Fiber bundle-based divided-pupil confocal endoscope

基于光纤束的分瞳共焦内窥镜

• 批准号: 8122281
• 负责人: MILIND RAJADHYAKSHA
• 金额: $ 56.84万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-06 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8122281
• 关键词: Alcohol consumption; American Cancer Society; Area; Back; Basal cell carcinoma; Benign; Biopsy; Blood flow; Cancerous; Cellular Morphology; Cessation of life; Cheek structure; Clinic; Clinical; Clinical Research; Confocal Microscopy; Connective Tissue; Country; Dermatologic; Detection; Development; Diagnosis; Diagnostic; Distal; Elements; Endoscopes; Engineering; Epithelium; Excision; Face; Fiber; Goals; Hand; Head and Neck Cancer; Head and Neck Surgery; Hour; Human Papillomavirus; Image; Incidence; India; Inflammatory; Iron; Lamina Propria; Lateral; Lesion; Light; Lighting; Lip structure; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Maps; Microscope; Modification; Mohs Surgery; Molecular; Motivation; Noise; Normal tissue morphology; Nuclear; Oncogenic Viruses; Operative Surgical Procedures; Optics; Oral cavity; Oral mucous membrane structure; Pain; Pathology; Patients; Performance; Premalignant; Primary Neoplasm; Pupil; Radiation; Radiation therapy; Reporting; Resolution; Risk; Scanning; Screening procedure; Sensitivity and Specificity; Skin Cancer; Smoker; Smoking; Squamous cell carcinoma; Staging; Surgeon; Survival Rate; Syphilis; Technology; Testing; Time; Tissues; Tongue; Translating; Tumor Suppressor Genes; Visual; Work; World Health Organization; advanced disease; base; clinically relevant; cost; design; human subject; human tissue; imaging modality; imaging probe; improved; in vivo; instrument; instrumentation; light scattering; malignant breast neoplasm; malignant mouth neoplasm; melanoma; optical imaging; oral lesion; oral premalignancy; prototype

The goal of this project is to create a divided-pupil line-scanning fiber bundle-based confocal endoscope for imaging nuclear and cellular morphology in oral mucosa in vivo with reflectance contrast, and to test feasibility for screening oral precancers and cancers versus normal tissue in a clinical study on patients in vivo. The endoscope is based on a divided-pupil configuration that may overcome the major limitation of existing fiber bundle-based and scanned single fiber-based confocal endoscopes: strong back-reflections from the proximal and distal faces of the fiber element, which produces strong background noise in the images. Quantitative endpoints will be determined in terms of sensitivity and specificity to validate the feasibility of the technology and justify further development toward clinical utility. The motivation is to create confocal endoscopes for real-time noninvasive imaging in reflectance for detection of oral precancers in vivo and intra-operative mapping to guide surgery of head-and-neck cancers. Oral cancer is the fifth most common malignancy in the world. Visual examination is routinely performed but remains deficient in detecting early-stage precancers or potentially cancerous lesions. Biopsy and pathology are the current standard. However, routine biopsies in the oral cavity are neither desirable nor practical. Consequently, patients are often seriously late in seeking and/or receiving treatment and the survival rate is much lower when the cancer is more advanced. Confocal microscopy, as a noninvasive optical imaging modality that shows pathology-like nuclear and cellular detail, may enable early screening of precancers, while minimizing the need for biopsy, minimizing pain and minimizing expense. During head-and-neck surgery which includes the oral cavity, intra-operative mapping may be possible directly on the patient, to enable adequate and rapid examination of cancer-to-normal tissue margins and to guide accurate and complete excision during surgery, while preserving normal tissue. Preliminary results with a divided-pupil line-scanning confocal microscope demonstrate excellent imaging in reflectance of nuclear and cellular detail in the epithelium, deeper connective tissue and blood flow in the inside lip-buccal mucosa in vivo. The optical sectioning is 1.7 ?m and lateral resolution is 1 ?m, which is comparable to that of pathology. Our hypothesis is that a divided-pupil line-scanning confocal endoscope with the use of two fiber bundles, one for illumination and one for detection, may overcome the major limitation of strong back-reflections in recently developed coaxial fiber-based confocal endoscopes. The divided-pupil configuration may enable imaging in reflectance contrast. Nuclear and cellular detail in the epithelium, connective tissue and blood flow may be noninvasively visualized in the oral cavity in vivo with sufficiently high contrast for diagnostic as well as for intra-operative use. The proposed technology may have broad clinical impact with long-term applications in detection in vivo and intra-operative mapping to guide surgery of skin, cervical and breast cancers.

该项目的目标是创建一种基于分瞳线扫描光纤束的共焦内窥镜，用于通过反射对比对体内口腔粘膜的核和细胞形态进行成像，并在对患者体内的临床研究中测试筛查口腔癌前病变和癌症与正常组织的可行性。该内窥镜基于分瞳配置，可以克服现有基于光纤束和基于扫描单光纤的共焦内窥镜的主要限制：来自光纤元件的近端面和远端面的强烈背反射，从而在图像中产生强烈的背景噪声。定量终点将根据敏感性和特异性来确定，以验证该技术的可行性并证明进一步开发临床应用的合理性。其动机是创建用于实时无创反射成像的共焦内窥镜，以检测体内口腔癌前病变，并在术中绘图以指导头颈癌的手术。口腔癌是世界上第五大常见恶性肿瘤。目视检查是常规进行的，但在检测早期癌前病变或潜在癌性病变方面仍然存在缺陷。活检和病理学是当前的标准。然而，常规口腔活检既不理想也不实用。因此，患者在寻求和/或接受治疗时往往严重迟到，并且当癌症处于晚期时，生存率要低得多。共聚焦显微镜作为一种非侵入性光学成像方式，可以显示类似病理学的核和细胞细节，可以实现癌前病变的早期筛查，同时最大限度地减少活检的需要，最大限度地减少疼痛和费用。在包括口腔在内的头颈手术期间，可以直接在患者身上进行术中标测，以便能够充分、快速地检查癌症与正常组织的边缘，并在手术过程中指导准确、完整的切除，同时保留正常组织。分瞳线扫描共聚焦显微镜的初步结果表明，在体内上皮细胞核和细胞细节、更深的结缔组织和内部唇颊粘膜的血流方面具有出色的成像效果。光学切片为1.7μm，横向分辨率为1μm，与病理分辨率相当。我们的假设是，使用两根光纤束（一根用于照明，一根用于检测）的分瞳线扫描共焦内窥镜可以克服最近开发的基于同轴光纤的共焦内窥镜中强背反射的主要限制。分开的瞳孔配置可以实现反射对比度成像。上皮、结缔组织和血流中的核和细胞细节可以在口腔中以非侵入性方式在体内可视化，具有足够高的对比度以用于诊断以及术中使用。所提出的技术可能具有广泛的临床影响，可长期应用于体内检测和术中绘图，以指导皮肤癌、宫颈癌和乳腺癌的手术。