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建平台， 辐射传输方程（RTE）的解决方案，将开发用于准确和稳健的体内成像， 小动物体内的荧光靶点。虽然小动物光学层析成像系统最近已经被 引入，目前的系统不采用荧光或生物发光，这已被限制为 平面投影此外，当前的光学断层扫描系统依赖于使用时间无关的 测量和重建算法的基础上的扩散近似。但众所周知 小鼠的小体积和异质性呈现出扩散近似不适用的条件， 有效的.认识到这一点，基于传输的解决方案的RTE已被研究作为一个有前途的替代方案。 然而，迄今为止的方法依赖于数值方法，其不具有准确性或效率 需要商业部署。在第一阶段的研究中，Transpire解决RTE的算法是 成功应用于概念验证过程，利用了IBM在频域方面的专业知识 光子迁移（FPDM），用于重建3-D小鼠模型中的荧光团浓度。二期 研究将扩展这项工作，以开发基于RTE的断层重建软件平台， FDPM光子迁移。具体目标是：（1）开发一个优化的三维RTE求解器 激发光和发射光在前向和伴随模式下的传播，用于小动物成像的流线型 条件下的非接触，非匹配介质;（2）开发一种自适应非线性算法， 用于小动物体积中荧光产量重建的正向和伴随RTE解决方案;（3）使 通过开发从microCT图像自动生成网格的混合microCT/光学成像;（4）集成 将上述组件整合到FDPM断层重建的自动化软件系统中;以及（5） 通过肽靶向近红外成像和可见荧光定量证明商业可行性 异种移植小鼠中的造影剂。第二阶段的成功完成将产生一个自动化的软件 产品，当结合思科在频域荧光硬件技术方面的专业知识时 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.