Multispectral Fluorescence Molecular Tomography with Structured Light

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过程和加速药物开发。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渲染，并且需要较长的采集时间，与多路复用研究不兼容。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，可以精确地解决光学分子逆成像问题，提供分子荧光标记物在小动物内脏中分布的定量空间图，同时提供多个标记物的定量空间图。本提案的目标是开发，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复用研究提供定量荧光层析数据。其次，我们提出了一种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，用于复杂几何形状和复杂照明策略的精确光传播模型。第三，我们将描述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。我们将集成基于高功率近红外激光器的非接触式光学成像仪，数字微镜器件（DMD）和时间分辨分光光度计。将同时开发基于伴随蒙特卡罗公式的重建算法，以模拟光在小动物中的传播，并执行荧光产量和寿命重建。在体外验证成像平台后，将对nir配体标记的FRET对进行体内小动物全身成像。这个新系统将填补临床前研究中一个重要的未满足的需求。该研究计划有望通过为全动物分子成像研究提供一种高灵敏度和高通量的新成像工具，从而彻底改变体内基本生物过程的研究，并大大加快药物开发。

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.