Targeted Multi-Spectral Dual Axes Confocal Imaging of In Vivo Molecular Expressio

体内分子表达的靶向多光谱双轴共焦成像

基本信息

批准号：
8206731
负责人：
Katsuo Kurabayashi
金额：
$ 48.77万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-25 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8206731
关键词：
Affinity Animal Model Animals Architecture Behavior Binding Biological Phenomena Biomedical Engineering Breast Breast Cancer Cell Cancer Biology Cell Communication Cell surface Cells Chest Collection Colon Colon Carcinoma Colon Hyperplastic Polyp Colorectal Cancer Detection Development Devices Dimensions Distal Diversity Library Duct (organ) structure Dyes Dysplasia Electronics Engineering Epithelial Epithelium Film Fluorescence Genetically Engineered Mouse Goals Hyperplasia Image Implant Investigation Label Lateral Lead Life Ligands Light Lighting Longitudinal Studies Malignant Neoplasms Michigan Microscope Miniaturization Molecular Morphologic artifacts Motion Mucous Membrane Mus Neoplasms Normal tissue morphology Optics Pattern Penetration Peptides Performance Phage Display Process Public Health Research Research Personnel Resolution Scanning Source Speed Surface Techniques Thick Time Tissues Translating Tumor Angiogenesis Universities Vascular Endothelium Work Xenograft Model Xenograft procedure cancer imaging chemokine receptor college design detector drug discovery flexibility fluorescence imaging fluorescence microscope in vivo innovation instrument malignant breast neoplasm medical schools mouse model novel optical imaging prototype public health relevance receptor

项目摘要

DESCRIPTION (provided by applicant): Targeted Multi-Spectral Dual Axes Confocal Imaging of In Vivo Molecular Expression The broad, long-term objective of this BRP is to develop a miniature intra-vital imaging instrument to study molecular mechanisms of cancer biology in the epithelium of live animals. This novel optical design uses off-axis illumination and collection of light to produce superior dynamic range for collecting vertical cross-sectional fluorescence images. We will assemble an inter-disciplinary team of investigators from the College of Engineering and the School of Medicine at the University of Michigan. The specific aims are 1) to develop a scanning mechanism to achieve real time, multi- spectral vertical cross-sectional imaging, 2) to select affinity peptides that bind to dysplasia in colonic mucosal epithelium and to CXCR7 in breast vascular endothelium, and 3) to validate imaging performance in live animal models. The dual axes confocal architecture uses the overlapping focus of two separate low numerical aperture objectives to achieve sub-cellular resolution and long working distance. Post-objective scanning provides a large field-of-view as well as scalability and miniaturization of the optics, and a replicated parabolic mirror directs collimated, multi-spectral beams to a common focus. This unique design can view the epithelial differentiation pattern in the basilar to luminal direction. Real time imaging of the epithelium will be achieved by developing a vertical actuator that uses thin film piezoelectric materials that have the size, speed, force, and linearity to overcome motion artifact (>10 frames/sec). This device will be combined with a lateral scanning micro-mirror that is driven by parametric resonance. Affinity peptides will be selected using the technique of phage display by biopanning a high diversity library against cells and tissues that over express surface targets associated with neoplasia. Multiple probes can be near-infrared labeled to achieve the tissue penetration depths expected (>500 microns). Imaging performance will be validated by inserting the miniature prototype into the colon to evaluate the epithelium of the distal mucosa or by placing against the chest to image the epithelium of breast ducts of live animals. Public Health: This general purpose instrument can be used to study molecular processes in the epithelium of live animal models with sub-cellular resolution, high dynamic range, and full imaging depth, allowing for longitudinal investigation of mechanisms of cancer biology and providing a new platform for drug discovery. PUBLIC HEALTH RELEVANCE: Project Narrative Completion of these aims will deliver a general purpose instrument for imaging the epithelium in live animals with superior depth and dynamic range, allowing for study of molecular mechanisms of cancer and providing a new platform for drug discovery.

描述（由申请人提供）：体内分子表达的靶向多光谱双轴共焦成像该 BRP 的广泛、长期目标是开发一种微型活体成像仪器，以研究上皮细胞中癌症生物学的分子机制活体动物。这种新颖的光学设计使用离轴照明和光收集来产生卓越的动态范围，用于收集垂直截面荧光图像。我们将组建一个由来自密歇根大学工程学院和医学院的跨学科研究人员组成的团队。具体目标是 1) 开发一种扫描机制以实现实时、多光谱垂直横截面成像，2) 选择与结肠粘膜上皮异常增生和乳腺血管内皮中 CXCR7 结合的亲和肽，以及 3)验证活体动物模型的成像性能。双轴共焦架构利用两个独立的低数值孔径物镜的重叠焦点来实现亚细胞分辨率和长工作距离。后物镜扫描提供了大视场以及光学器件的可扩展性和小型化，并且复制的抛物面镜将准直的多光谱光束引导到公共焦点。这种独特的设计可以观察基底到管腔方向的上皮分化模式。上皮的实时成像将通过开发一种垂直致动器来实现，该致动器使用薄膜压电材料，其尺寸、速度、力和线性度可以克服运动伪影（> 10 帧/秒）。该设备将与由参数共振驱动的横向扫描微镜相结合。将使用噬菌体展示技术，通过对过度表达与肿瘤相关的表面靶标的细胞和组织进行生物淘选高多样性文库来选择亲和肽。可以对多个探针进行近红外标记，以达到预期的组织穿透深度（> 500 微米）。通过将微型原型插入结肠以评估远端粘膜的上皮或通过放置在胸部以对活体动物的乳腺导管上皮进行成像来验证成像性能。公共卫生：这种通用仪器可用于研究活体动物模型上皮的分子过程，具有亚细胞分辨率、高动态范围和全成像深度，可对癌症生物学机制进行纵向研究并提供新平台用于药物发现。公共卫生相关性：项目叙述完成这些目标将提供一种通用仪器，用于对活体动物的上皮细胞进行成像，具有卓越的深度和动态范围，从而可以研究癌症的分子机制，并为药物发现提供新的平台。