Multiresolution FLIM and Reflectance Confocal Microscopy to Detect Dysplasia

描述(申请人提供)：美国每年约有35,000名患者被诊断为口腔癌，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、建造和测试一种新型的多分辨率光纤内窥镜，该内窥镜结合了广域荧光寿命成像(FLIM)和反射共聚焦显微镜(RCM)，以获得体内前所未有的上皮癌前病变的敏感性和特异性。亚细胞分辨率和相关的计算框架将能够解释产生的图像，以产生基于生理、生化和形态变化的诊断信息。这项提议的具体目标是应用由此产生的多分辨率Flim-RCM系统来检测口腔癌前病变。该建议的具体目的是：1)构建台式多分辨率Flim-RCM系统，以展示FLIM-RCM对正常组织、异型增生组织和癌组织的特征；2)设计和构建用于口腔癌前病变和癌组织活体成像的光纤手持Flim-RCM探针；3)优化FLIM-RCM早期检测口腔癌的敏感性和特异性；以及4)展示FLIM-RCM在活体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系统的开发成为可能，并将展示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。这项新技术具有成为临床诊断和筛查工具的巨大潜力，成为指导标准活检和手术干预的导航系统，以及定量评估对当前和新的化学预防和治疗干预措施的反应的工具。虽然这项建议侧重于口腔癌前病变的检测，但开发的成像系统和算法将普遍适用于许多上皮癌(例如，宫颈癌、结肠癌、直肠癌和膀胱癌)。 公共卫生相关性：美国每年约有35,000名患者被诊断为口腔癌，每年有7,500名美国人死于这种疾病。被诊断为口腔癌的患者的相对五年生存率从局部早期发现的82%下降到远处转移后发现的27%。因此，及早发现至关重要。这项研究的目标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.