Mouse Modeling Techniques for Bioluminescence Tomography

描述(申请人提供)：生物发光断层扫描(BLT)和荧光分子断层扫描(FMT)是研究小动物分子和细胞活动的两种新方法。这些成像工具有助于诊断疾病、监测治疗并促进药物设计。小鼠的几何和光学建模是BLT/FMT的重要前提。该项目的目标是开发具有独特功能的新的老鼠建模技术，包括将老鼠的解剖分解为不同的“器官区域”的方案，用于基于知识的分割的可变形的小鼠图谱，用于确定器官区域的光学参数以最佳匹配透光成像实验的测量数据的分段恒定拟合程序，以及固有的补偿扩散近似、几何误差和其他因素引入的误差的能力。这些优点有助于提高BLT鼠标建模的准确性、效率和稳健性。我们的主要假设是，相对于目前从文献中获取光学参数的方法，所提出的建模技术将显著提高BLT重建的质量。其具体目标是：(1)建立一个活体小鼠透照成像实验的原型系统；(2)构建与真实小鼠在光子传播方面尽可能接近的小鼠数值模型，并开发一个用户友好的BLT应用软件包；(3)在数值模拟和体模实验中对所提出的建模技术进行评估和验证，并在小鼠研究中展示它们的优点。在该方法中，简化的鼠标几何模型和扩散近似模型相结合，从测量的透照成像数据中估计具有代表性的光学参数。小鼠模型将用于BLT图像重建。在这个项目完成后，所提出的老鼠建模技术将得到验证，并且BLT图像重建中的相关收益将被量化为源质心和总能量。

DESCRIPTION (provided by applicant): Bioluminescence tomography (BLT) and fluorescence molecular tomography (FMT) are two new modalities to study molecular and cellular activities in small animals. These imaging tools help diagnose diseases, monitor therapies and facilitate drug designs. Geometrical and optical modeling of mice is a critically important prerequisite for BLT/FMT. The goal of this project is to develop novel mouse modeling techniques with unique features including a scheme that decomposes the mouse anatomy into different "organ regions", a deformable mouse atlas for knowledge-based segmentation, a piecewise constant fitting procedure for determination of optical parameters of organ regions to optimally match measured data from transillumination imaging experiments, and an inherent capability of compensating for the errors introduced by the diffusion approximation, geometrical errors and other factors. All these advantages contribute to improve the accuracy, efficiency and robustness of the mouse modeling for BLT. Our primary hypothesis is that the BLT reconstruction quality will be significantly improved using the proposed modeling techniques relative to the current method in which optical parameters are taken from the literature. The specific aims are to (1) build a prototype system for transillumination imaging experiments of a living mouse; (2) construct the mouse numerical models, which are equivalent to the real mice as closely as possible in terms of photon propagation, and develop a user-friendly software package for BLT applications; and (3) evaluate and validate the proposed modeling techniques in numerical simulation and phantom experiments, and demonstrate their merits in mouse studies. In this approach, the simplified mouse geometrical models and diffusion approximation models are combined to estimate representative optical parameters from measured transillumination imaging data. The mouse models will be used for BLT image reconstruction. Upon the completion of this project, the proposed mouse modeling techniques will have been validated, and the associated gains in BLT image reconstruction will have been quantified in terms of source centroid and total energy.