Multi-Photon endomicroscope for real-time in vivo vertical sectioning

用于实时体内垂直切片的多光子内窥镜

• 批准号: 9261386
• 负责人: Kenn R Oldham
• 金额: $ 33.35万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-18 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9261386
• 关键词: Affinity; Alpha Cell; Animal Cancer Model; Antibodies; Architecture; Benchmarking; Binding; Biological; Biological Process; Biomedical Engineering; Caliber; Cancer Biology; Cancer Model; Cancerous; Cell Surface Proteins; Cell surface; Cells; Clinical; Colon; Colon Carcinoma; Colorectal Cancer; Communities; Coupled; Custom; Development; Device or Instrument Development; Diagnosis; Dimensions; Disease; Dissociation; Drug Kinetics; Dyes; Endoscopes; Engineering; Epithelial; Epithelium; Exhibits; Fiber; Film; Future; Gastrointestinal tract structure; Genetically Engineered Mouse; Goals; Human; Image; Imaging Device; In Vitro; Intellectual Property; Interdisciplinary Study; Kinetics; Label; Lateral; Licensing; Malignant Neoplasms; Measures; Medical; Medicine; Molecular Weight; Monitor; Morphologic artifacts; Motion; Mus; Noise; Optics; Penetration; Peptides; Performance; Reporter; Research Project Grants; Resected; Resolution; Scanning; Signal Transduction; Small Interfering RNA; Specimen; Speed; Standardization; Stroke; Technology; Thinness; Time; Tissue imaging; Tissues; Validation; Vascular Permeabilities; Work; animal imaging; base; claudin-1 protein; colon dysplasia; commercialization; density; design; flexibility; fluorophore; human disease; imaging study; imaging system; immunogenicity; improved; in vivo; in vivo imaging; instrument; knock-down; microendoscopy; mouse model; multi-photon; multidisciplinary; multiphoton imaging; novel; overexpression; public health relevance; targeted imaging; tissue phantom; tool; validation studies

 DESCRIPTION (provided by applicant): The goal of this Bioengineering Research Grant (BRG) is to produce a novel multi-photon microendoscopy instrument that can rapidly vary focal depth and thus produce real-time vertical cross-sectional images from biological tissue in vivo, and to validate instrument performance in imaging of targeted peptide markers for colon cancer. Relative to prior miniature multi-photon instruments, the proposed instrument will feature much faster axial scanning for cross-sectional imaging without motion artifacts (frame rate 5-10 Hz) while maintaining a small diameter (3.4 mm) for compatibility with small animal imaging in the gastrointestinal tract. Instrument performance is expected to meet goals of sub-cellular resolution and deep tissue penetration with substantial field of view. Instrument development will be based on a multi-disciplinary collaboration of medical and engineering expertise in actuation, instrument design, optics, and cancer biology. Axial (into-tissue) scanning capabilities will be provided by high-speed, large- stroke thin-film PZT vertical translational actuators. A fiber-coupled, remote scanning architecture will permit modular insertion of optimized optics and actuators in a small handheld instrument. Instrument verification will be performed through benchmarking against of resolution, penetration depth, frame rate, and signal-to-noise ratio on standardized targets and/or phantom tissues. Full instrument validation will be performed in studies of in vivo imaging of genetically-engineered mouse models of cancer. Mice will be labeled with both targeted, dye-labeled peptides and general tissue dyes. Peptides will be optimized for bonding to specific targets exhibited in human disease and the mouse model. The optimized peptide will be characterized for binding affinity. In vivo imaging of the peptide with different fluorescent reporters will be used to identify optimal operating parameters for deep multi-photon imaging and characterize instrument performance.