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.

本项目的目标是创建一种基于分瞳线扫描纤维束的共聚焦内窥镜，用于在体内对口腔黏膜的核和细胞形态进行反射对比成像，并在患者体内的临床研究中测试筛查口腔癌前病变和癌与正常组织的可行性。该内窥镜基于分瞳结构，可以克服现有基于光纤束和扫描单光纤共聚焦内窥镜的主要限制：来自光纤元件近端和远端面的强反向反射，从而在图像中产生强背景噪声。定量终点将根据灵敏度和特异性来确定，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。其动机是创建共聚焦内窥镜，用于实时无创反射成像，用于检测体内口腔癌前病变和术中定位，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。目视检查是常规检查，但在发现早期癌前病变或潜在癌性病变方面仍有不足。活组织检查和病理检查是目前的标准。然而，常规口腔活检既不可取也不实用。因此，患者在寻求和/或接受治疗时往往很晚，当癌症进展较晚时，生存率就低得多。共聚焦显微镜作为一种非侵入性的光学成像方式，可以显示病理样的细胞核和细胞细节，可以早期筛查癌前病变，同时减少活检的需要，减少疼痛和减少费用。在包括口腔在内的头颈部手术中，术中可以直接对患者进行测绘，以便对癌与正常组织的边缘进行充分和快速的检查，并指导术中准确和完整的切除，同时保留正常组织。分瞳线扫描共聚焦显微镜的初步结果显示，在体内，核和上皮细胞细节、更深的结缔组织和内唇-颊粘膜血流的反射成像非常好。光学切片为1.7 ？M，横向分辨率为1 ？M，与病理学相当。我们的假设是，使用两个光纤束的分瞳线扫描共聚焦内窥镜，一个用于照明，一个用于检测，可以克服最近开发的同轴光纤共聚焦内窥镜的强背反射的主要限制。分瞳结构可使成像在反射对比度。核和细胞在上皮、结缔组织和血流的细节可以在口腔内无创地观察，具有足够高的造影剂用于诊断和术中使用。该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定位，以指导皮肤、宫颈癌和乳腺癌的手术。