Technology development for in vivo deep tissue imaging

体内深层组织成像技术开发

基本信息

批准号：
8442238
负责人：
CHRIS XU
金额：
$ 44.18万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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（由申请人提供）：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，以对散射组织深处进行成像，然后展示体内生物成像的新方法。拟议的研究由两个连续的主旨组成：第一个涉及开发一种新型高能激发源，用于探索1600至1800 nm之间的新光谱窗口（即1700 nm光谱窗口），并显着减少组织散射；第二个重点是展示基于三光子激发的体内深层组织成像新方法，将信号背景比提高几个数量级，并扩展多光子成像的深度穿透力。拟议的计划基于三项主要创新：(1) 1700 nm 光谱窗口可显着减少组织散射，(2) 3PE 作为新的激发方式，可同时改进 SBR 并扩展深部组织成像中荧光团的可及性，以及(3) 为 1700 nm 光谱窗口的体内深层组织三光子荧光显微镜量身定制的激发源，通过使用光子晶体棒中的孤子自频移来产生高能、波长可调的孤子从光纤激光器播种。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（例如小鼠或大鼠大脑）内达到 3 毫米或以上的最终成像深度。该计划的成功完成将对需要完整组织深处高分辨率成像的各种生物和生物医学研究领域产生广泛影响。