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。一种促进皮肤病变的常规检查的方法是使用易于使用的非侵入性设备，该设备可以在相对较短的时间内扫描身体。这样的设备可以通过普通医生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，结构以及生物化学信息的组织疾病状态，最初针对皮肤癌的管理。该修订提案旨在开发一种手持式组合共焦拉曼光谱和共焦成像设备，该设备可以提供皮肤病变的实时、形态学以及生化信息，潜在地将这些病变识别为正常、良性和恶性以用于疾病的诊断。拉曼光谱是一种纯粹的生物化学技术，几乎没有关于组织微观结构的信息。共焦成像可以提供空间以及结构信息，与共焦拉曼光谱一起可以产生关于组织结构以及允许完整诊断的生物化学的信息。因此，该建议的重点是开发一种临床共焦拉曼仪器，该仪器具有共焦成像以及亮场成像能力，通过提供关于组织生物化学以及结构的实时、自动化、非侵入性光谱以及空间信息，用于皮肤病变的鉴别诊断。将独立采取实施这一装置所需的步骤。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拉曼探头。具体目标（2）开发和测试视频速率的手持式共焦成像设备：具体目标（3）：开发和测试集成的手持式共焦拉曼/扫描共焦成像手持式设备。具体目标（4）：体内正常和恶性皮肤组织的测试特征。具体目标（五）：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力学。本提案中计划的初步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，通过单一紧凑，灵敏的检测工具提供完整的疾病管理的潜力。随着这项技术的成功，这种多模式仪器可以应用于其他器官部位，如前列腺和卵巢，以及影响更广泛医学领域的其他疾病。

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.