skin cancer management. This revised proposal seeks to develop a handheld combined confocal Raman spectroscopy and confocal imaging device that, can provide real-time, morphologic as well as biochemical information of skin lesions, potentially identifying these lesions as normal, benign and malignant for diagnosis of the disease. Raman spectroscopy is a purely biochemical technique and yields little information about the tissue microstructure. Confocal imaging could provide spatial as well as structural information that together with confocal Raman spectroscopy could yield information about tissue structure as well as biochemistry allowing for complete diagnosis. Thus this proposal is focused on the development of a clinical, confocal Raman instrument with confocal imaging as well as bright-field imaging capability for the differential diagnosis of skin lesions by providing real-time, automated, non-intrusive spectral as well as spatial information about the tissue biochemistry as well as structure. The steps needed to implement such a device will be pursued independently. The specific aims of the proposed project are as follows; Specific Aim (1): Develop and test a compact handheld Raman probe with video imaging capability. Specific Aim (2) Develop and test a handheld confocal imaging device at video rate: Specific Aim (3): Develop and test an integrated handheld confocal Raman/scanning confocal imaging handheld device. Specific Aim (4): Test signatures of normal and malignant skin tissues in vivo. Specific Aim (5): Understand the basis and dynamics of the malignancy associated changes observed in malignant tissues in regions away from the disease. The pilot clinical studies planned in this proposal will be conducted at the Vanderbilt University Medical Center and the Vanderbilt Clinic. The development of the proposed work will have a significant impact on health care by providing the potential for complete disease management with a single compact, sensitive detection tool. With the success of this technique, this multi-modal instrument can be applied to other organ sites such as the prostate and ovary as well as other diseases impacting a broader field in medicine.