High Resolution Multiplexed Fluorescence Tomography

高分辨率多重荧光断层扫描

基本信息

批准号：
8105072
负责人：
Mark Jonathan Niedre
金额：
$ 29.79万
依托单位：
NORTHEASTERN UNIVERSITY
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：
2010-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8105072
关键词：
Address Advanced Development Algorithms Animals Anodes Area Biological Biological Process Biomedical Research Complex Data Data Set Development Disease Disease Progression Early Diagnosis Elements Environment Fluorescence Fluorescent Probes Fluorochrome Glioma Goals Growth Human Image Imagery Imaging technology Label Lasers Life Light Molecular Molecular Probes Mus Nude Mice Optical Instrument Optics Performance Photons Physiologic pulse Proteins Resolution Scanning Scheme Simulate Slice Source Speed System Techniques Technology Testing Three-Dimensional Imaging Time Tissues Tube Work X-Ray Computed Tomography anti-cancer therapeutic data acquisition design fluorescence imaging fluorophore image reconstruction improved in vivo instrument instrumentation light scattering novel novel therapeutics photomultiplier pre-clinical public health relevance response tomography tool tumor tumor xenograft

项目摘要

DESCRIPTION (provided by applicant): Small animal fluorescence tomography has emerged as powerful biomedical research tool since it allows three-dimensional imaging of molecularly-targeted fluorescent probes and red-shifted fluorescent proteins in unperturbed environments in vivo. Despite significant advances in instrumentation and image reconstruction algorithms in recent years, fluorescence tomographic imaging technology remains far from optimized. Two critical limitations are the relatively poor image resolution (limited to 1 or 2 mm) due to the high degree of light scatter in biological tissues, and an inability to perform high-throughput imaging of many fluorescent targets simultaneously (i.e. "multiplexing"), largely due to the spectral overlap of common fluorophores, long data acquisition times and tissue autofluorescence. In this project, we will develop a highly novel fluorescence tomographic scanner that will address these critical limitations using a number of unique design elements including; i) high- speed time-gated photon counting detection of the earliest-transmitted and therefore least scattered photons through animals, thereby allowing imaging resolution approaching 250 5m without loss of sensitivity or accuracy, ii) fast acquisition of both hyperspectral and fluorescence lifetime data in about 1 minute per axial slice, allowing robust de-mixing of at least five concurrent fluorophores and rejection of tissue autofluorescence, iii) a high speed, pulsed supercontinuum light source for excitation of virtually any fluorophore in the red and near-infrared region. The system will image mice in sequential axial slices over 360 degrees in an instrument configuration analogous to X-ray Computed Tomography. We will demonstrate that the scanner is capable of high-resolution multiplexed imaging, first in complex fluorescent optical phantoms with simulated background autofluorescence, and secondly in nude mice with multiply-labeled human glioma (Gli-36 and GBM8) tumor xenografts. We anticipate that the system will have applications in many areas of biomedical research including studying disease development and response to novel therapeutics non- invasively in live animals. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a highly novel fluorescence tomographic imager for high- resolution multiplexed imaging of molecular probes and red-shifted fluorescent proteins in whole animals in vivo. The unique design of the scanner will allow rapid, concurrent acquisition of hyperspectral and temporal data sets in an optical instrument configuration analogous to X-ray Computed Tomography. Novel image reconstruction algorithms will allow robust de-mixing and visualization of at least five fluorescent constructs with a resolution close to 250 5m, offering unprecedented small animal imaging capabilities. We anticipate that the scanner will have many applications in biomedical research including studying disease development and response to novel therapeutics in vivo.

描述（由申请人提供）：小动物荧光断层扫描已成为强大的生物医学研究工具，因为它允许在体内不受干扰的环境中对分子靶向荧光探针和红移荧光蛋白进行三维成像。尽管近年来仪器和图像重建算法取得了显着进步，但荧光断层成像技术仍远未优化。两个关键限制是由于生物组织中的光散射程度较高而导致图像分辨率相对较差（仅限于 1 或 2 毫米），以及无法同时对许多荧光目标进行高通量成像（即“多路复用”），主要是由于常见荧光团的光谱重叠、数据采集时间长和组织自发荧光。在这个项目中，我们将开发一种高度新颖的荧光断层扫描仪，它将使用许多独特的设计元素来解决这些关键限制，包括： i) 高速时间选通光子计数检测最早传输的、因此通过动物散射最少的光子，从而使成像分辨率接近 250 5 m，而不会损失灵敏度或准确性，ii) 快速采集高光谱和荧光寿命数据每个轴向切片约 1 分钟，允许至少五个并发荧光团的稳健去混合并抑制组织自发荧光，iii) 高速脉冲超连续谱光源，用于激发几乎任何荧光团红色和近红外区域。该系统将在类似于 X 射线计算机断层扫描的仪器配置中对小鼠进行 360 度连续轴向切片成像。我们将证明该扫描仪能够进行高分辨率多重成像，首先是在具有模拟背景自发荧光的复杂荧光光学模型中，其次是在带有多重标记的人类神经胶质瘤（Gli-36 和 GBM8）肿瘤异种移植物的裸鼠中。我们预计该系统将在生物医学研究的许多领域得到应用，包括研究活体动物的疾病发展和对新疗法的非侵入性反应。公共健康相关性：该项目的目标是开发一种高度新颖的荧光断层成像仪，用于对整个动物体内的分子探针和红移荧光蛋白进行高分辨率多重成像。扫描仪的独特设计将允许在类似于 X 射线计算机断层扫描的光学仪器配置中快速、同时采集高光谱和时间数据集。新颖的图像重建算法将允许对至少五个分辨率接近 250 5m 的荧光结构进行稳健的去混合和可视化，从而提供前所未有的小动物成像能力。我们预计该扫描仪将在生物医学研究中有许多应用，包括研究疾病的发展和体内新疗法的反应。