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

基于线扫描 MEMS 的双轴共焦显微镜可检测口腔病变

• 批准号: 8725638
• 负责人: Jonathan T.C. Liu
• 金额: $ 83.91万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725638
• 关键词: Architecture; Benign; Biopsy; Caliber; Cell Nucleus; Cessation of life; Clinic; Clinical; Clinical Research; Confocal Microscopy; Dermatology; Detection; Devices; Diagnosis; Diagnostic; Diagnostic Specificity; Disease; Engineering; Epithelium; Equilibrium; Excision biopsy; Feasibility Studies; Goals; Gold; Hand; Head and neck structure; Health; Histology; Histopathology; Human; Image; Imagery; Imaging Techniques; Imaging technology; Lesion; Malignant - descriptor; Malignant Neoplasms; Memorial Sloan-Kettering Cancer Center; Methods; Microscope; Microscopy; Miniaturization; Morphologic artifacts; Morphology; Motion; Optics; Oral cavity; Oral mucous membrane structure; Pathology; Patient Noncompliance; Patients; Performance; Premalignant; Preparation; Protocols documentation; Resolution; Sampling; Scanning; Screening for Oral Cancer; Sensitivity and Specificity; Site; Specificity; Specimen; Speed; System; Thick; Time; Tissue Sample; Tissues; Training; Triage; United States; base; cellular imaging; cohort; cost; economic implication; improved; in vivo; malignant mouth neoplasm; non-compliance; oral lesion; prototype; public health relevance; research study; simulation; technology development; tissue phantom; usability

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.

描述（由申请人提供）：口腔癌是全球第五大常见恶性肿瘤，在美国每年约有50，000例新发病例和10，000多例死亡。耳鼻喉科医生接受培训，以识别指示恶性肿瘤的大体形态学畸变，以及利用许多宽视野成像技术来改善病变的可视化，其中一些可以检测灵敏度高但特异性差的疾病。由于诊断特异性差，大多数可疑病变在活检和组织病理学分析时显示为良性病变，而不是癌前病变或恶性病变。除了与获得大量不必要的组织样本用于病理分析相关的高成本和时间之外，对侵入性活检的需要通常导致患者不适、不依从、并发症和/或诊断延迟。反射共聚焦显微镜可以潜在地提供一种实时非侵入性方法来分类和引导切除活检。然而，小型化是一个挑战，并且先前的体内系统已经在关键参数（诸如设备尺寸、成像速度（帧速率）、成像深度、分辨率和视场）之间进行了权衡。该项目的目标是开发一种微型线扫描反射显微镜，该显微镜首次将双轴共焦架构与基于MEMS的光束扫描相结合，以实现口腔病变实时显微病理检测的优化临床设备。这款手持 尖端直径为2 mm的设备将能够在口腔组织深处进行高对比度亚细胞成像。此外，将实现高速（>30 Hz）光学切片，这将通过最小化运动伪影而极大地增强该设备的临床可用性， 从而能够实现高质量的实时图像拼接。蒙特-卡罗散射模拟，并与幻影和组织标本的实验，将进行严格的量化和优化性能的线扫描双轴共焦显微镜。最后，在该技术开发项目的第三年也是最后一年，将进行临床可行性研究，以评估我们诊断原型的灵敏度和特异性，并证明进一步的转化工作是合理的。