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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（由申请人提供）：小动物全身光学分子成像广泛用于研究体内基本生物学过程和加速药物开发。然而，实际的技术实现方式不允许发光标记物的3D生物分布的鲁棒定量呈现，并且需要与多路复用研究不兼容的冗长的采集时间。我们的假设是，通过采用结构光照明策略，并通过使用基于蒙特卡罗方法的重建算法，逆光学分子成像问题可以准确地解决，以提供定量的空间分布的分子荧光标记物在小动物的内部器官，同时为多个标记物的地图。该提案的目的是开发、表征和验证一种新型临床前成像平台，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，将能够提供定量荧光断层扫描数据在体内多路复用的研究。第二，我们提出开发新的重建算法来进行多光谱时间分辨光学重建。该算法将基于蒙特卡罗方法，用于复杂几何形状中的精确光传播模型和复杂照明策略。第三，我们将表征这种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。我们将基于高功率近红外激光器、数字微镜器件（DMD）和时间分辨分光光度计的非接触式光学成像仪集成在一起。重建算法的基础上的伴随蒙特卡罗制定将同时开发模型在小动物的光传播，并执行荧光产量和寿命重建。在体外验证成像平台后，将进行NIR-配体标记的FRET对的全身体内小动物成像。这一新系统将填补临床前研究中一个重要的未满足需求。该研究提案有望彻底改变体内基本生物过程的研究，并通过为整个动物的分子成像研究提供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。