Structured illumination multispectral fluorescence lifetime microendoscopy to detect oral premalignancies

结构照明多光谱荧光寿命显微内窥镜检测口腔癌前病变

• 批准号: 8976837
• 负责人: Bilal Malik
• 金额: $ 7.43万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-02 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8976837
• 关键词: Accounting; American; American Cancer Society; Basal Cell; Benign; Biochemical; Biological; Biological Markers; Carcinoma; Cervical; Characteristics; Cheek structure; Collagen; Collection; Colorectal; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Drops; Early identification; Endoscopes; Endoscopy; Epithelial; Epithelium; Evaluation; Exhibits; Family suidae; Fluorescence; Generations; Goals; Hamsters; Health; Image; Imaging Techniques; In Vitro; Keratin; Lamina Propria; Lesion; Light; Lighting; Malignant - descriptor; Malignant Neoplasms; Metabolic; Modeling; Modification; Molecular; NADH; Optics; Oral; Oral Examination; Oral cavity; Outcome; Patients; Performance; Pharyngeal structure; Physiological; Porphyrins; Premalignant; Process; Reporting; Research; Screening for Oral Cancer; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Speed; Squamous cell carcinoma; Staging; Structural Genes; Structure; Survival Rate; System; Techniques; Testing; Three-Dimensional Image; Tissue imaging; Tissues; United States; Work; adaptive optics; attenuation; base; carcinogenesis; cofactor; design; fluorophore; imaging system; improved; in vivo; instrument; intraepithelial; liquid crystal; malignant mouth neoplasm; molecular marker; optical imaging; oral carcinogenesis; oral lesion; oral premalignancy; screening; tissue phantom

 DESCRIPTION (provided by applicant): The American Cancer Society estimates that more than 40,000 new cases of invasive cancer in the oral cavity and pharynx are reported each year in the US, and five-year survival rates remain below 40% for advanced stage disease. The goal of this research is to design, build and test a structured illumination-enabled multispectral widefield fluorescence lifetime imaging microendoscope for detection of oral precancer in vivo. Combining structured illumination (SI) with fluorescence lifetime imaging (FLIM) would enable generation of high fidelity three dimensional volumes of the fluorescence intensity and lifetime of the epithelial tissue. We believe that the ability to collect 'optical sections' across the epithelum would allow characterization of tissue biochemical composition due to differential distribution of molecular markers, such as structural proteins and metabolic cofactors, within tissue and will ultimately aid in high sensitivity and specificity detection of early oral cancer development. The specific aims of this proposal are to: 1) construct a structured illumination multispectral FLIM endoscope (SI-FLIM) system to provide optical depth sectioning; 2) characterize the performance and optimize the design specifications of the SI-FLIM endoscope by imaging in vitro and ex vivo; and 3) validate and demonstrate the capability of SI-FLIM by imaging tissue in vivo. The successful completion of this work will enable the development of the first multispectral SI-FLIM microendoscope with the ability to selectively image specific depths within the tissue, and will demonstrate its potential for non-invasive characterization of oral premalignant and malignant lesions. With the wealth of specific molecular information encoded in the collected fluorescence intensity and lifetime in multiple spectral channels, such a device can serve to provide an objective screening of the oral cavity in addition to the clinician's subjective evaluation. Although the proposed endoscope is designed for application of this device in the oral cavity, the SI-FLIM system can be applicable to detect and diagnose other carcinomas (e.g. basal cell, colorectal, and cervical) as well with slight modifications to the endoscope.

 描述（由申请人提供）：美国癌症协会估计，美国每年报告超过 40,000 例口腔和咽部浸润性癌症新病例，晚期疾病的五年生存率仍低于 40%。这项研究的目标是设计、构建和测试一种支持结构化照明的多光谱宽场荧光寿命成像显微内窥镜，用于结合结构化照明来检测体内口腔前体。 （SI）与荧光寿命成像（FLIM）将能够生成荧光强度和寿命的高保真度三维体积 我们相信，通过上皮收集“光学切片”的能力将允许由于组织内分子标记（例如结构蛋白和代谢辅助因子）的差异分布来表征组织生化成分，并最终有助于提高灵敏度。该提案的具体目标是：1）构建结构化照明多光谱 FLIM 内窥镜（SI-FLIM）系统以提供光学深度切片；2）表征性能并优化；通过体外和离体成像确定 SI-FLIM 内窥镜的设计规范；3）通过体内组织成像验证和证明 SI-FLIM 的能力。这项工作的成功完成将使第一个多光谱 SI 的开发成为可能。 -FLIM 显微内窥镜能够选择性地对组织内的特定深度进行成像，并将通过收集的荧光强度和寿命中编码的丰富的特定分子信息展示其对口腔癌前病变和恶性病变进行非侵入性表征的潜力。在多个光谱通道中，除了临床医生的主观评估之外，这种装置还可以提供口腔的客观筛查。尽管所提出的内窥镜是为该装置在口腔中的应用而设计的，但是SI-FLIM系统可以适用于检测和诊断其他癌症（例如基底细胞癌、结直肠癌和宫颈癌），并对内窥镜稍加修改。

项目成果

Volumetric structured illumination microscopy enabled by a tunable-focus lens.

• DOI: 10.1364/ol.40.004943
• 发表时间: 2015-11-01
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: Hinsdale T;Malik BH;Olsovsky C;Jo JA;Maitland KC
• 通讯作者: Maitland KC

Objective Detection of Oral Carcinoma with Multispectral Fluorescence Lifetime Imaging In Vivo.

• DOI: 10.1111/php.12627
• 发表时间: 2016-09
• 期刊: Photochemistry and photobiology
• 影响因子: 3.3
• 作者: Malik BH;Lee J;Cheng S;Cuenca R;Jabbour JM;Cheng YS;Wright JM;Ahmed B;Maitland KC;Jo JA
• 通讯作者: Jo JA