A New Integrated Endoscope System

描述（由申请人提供）：一个新的集成内窥镜系统项目概述本提案是一个合作的、多团队的、多学科的项目，涉及来自华盛顿大学生物工程、电气工程、机械工程、医学和病理学部门的研究人员。目的是开发和验证新一代扫描光纤内窥镜和分子造影剂，以改善腔内器官癌症的早期检测。该内窥镜将基于先进的微机电系统（MEMS）技术，通过提供快速二维光栅光束扫描和动态焦点跟踪，同时保持小直径（d3 mm），克服了当前扫描内窥镜的局限性。两种具有互补优势的微型扫描仪技术，每一种都旨在实现其内窥镜应用技术类别中的最佳性能，将通过该计划进行开发。为了适应快速变化环境下的大面积成像，将研制一种具有宽扫描角的高速悬臂波导扫描仪。将开发一种具有主动焦点跟踪的微镜扫描仪，用于高分辨率三维成像。这两种技术的演示为未来在单一内窥镜通道中集成这两种功能开辟了一条道路。提议的内窥镜将实现实时三维成像和高分辨率光学成像技术的功能集成，包括光学相干断层扫描（OCT）和共聚焦荧光内窥镜。分子造影剂将基于荧光标记的纳米颗粒，显示针对发育不良和早期癌细胞的肽配体。本课题旨在通过克服以下挑战来推进当前内镜技术的发展：(1)内镜光束扫描技术，实现均匀可控的扫描模式和三维成像能力；(2)在不同成像深度下保持高分辨率；(3)探头小型化；(4)正常组织与癌前或癌早期之间的内在差异较弱；(5)对早期癌症缺乏分子特异性。靶向空间分辨率（< 5.5 m）和三维成像能力将显著提高我们目前有限的早期和癌前检测能力。本项目的具体目标是：1。研制一种小型化波导悬臂式扫描仪，具有快速光束扫描（谐振频率> 20 kHz）和宽视场（>60 kHz），可实现大面积实时成像。2. 开发高分辨率（< 5.5 m）和动态焦点跟踪（1mm深度范围）的可变形MEMS扫描微镜和光学封装，实现高质量的三维成像。3. 评价扫描内窥镜对正常和早期肿瘤的高分辨率OCT和共聚焦荧光成像在仓鼠颊袋癌模型中的表现。4. 探讨用新鲜人食管切除术标本加或不加分子造影剂，用扫描探针检测高级别不典型增生和粘膜内癌的可行性。公共卫生相关性：本提案的目的是开发和验证新一代扫描光纤内窥镜和分子造影剂，以改善腔内器官癌症的早期检测。该内窥镜将基于先进的微机电系统（MEMS）技术，通过提供快速二维光栅光束扫描和动态焦点跟踪，同时保持小直径（d3 mm），克服了当前扫描内窥镜的局限性。提议的内窥镜将实现实时三维成像和高分辨率光学成像技术的功能集成，包括光学相干断层扫描（OCT）和共聚焦荧光内窥镜。分子造影剂将基于荧光标记的纳米颗粒，显示针对发育不良和早期癌细胞的肽配体。扫描内窥镜出色的空间分辨率（< 5.5 m）和三维成像能力，以及提供增强对比度的癌症靶向纳米颗粒，将显著提高我们目前有限的早期和癌前检测能力。PHS 398/2590（09/04修订版，4/2006修订版）第1页延续格式页

DESCRIPTION (provided by applicant): A New Integrated Endoscope System Project Summary This proposal is a collaborative, multi-team, and multidisciplinary program involving investigators from the Departments of Bioengineering, Electrical Engineering, Mechanical Engineering, Medicine, and Pathology at the University of Washington. The objective is to develop and validate a new generation of scanning fiber-optic endoscopes and molecular contrast agents for improving early detection of cancer in luminal organs. The endoscope will be based on advanced micro-electro-mechanical systems (MEMS) technologies, overcoming limitations in current scanning endoscopes by offering fast 2-dimensional raster beam scanning and dynamic focus tracking while maintaining a small diameter (d3 mm). Two micro-scanner technologies with complementary advantages, each aiming to achieve the best performance in its category of technology for endoscope applications, will be developed through this program. A high-speed cantilever waveguide scanner with wide scanning angle will be developed for large-area imaging in fast-changing environment. A micro- mirror scanner with active focus tracking will be developed for high-resolution 3-D imaging. Demonstration of both technologies opens a route to integration of both capabilities in a single endoscope channel in the future. The proposed endoscope will enable real-time 3-D imaging and functional integration of high-resolution optical imaging techniques including optical coherence tomography (OCT) and confocal fluorescence endomicroscopy. The molecular contrast agents will be based upon fluorescently-labeled nanoparticles that display peptide ligands targeting dysplasia and early cancer cells. This proposal aims to advance the current endoscopy technology by overcoming the following challenges: (1) endoscopic beam scanning technology for achieving a uniform, controllable scanning pattern and 3-dismentional imaging capability; (2) maintaining high resolution over various imaging depths; (3) probe miniaturization; (4) the weak intrinsic contrast between normal tissue and pre- or early cancers; and (5) the lack of molecular specificity to early cancers. The targeted spatial resolution (<5 5m) and 3-dimensional imaging capability will significantly improve our currently limited ability for detecting early and pre-cancers. The specific aims of this project are: 1. Develop a miniaturized waveguide cantilever scanner capable of rapid beam scanning (> 20 kHz resonant frequency) with wide field of view (>60:) for real-time imaging of large area. 2. Develop deformable MEMS scanning micro-mirror and optical packaging with high resolution (<5 5m) and dynamic focus-tracking (1 mm depth range) for high-quality 3-dimensional imaging. 3. Evaluate the performance of the scanning endoscope for high resolution OCT and confocal fluorescence imaging of normal and early cancer in an in-vivo hamster cheek pouch cancer model. 4. Investigate the feasibility of detecting high-grade dysplasia and intramucosal carcinoma with the scanning probe using fresh human esophagectomy specimens with or without molecular contrast agents. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to develop and validate a new generation of scanning fiber-optic endoscopes and molecular contrast agents for improving early detection of cancer in luminal organs. The endoscope will be based on advanced micro-electro-mechanical systems (MEMS) technologies, overcoming limitations in current scanning endoscopes by offering fast 2-dimensional raster beam scanning and dynamic focus tracking while maintaining a small diameter (d3 mm). The proposed endoscope will enable real-time 3-D imaging and functional integration of high-resolution optical imaging techniques including optical coherence tomography (OCT) and confocal fluorescence endomicroscopy. The molecular contrast agents will be based upon fluorescently-labeled nanoparticles that display peptide ligands targeting dysplasia and early cancer cells. The excellent spatial resolution (< 5 5m) and 3-dimensional imaging capability offered by the scanning endoscope and the cancer-targeted nanoparticles providing enhanced contrast will significantly improve our currently limited ability for detecting early and pre-cancers. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1 Continuation Format Page