Confocal Raman Microspectrometer for Cancer Detection

描述(申请人提供)：在本方案中，提出了在紧凑型仪器中设计、组装和测试双分辨率图像导引共焦拉曼显微光谱仪。拟议的系统将由一个手持探头组成，能够提供三种模式的信息。(1)彩色视频成像-将提供大体组织成像(约5 mm x 5 mm)，因此将指导选择需要近距离观察的感兴趣区域，(2)亮场共焦显微镜-将提供所选区域(约300微米x 300微米)中心的细胞水平的深度分辨率形态图谱，单点分辨率为0.75微米，(3)拉曼显微光谱学-将提供所选区域(与共焦相同)的深度分辨率生化评估，分辨率约为5-10微米，将在R21阶段根据信噪比进行优化。手持探头将与光谱仪和探测器配置相耦合，可以在用于临床和研究调查的紧凑型仪器中编译、处理和显示组织表征所需的所有信息。本文提出的仪器将被优化为以实时、非侵入性的方式检测早期皮肤癌作为诊断和手术指导工具。拟议项目可行性阶段(R21)的具体目标如下：(1)设计和制造台式HIRM探头和仪器。(2)体外表征皮肤组织的罗马特征并评估其在体测量的可行性(3)评估构建微型HIRM装置所需的参数(4)根据AIM(3)确定的规格设计微型HIRM探头和系统。这些目标一旦实现，将显示拟议工作的可行性，确定规格，从而产生一种商业上可行的、临床上有用的手持图像引导共焦拉曼显微光谱仪的设计，优化皮肤癌检测。一旦设计完成，探测器和系统将在提案的R33阶段构建和测试。TILE提案开发阶段的具体目标如下：(1)使用组织模体和体外皮肤样本建立和测试手持探针和仪器，调试系统和改进设计，(2)使用台式探针表征30名皮肤癌患者和30名正常志愿者的体内皮肤拉曼光谱，(3)使用共聚焦拉曼光谱仪评估活体组织切片中发现差异的基础。(4)将最终的手持式探头原型用于30名患者的活体皮肤组织研究，(5)开发区分各种类型的恶性和非恶性皮肤组织的诊断算法。拟议工作的发展将对医疗保健产生重大影响，因为它提供了使用单一紧凑、灵敏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，拉曼光谱可以应用于其他器官部位，如前列腺和卵巢以及其他疾病，从而影响到更广泛的医学领域。

DESCRIPTION (provided by applicant): In this proposal, the design, assembly and testing of a dual resolution image-guided confocal Raman microspectrometer in a compact instrument is proposed. The proposed system will consist of a handheld probe capable of providing three modes of information. (1) Color video imaging - will provide gross tissue imaging ( about 5mm x 5mm) and thus will guide the selection of interesting areas that require a closer look, (2) Bright-field confocal microscopy - will provide depth resolved morphological mapping from the center of the selected region ( about 300 mu m x 300 mu m) at a cellular level with a single point resolution of 0.75 mu m and (3) Raman microspectroscopy - will provide depth resolved biochemical evaluation of the selected region (same as confocal) with a resolution around 5-10 mu m to be optimized in the R21 phase based on signal to noise. The handheld probe will be coupled to a spectrometer and detector configuration that can compile, process and display all information required for tissue characterization in a compact instrument for clinical use as well research investigation. The instrument proposed here will be optimized for the detection of early skin cancer in a real-time, non-invasive manner as a diagnostic as well as surgical guidance tool.The specific aims of the feasibility phase (R21) of the proposed project are as follows; (1) Design and build a bench-top HIRM probe and instrument,. (2) Characterize Roman signatures of skin tissues in vitro and assess the feasibility of measuring it in vivo (3) Evaluate the parameters necessary to build a miniature HIRM device (4) Design the miniature HIRM probe and system based on the specifications determined in Aim (3). These objectives when achieved will show feasibility of the proposed work, determine the specifications and thus yield a design of a commercially viable, clinical useful handheld image-guided confocal Raman microspectrometer optimized for skin cancer detection.Once designed, the probe and system will be constructed and tested in the R33 phase of the proposal. The specific aims of the development phase of tile proposal are as follows; (1) Build and test the handheld probe and instrument using tissue phantoms and in vitro skin samples, debug system and modify design, (2) Characterize in vivo skin Raman spectra using the bench-top probe on 30 skin cancer patients and 30 normal volunteers, (3) Evaluate the basis for the differences seen in live tissue sections using the confocal Raman microspectrometer. (4) Use the final handheld probe prototype for skin tissue studies in vivo in 30 patients, (5) Develop diagnostic algorithms that distinguish between the various types of malignant and non-malignant skin tissues.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, Raman spectroscopy can be applied to other organ sites such as the prostate and ovary as well as other diseases thus impacting a broader field in medicine.