Multiresolution FLIM and Reflectance Confocal Microscopy to Detect Dysplasia

描述（由申请人提供）：在美国，每年大约有35000名患者被诊断患有口腔癌，每年有7500名美国人死于这种疾病。本研究的长期目标是设计、构建和测试一种新型的多分辨率光纤内窥镜，该内窥镜结合了宽视场荧光寿命成像（FLIM）和反射共聚焦显微镜（RCM），以实现体内上皮癌前病变前所未有的灵敏度和特异性。亚细胞分辨率和相关的计算框架将能够解释产生的图像，从而产生基于生理、生化和形态变化的诊断信息。本提案的具体目标是应用所得到的多分辨率FLIM-RCM系统来检测口腔癌前病变。本提案的具体目的是：1)构建一个台式多分辨率flm - rcm系统，以证明flm - rcm表征正常、发育不良和癌组织的能力；2)设计并构建了一种基于纤维的手持式flm - rcm探针，用于口腔癌前和癌的体内成像；3)优化flm - rcm早期检测口腔癌的敏感性和特异性；4)证明了flm - rcm在体内检测上皮癌前病变的能力。这项工作的成功完成将使第一个基于纤维的多分辨率flm - rcm系统的发展成为可能，用于组织表征，并将证明其在口腔癌前病变和恶性病变的非侵入性光学检测方面的潜力。这项新技术具有巨大的潜力，可以成为临床诊断和筛查工具，指导标准活检和手术干预的导航系统，以及对当前和新的化学预防和治疗干预的反应进行定量评估的工具。虽然本提案的重点是口腔癌前病变的检测，但所开发的成像系统和算法将普遍适用于许多上皮癌（如宫颈癌、结肠癌、直肠癌和膀胱癌）。

DESCRIPTION (provided by applicant): Approximately 35,000 patients in the United States are diagnosed annually with cancer of the oral cavity, and 7,500 Americans die of this disease each year. The long-term goal of this research is to design, construct, and test a novel multiresolution fiber optic endoscope combining wide-field fluorescence lifetime imaging (FLIM) and reflectance confocal microscopy (RCM) to achieve unprecedented sensitivity and specificity of epithelial precancers in vivo. Subcellular resolution and the associated computational framework will enable interpretation of the resulting images to yield diagnostic information based on physiological, biochemical, and morphologic changes. The specific goal of this proposal is to apply the resulting multiresolution FLIM-RCM system to detect oral precancer. The specific aims of this proposal are to: 1) construct a bench-top multiresolution FLIM-RCM system to demonstrate the capability of FLIM-RCM to characterize normal, dysplastic, and cancerous tissue; 2) design and construct a fiber-based handheld FLIM-RCM probe for in vivo imaging of oral precancer and cancer; 3) optimize the sensitivity and specificity of FLIM-RCM for early detection of oral cancer; and 4) demonstrate the capability of FLIM-RCM to detect epithelial precancer in vivo. The successful completion of this work will enable the development of the first fiber-based multiresolution FLIM-RCM system for tissue characterization and will demonstrate its potential for non-invasive optical detection of oral premalignant and malignant lesions. This novel technology has significant potential to become a clinical diagnostic and screening tool, a navigation system for guiding standard biopsy and surgical intervention, and a tool for quantitative evaluation of responses to current and novel chemopreventive and therapeutic interventions. Although this proposal is focused on the detection of oral precancer, the imaging system and algorithms developed will be generally applicable to many of the cancers of the epithelium (e.g., cervix, colon, rectum, and bladder). PUBLIC HEALTH RELEVANCE: Approximately 35,000 patients in the United States are diagnosed annually with cancer of the oral cavity, and 7,500 Americans die of this disease each year. The relative five-year survival rate for patients diagnosed with oral cancer drops from 82% when detected early at the local stage to 27% when detected after distant metastasis. Early detection is thus critical. The goal of the proposed research is to develop a novel optical imaging tool to improve early detection of precancerous lesions in the oral cavity.