Multiresolution FLIM and Reflectance Confocal Microscopy to Detect Dysplasia

描述（由申请人提供）：美国每年约有35，000名患者被诊断患有口腔癌，每年有7，500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，结合宽视场荧光寿命成像（FLIM）和反射共聚焦显微镜（RCM），以实现前所未有的灵敏度和特异性的上皮癌前病变在体内。亚细胞分辨率和相关的计算框架将能够解释所得到的图像，以产生基于生理，生化和形态学变化的诊断信息。本提案的具体目标是将由此产生的多分辨率FLIM-RCM系统应用于检测口腔癌前病变。 本研究的具体目标是：1）构建一个台式多分辨率FLIM-RCM系统，以展示FLIM-RCM表征正常、异型增生和癌变组织的能力; 2）设计和构建一个基于光纤的手持式FLIM-RCM探针，用于口腔癌前病变和癌症的体内成像; 3）优化FLIM-RCM用于口腔癌早期检测的灵敏度和特异性;以及4）证明FLIM-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光纤的多分辨率FLIM-RCM系统的组织表征的发展，并将展示其潜在的口腔癌前病变和恶性病变的非侵入性光学检测。这项新技术具有成为临床诊断和筛查工具的巨大潜力，是指导标准活检和手术干预的导航系统，也是定量评价当前和新型化学预防和治疗干预反应的工具。尽管该提议集中于口腔癌前病变的检测，但是所开发的成像系统和算法将通常适用于许多上皮癌（例如，子宫颈、结肠、直肠和膀胱）。 公共卫生相关性：在美国，每年约有35，000名患者被诊断患有口腔癌，并且每年有7，500名美国人死于这种疾病。诊断为口腔癌的患者的相对五年生存率从82%下降到27%，当检测到远处转移时，在局部早期发现。因此，早期发现至关重要。这项研究的目的是开发一种新的光学成像工具，以提高口腔癌前病变的早期检测。

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.