A New Integrated Endoscope System

描述（由申请人提供）：新型集成内窥镜系统项目总结本提案是一项协作、多团队和多学科项目，涉及来自华盛顿大学生物工程、电气工程、机械工程、医学和病理学系的研究者。其目的是开发和验证新一代扫描光纤内窥镜和分子造影剂，以改善管腔器官中癌症的早期检测。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将通过该计划开发，每种技术都旨在实现内窥镜应用技术类别中的最佳性能。为了在快速变化的环境中进行大面积成像，研制了一种宽扫描角的高速悬臂梁波导扫描器。一种具有主动聚焦跟踪的微镜扫描器将被开发用于高分辨率的3D成像。这两种技术的演示为将来在单个内窥镜通道中集成这两种功能开辟了一条道路。拟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）和共焦荧光显微内镜。分子造影剂将基于荧光标记的纳米颗粒，其显示靶向异型增生和早期癌细胞的肽配体。该提案旨在通过克服以下挑战来推进当前的内窥镜技术：（1）用于实现均匀、可控的扫描图案和三维成像能力的内窥镜光束扫描技术;（2）在各种成像深度上保持高分辨率;（3）探头小型化;（4）正常组织与癌前或早期癌症之间的弱内在对比度;（5）在正常组织与癌前或早期癌症之间的弱内在对比度。以及（5）缺乏对早期癌症的分子特异性。目标空间分辨率（<5 5 m）和三维成像能力将显着提高我们目前有限的检测早期和癌前病变的能力。该项目的具体目标是：1。研制了一种小型化的波导悬臂梁扫描器，能够进行快速光束扫描（> 20 kHz谐振频率）和宽视场（>60：）的实时成像。2.开发可变形MEMS扫描微镜和光学封装，具有高分辨率（<5 5 m）和动态焦点跟踪（1 mm深度范围），可实现高质量的三维成像。3.评价扫描内窥镜在体内仓鼠颊囊癌模型中用于正常和早期癌症的高分辨率OCT和共焦荧光成像的性能。4.使用新鲜的人食管切除标本（含或不含分子造影剂），研究扫描探头检测高度异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，以提高管腔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。拟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）和共焦荧光显微内镜。分子造影剂将基于荧光标记的纳米颗粒，其显示靶向异型增生和早期癌细胞的肽配体。扫描内窥镜提供的出色的空间分辨率（< 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着改善我们目前检测早期和癌前病变的有限能力。PHS 398/2590（2004年9月修订，2006年4月重新印发）第1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