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

• 批准号: 8410480
• 负责人: Katsuo Kurabayashi
• 金额: $ 45.01万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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/8410480
• 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

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.

描述（由申请人提供）：体内分子表达的靶向多光谱双轴共聚焦成像，该BRP的长期长期目标是开发一种微型的内部成像仪器，以研究活动物上皮细胞中癌症生物学的分子机制。这种新型的光学设计使用离轴照明和光收集来产生较高的动态范围，用于收集垂直的横截面荧光图像。我们将组建一个来自密歇根大学工程学院和医学院的调查人员跨学科的研究小组。具体目的是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细胞中结合异常增生的亲和力肽，在乳腺血管内皮中和3）中的CXCR7和3）以在现场动物模型中验证成像性能。双轴共聚焦体系结构使用两个单独的低数值孔径目标的重叠焦点，以实现亚细胞分辨率和较长的工作距离。瞄准后扫描提供了巨大的视野以及光学的可伸缩性和微型化，并且复制的抛物线镜将准直的，多光谱的光束引导到共同的焦点。这种独特的设计可以在基础方向上查看上皮分化模式。上皮的实时成像将通过开发垂直执行器来实现，该垂直执行器使用具有大小，速度，力和线性的薄膜压电材料来克服运动伪影（> 10帧/秒）。该设备将与由参数共振驱动的横向扫描微型摩尔相结合。使用噬菌体显示的技术，将选择亲和力的肽，该技术通过对高度表达与肿瘤相关的表达表面靶标的细胞和组织进行生物群体。可以将多个探针标记为近红外，以达到预期的组织穿透深度（> 500微米）。成像性能将通过将微型原型插入结肠来验证，以评估远端粘膜上皮或放在胸部上以对活动物的乳腺癌上皮形象成像。公共卫生：这种通用仪器可用于研究具有亚细胞分辨率，高动态范围和完整成像深度的活动物模型上皮中的分子过程，从而允许对癌症生物学机制的纵向研究，并为药物发现提供了新的平台。