Multiresolution FLIM and Reflectance Confocal Microscopy to Detect Dysplasia

多分辨率 FLIM 和反射共焦显微镜检测发育不良

• 批准号: 8504737
• 负责人: Kristen C. Maitland
• 金额: $ 27.72万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8504737
• 关键词: Algorithms; American; Animals; Area; Biochemical; Biopsy; Bladder; Cancerous; Cervix Uteri; Cheek structure; Chemopreventive Agent; Clinical; Colon; Computing Methodologies; Confocal Microscopy; Contrast Media; Databases; Detection; Development; Diagnosis; Diagnostic; Disease; Distant Metastasis; Drops; Dysplasia; Early Diagnosis; Endoscopes; Epithelial; Epithelium; Fiber; Fiber Optics; Fluorescence; Goals; Hamsters; Histopathology; Human; Image; Imaging Device; Imaging Techniques; Imaging technology; Individual; Lateral; Lesion; Malignant - descriptor; Malignant Neoplasms; Measurement; Metabolic; Microscopic; Microscopy; Modeling; Morphology; Navigation System; Normal tissue morphology; Operative Surgical Procedures; Optics; Oral; Oral cavity; Oral mucous membrane structure; Organ; Pathology; Patients; Physiological; Physiology; Premalignant; Quantitative Evaluations; Reading; Rectum; Relative (related person); Research; Resolution; Screening for Oral Cancer; Sensitivity and Specificity; Spectrum Analysis; Staging; Survival Rate; System; Technology; Testing; Therapeutic Intervention; Tissues; United States; Validation; Work; base; carcinogenesis; computer framework; design; design and construction; fluorophore; human tissue; imaging probe; improved; in vivo; instrument; malignant mouth neoplasm; miniaturize; new technology; novel; oncology; optical imaging; oral carcinogenesis; oral dysplasia; oral premalignancy; oral tissue; public health relevance; response; screening; spectroscopic imaging; tool; volunteer

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.

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。这项研究的长期目标是设计、构建和测试一种新型多分辨率光纤内窥镜，结合宽视场荧光寿命成像（FLIM）和反射共焦显微镜（RCM），以实现体内上皮癌前病变前所未有的敏感性和特异性。亚细胞分辨率和相关的计算框架将能够解释所得到的图像，以产生基于生理、生化和形态变化的诊断信息。该提案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。 该提案的具体目标是： 1）构建台式多分辨率 FLIM-RCM 系统，以证明 FLIM-RCM 表征正常、发育异常和癌组织的能力； 2）设计和构建基于光纤的手持式FLIM-RCM探头，用于口腔癌前病变和癌症的体内成像； 3）优化FLIM-RCM对口腔癌早期检测的敏感性和特异性； 4) 证明 FLIM-RCM 体内检测上皮癌前病变的能力。 这项工作的成功完成将有助于开发出第一个用于组织表征的基于光纤的多分辨率 FLIM-RCM 系统，并将展示其对口腔癌前病变和恶性病变进行非侵入性光学检测的潜力。这项新技术具有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定量评估当前和新型化学预防和治疗干预措施反应的工具的巨大潜力。尽管该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（例如子宫颈癌、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 名患者被诊断患有口腔癌，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局部早期检测时的 82% 下降到远处转移后检测时的 27%。因此，早期发现至关重要。拟议研究的目标是开发一种新型光学成像工具，以改善口腔癌前病变的早期检测。