Line-scanned MEMS-based dual-axis confocal microscopy to detect oral lesions in v

描述(申请人提供)：口腔癌是世界上第五大最常见的恶性肿瘤，在美国每年大约有50,000个新病例和超过10,000人死于这种疾病。耳鼻咽喉科医生接受过培训，以识别大体形态上表明恶性肿瘤的异常，并利用一些广域成像技术来提高病变的可视化，其中一些技术可以检测出灵敏度高但特异度低的疾病。由于诊断特异性差，当活检和组织病理学分析时，大多数可疑病变显示的是良性病变，而不是癌前病变或恶性病变。除了获取大量不必要的组织样本用于病理分析的高成本和高时间外，对侵入性活组织检查的需要通常会导致患者不适、不依从、并发症和/或诊断延误。反射共聚焦显微镜可以提供一种实时、非侵入性的方法来对切除活检进行分类和指导。然而，小型化是一个挑战，以前的体内系统需要在设备尺寸、成像速度(帧速率)、成像深度、分辨率和视场等关键参数之间进行权衡。该项目的目标是开发一种微型线扫描反射显微镜，首次将双轴共焦结构与基于MEMS的光束扫描相结合，以实现用于口腔病变实时微病理检测的优化临床设备。这是一台手持式电脑 尖端直径为2毫米的设备将使口腔组织深处的高对比度亚细胞成像成为可能。此外，还将实现高速(&gt；30赫兹)光学切片，这将大大提高该设备的临床可用性，因为它最大限度地减少了运动伪影和 实现高质量的实时图像拼接。蒙特卡罗散射模拟，以及对模体和组织标本的实验，将严格量化和优化线扫描双轴共焦显微镜的性能。最后，在这个技术开发项目的第三年，也就是最后一年，将进行临床可行性研究，以评估我们诊断原型的敏感性和特异性，并证明进一步的翻译工作是合理的。

DESCRIPTION (provided by applicant): Oral cancer is the fifth most common malignancy worldwide, with roughly 50,000 new cases and over 10,00 deaths from this disease each year in the United States. Otorhinolaryngologists are trained to recognize aberrations in gross morphology that are indicative of malignancy, as well as to utilize a number of wide-field imaging techniques to improve the visualization of lesions, some of which can detect disease with high sensitivity but poor specificity. As a result of poor diagnostic specificity, the majorit of suspected lesions, when biopsied and analyzed via histopathology, reveal benign conditions rather than premalignant or malignant lesions. In addition to the high costs and time associated with obtaining large numbers of unnecessary tissue samples for pathological analysis, the need for an invasive biopsy often results in patient discomfort, noncompliance, complications and/or diagnostic delays. Reflectance confocal microscopy can potentially provide a real-time non-invasive method to triage and guide excisional biopsy. However, miniaturization is a challenge and previous in vivo systems have necesitated trade-offs between critical parameters such as device size, imaging speed (frame rate), imaging depth, resolution, and field-of-view. The goal of this project is to develop a miniature line-scanned reflectance microscope that combines, for the first time, a dual-axis confocal architecture with MEMS-based beam scanning to achieve an optimized clinical device for real-time micropathological detection of oral lesions. This hand-held device, with a tip diameter of 2 mm, wil enable high-contrast sub-cellular imaging deep within tissues of the oral cavity. Furthermore, high- speed (>30 Hz) optical sectioning wil be achieved, which will greatly enhance the clinical usability of this device by minimizing motion artifacts and enabling high-quality real-time image mosaicing. Monte-Carlo scattering simulations, and experiments with phantoms and tissue specimens, will be performed to rigorously quantify and optimize the performance of line-scanned dual-axis confocal microscopy. Finally, in the third and final year of this technology-development project, a clinical feasibility study will be performed to assess the sensitivity and specificity of our diagnostic prototype and to justify further translational efforts.