权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Multispectral Fluorescence Molecular Tomography with Structured Light

结构光多光谱荧光分子断层扫描

基本信息

批准号：
8442236
负责人：
Xavier Intes
金额：
$ 14.33万
依托单位：
RENSSELAER POLYTECHNIC INSTITUTE
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：
2012-03-15 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8442236
关键词：
Algorithms Animal Model Animals Architecture Area Beds Biological Biological Process Biomedical Research Clinical Complex Computer software Data Data Set Development Devices Drug Formulations Environment Equipment Fluorescence Fluorescence Resonance Energy Transfer Fluorochrome Frequencies Funding Gene Expression Gene Proteins Goals Image Imaging Device Imaging Techniques Imaging problem Immunologics In Vitro Inflammatory Investigation Label Laser Scanning Confocal Microscopy Lasers Life Ligands Light Lighting Magnetic Resonance Imaging Malignant Neoplasms Mammography Maps Methods Microscopic Microscopy Modality Modeling Molecular Monte Carlo Method Neurodegenerative Disorders Nonionizing Radiation Optical Tomography Optics Organ Outcome Patients Pattern Penetration Performance Positron-Emission Tomography Process Property Proteins Research Research Proposals Resolution Sampling Signal Transduction Site Spectrophotometry Structure System Techniques Testing Time Tissues Translations Ultrasonography X-Ray Computed Tomography attenuation base clinical application cost digital drug development fluorophore imaging modality in vivo meetings molecular imaging multi-photon novel novel strategies optical imaging pre-clinical preclinical study protein function reconstruction single photon emission computed tomography time resolved data tomography tool

项目摘要

DESCRIPTION (provided by applicant): Whole-body optical molecular imaging of small animals is widely used to investigate fundamental biological processes in vivo and accelerate drug development. However, the actual technical implementations do not allow for robust quantitative rendering of 3D bio- distribution of the luminescent markers and require lengthy acquisition times incompatible with multiplexed studies. Our hypothesis is that by employing structured light illumination strategies and by using reconstruction algorithms based on the Monte Carlo method, the inverse optical molecular imaging problem can be solved accurately to provide quantitative spatial maps of molecular fluorescence markers distribution in the internal organs of small animals and simultaneously for multiply markers. The objective of this proposal is to develop, characterize and validate a novel pre-clinical imaging platform that will allow tracking in vivo multiple fluorophores in small animals. First, we intend to develop a fluorescence molecular small animal imager that will be able to provide quantitative fluorescent tomographic data for in vivo multiplexed study. Second, we propose to develop new reconstruction algorithm to perform multispectral time-resolved optical reconstructions. The algorithm will be based on the Monte Carlo method for accurate light propagation model in complex geometry and for complex illumination strategies. Third, we will characterize the performances of this new enabling platform to perform Fluorescence Resonance Energy Transfer (FRET) imaging in vivo. We will integrate a non-contact optical imager based on high-power NIR laser, Digital Micromirror Device (DMD) and time-resolved spectrophotometer. Reconstruction algorithms based on an adjoint Monte Carlo formulation will be developed concurrently to model light propagation in small animal and to perform fluorescent yield and lifetime reconstructions. After validating the imaging platform in vitro, whole-body in vivo small animal imaging of NIR-ligand labeled FRET pair will be performed. This new system will fill an important unmet need in pre-clinical studies. This research proposal is expected to revolutionize the investigation of fundamental biological processes in vivo and considerably accelerate drug development by providing a new imaging tool with high-sensitivity and high-throughput capability for molecular imaging studies in whole animals.

描述(申请人提供)：小动物的全身光学分子成像被广泛用于研究体内的基本生物学过程，并加速药物开发。然而，实际的技术实现不允许对发光标记的3D生物分布进行稳健的定量呈现，并且需要与多路复用研究不兼容的长采集时间。我们的假设是，通过采用结构光照明策略和基于蒙特卡罗方法的重建算法，可以准确地解决光学分子成像逆问题，从而提供小动物内部分子荧光标记分布的定量空间图，同时为多个标记提供定量的空间分布图。这项建议的目标是开发、表征和验证一种新的临床前成像平台，该平台将允许在小动物体内跟踪多个荧光团。首先，我们打算开发一种荧光分子小动物成像仪，它将能够为体内多路研究提供定量的荧光断层扫描数据。其次，我们建议开发新的重建算法来执行多光谱时间分辨光学重建。该算法将基于蒙特卡罗方法，以求在复杂几何形状和复杂照明策略中建立准确的光传播模型。第三，我们将表征这一新的使能平台在体内进行荧光共振能量转移(FRET)成像的性能。我们将集成基于高功率近红外激光器、数字微镜(DMD)和时间分辨分光光度计的非接触式光学成像仪。基于伴随蒙特卡罗公式的重建算法将同时开发，以模拟小动物的光传播，并执行荧光产量和寿命重建。在体外验证了成像平台后，将对NIR-配体标记的FRET对进行体内整体小动物成像。这一新系统将填补临床前研究中未得到满足的一个重要需求。这一研究方案有望为体内基本生物学过程的研究带来革命性的变化，并通过为整个动物的分子成像研究提供一种具有高灵敏度和高通量能力的新成像工具，大大加快药物开发。