RTE/FDPM for optical imaging of cancer in small animal models

项目摘要 在拟议的第二阶段研究中，一个商业上可行的软件重构平台，采用了 辐射输运方程(RTE)的解，将被开发用于精确和稳健的体内成像 小动物身上的荧光靶标。尽管小动物光学层析成像系统最近已经 介绍，目前的系统不使用荧光或生物发光，这已被限制在 平面投影。此外，目前的光学层析成像系统依赖于使用与时间无关的 基于扩散近似的测量和重建算法。然而，众所周知， 小鼠体内的小体积和异质性存在扩散近似不存在的情况 有效。意识到这一点，基于交通的RTE解决方案被研究为一种有前途的替代方案。 然而，到目前为止，这些方法都依赖于数值方法，这些方法没有精度或效率 商业部署所需。在第一阶段的研究中，Traspire求解RTE的算法是 成功应用于概念验证过程，利用BCM在频域的专业知识 光子迁移(FPDM)，用于重建3-D小鼠模型中的荧光团浓度。第二阶段 研究将扩展这项工作，以开发基于RTE的层析重建软件平台 FDPM光子迁移。具体目标是：(1)开发一个用于建模的优化三维RTE求解器 用于小动物成像的激励和发射光在前向和伴随模式中的传播 具有非接触、非匹配介质的条件；(2)开发一种自适应非线性算法，采用 用于在小动物体积中重建荧光产额的正演和伴随RTE解决方案；(3)实现 通过开发从MicroCT图像自动生成网格来实现MicroCT/光学成像的混合；(4)集成 将上述组件输入用于FDPM断层扫描重建的自动化软件系统；及(5) 通过对靶向近红外和可见荧光的多肽进行成像来定量展示商业可行性 异种移植小鼠的造影剂。成功完成第二阶段将产生一个自动化软件 产品与BCM在频域荧光硬件技术方面的专业知识相结合 小动物成像，可以产生商业上可行的小动物成像系统。

Project Summary In the proposed Phase II research, a commercially viable software reconstruction platform, employing the solution of the radiative transport equation (RTE), will be developed for accurate and robust in vivo imaging of fluorescent targets in small animals. Although small animal optical tomography systems have recently been introduced, current systems do not employ fluorescence or bioluminescence, which have been confined to planar projections. In addition, current optical tomography systems rely on the use of time independent measurements and reconstruction algorithms based on the diffusion approximation. However, it is well known that the small volumes and heterogeneities in mice present conditions where the diffusion approximation is not valid. Realizing this, transport based solutions of the RTE have been researched as a promising alternative. However, approaches to date have relied on numerical methods which do not have the accuracy or efficiency required for commercial deployment. In the Phase I research, Transpire's algorithms for solving the RTE were successfully applied towards a proof-of-concept process, employing BCM's expertise in frequency-domain photon migration (FPDM), for reconstruction of fluorophore concentrations in a 3-D mouse phantom. Phase II research will extend this work to develop an RTE based, tomographic reconstruction software platform for FDPM photon migration. The specific aims are: (1) to develop an optimized 3-D RTE solver for modeling excitation and emission light propagation in forward and adjoint modes, streamlined for small animal imaging conditions with non-contact, non-matching mediums; (2) to develop an adaptive non-linear algorithm employing forward and adjoint RTE solutions for fluorescence yield reconstructions in small animal volumes; (3) to enable hybrid microCT/optical imaging by developing automatic grid generation from microCT images; (4) to integrate the above components into an automated software system for FDPM tomographic reconstruction; and (5) to quantitative demonstrate commercial viability through imaging of a peptide targeted NIR and visible fluorescent contrast agent in xenograft mice. Successful completion of Phase II will result in an automated software product, when combined with BCM's expertise in hardware technologies for frequency-domain fluorescence small animal imaging, can result in a commercially viable small animal imaging system.