Technology development for in vivo deep tissue imaging

体内深层组织成像技术开发

• 批准号: 8604711
• 负责人: CHRIS XU
• 金额: $ 33.33万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604711
• 关键词: Biological; Biomedical Research; Brain; Characteristics; Collaborations; Databases; Development; Feedback; Fiber; Fluorescence Microscopy; Fluorescent Dyes; Frequencies; Generations; Goals; Image; Imaging Device; Knowledge; Lasers; Measures; Methodology; Microscope; Microscopic; Microscopy; Modality; Mus; Neurons; Optics; Output; Penetration; Photons; Physiologic pulse; Proteins; Rattus; Research; Research Personnel; Resolution; Science; Signal Transduction; Source; Supervision; System; Testing; Time; Tissues; Vendor; Width; Work; base; biological research; design; fluorophore; improved; in vivo; innovation; lens; new technology; novel; photonics; programs; retinal rods; technology development

DESCRIPTION (provided by applicant): The goal of this research program is to explore new laser technologies, new spectral windows, and three- photon fluorescence microscopy for imaging deep into scattering tissues, and then demonstrate the new methodologies in in vivo biological imaging. The proposed research consists of two sequential thrusts: the first involves the development of a novel energetic excitation source for the exploration of the new spectral window between 1600 and 1800 nm (i.e., the 1700-nm spectral window) with significantly reduced tissue scattering; the second thrust concentrates on demonstrating the new methodologies for in vivo deep tissue imaging based on three-photon excitation, improving the signal-to-background ratio by orders of magnitude and extending the depth penetration of multiphoton imaging. The proposed program is based on three major innovations: (1) 1700-nm spectral window for significantly reduced tissue scattering, (2) 3PE as a new excitation modality to simultaneously improve the SBR and extend the accessibility of fluorophores in deep tissue imaging, and (3) an excitation source tailored for in vivo deep tissue three-photon fluorescence microscopy at the 1700-nm spectral window by using soliton self-frequency shift in a photonic crystal rod to generate energetic, wavelength tunable solitons seeded from a fiber laser. We aim to demonstrate a new generation of multiphoton microscopic imaging tool that can reach an ultimate imaging depth of 3 mm or beyond within intact biological tissues such as the mouse or rat brain. The successful completion of this program will have a broad impact on a wide variety of biological and biomedical research fields where high-resolution imaging deep within intact tissue is required.

描述(申请人提供)：该研究项目的目标是探索新的激光技术、新的光谱窗口和三光子荧光显微镜，以深入到散射组织进行成像，然后展示体内生物成像的新方法。这项研究包括两个顺序的推进：第一个是开发一种新的高能激发源，用于探索1600到1800 nm之间的新光谱窗口(即1700 nm光谱窗口)，显著降低组织散射；第二个推进是展示基于三光子激发的活体深部组织成像的新方法，将信本底比提高一个数量级，并扩大多光子成像的深度穿透。提出的计划基于三项重大创新：(1)用于显著减少组织散射的1700 nm光谱窗口，(2)3PE作为一种新的激发方式，以同时改善SBR，并扩大深部组织成像中荧光团的可及性，以及(3)通过利用光子晶体棒中的孤子自频移来产生从光纤激光器种子产生的高能、波长可调的孤子，从而在1700 nm光谱窗口为活体组织三光子荧光显微镜量身定做激发源。我们的目标是展示新一代多光子显微成像工具，该工具可以在完整的生物组织(如小鼠或大鼠大脑)内达到3毫米或更深的最终成像深度。该计划的成功完成将对各种生物和生物医学研究领域产生广泛的影响，这些领域需要在完整组织的深处进行高分辨率成像。