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摘要该提案是一个协作、多团队和多学科的项目，涉及来自华盛顿大学生物工程、电气工程、机械工程、医学和病理学系的研究人员。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，以提高腔内器官癌症的早期检测。内窥镜将基于先进的微电子机械系统(MEMS)技术，通过提供快速的二维光栅束扫描和动态焦点跟踪，同时保持小直径(D3 Mm)，克服当前扫描内窥镜的局限性。通过这项计划，将开发两种优势互补的微扫描仪技术，每种技术都旨在实现内窥镜应用技术类别的最佳性能。为了在快速变化的环境中进行大面积成像，将开发一种大扫描角度的高速悬臂梁波导扫描器。将开发一种具有主动焦点跟踪功能的微镜扫描仪，用于高分辨率三维成像。这两项技术的展示为未来在单一内窥镜通道中整合这两种功能开辟了一条道路。提出的内窥镜将实现实时3-D成像和高分辨率光学成像技术的功能集成，包括光学相干层析成像(OCT)和共焦荧光内窥镜。分子造影剂将基于荧光标记的纳米颗粒，这些纳米颗粒显示针对异型增生和早期癌细胞的多肽配体。这项建议旨在通过克服以下挑战来推进当前的内窥镜技术：(1)实现均匀、可控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微弱内在对比；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米)和三维成像能力将显著改善我们目前有限的检测早期和癌前病变的能力。本项目的具体目标是：1.研制一种小型化的波导型悬臂梁扫描仪，能够以大视场(&gt；60：)的速度快速扫描波束(&gt；20 kHz谐振频率)，用于大范围的实时成像。2.开发可变形的MEMS扫描微镜和光学封装，具有高分辨率(&lt；5.5米)和动态焦点跟踪(1 mm深度范围)，以实现高质量的三维成像。3.在仓鼠颊囊癌模型中评价扫描内窥镜对正常和早期癌的高分辨率OCT和共聚焦荧光成像的性能。4.应用分子造影剂或不加分子造影剂的新鲜人食道切除标本，探讨扫描探针检测高度不典型增生和粘膜内癌的可行性。公共卫生相关性：这项建议的目标是开发和验证新一代扫描光纤内窥镜和分子造影剂，以改进腔器官癌症的早期检测。内窥镜将基于先进的微电子机械系统(MEMS)技术，通过提供快速的二维光栅束扫描和动态焦点跟踪，同时保持小直径(D3 Mm)，克服当前扫描内窥镜的局限性。提出的内窥镜将实现实时3-D成像和高分辨率光学成像技术的功能集成，包括光学相干层析成像(OCT)和共焦荧光内窥镜。分子造影剂将基于荧光标记的纳米颗粒，这些纳米颗粒显示针对异型增生和早期癌细胞的多肽配体。扫描内窥镜提供的卓越空间分辨率(5.5米)和三维成像能力，以及针对癌症的纳米颗粒提供的增强对比度，将显著改善我们目前有限的检测早期和癌症前期的能力。PHS 398/2590(09/04版，2006年4月4日重新发布)第1页续订格式页

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