RTE/FDPM for optical imaging of cancer in small animal

描述(由申请人提供)：在这个第一阶段的申请中，我们寻求建立一种先进的确定性方法来求解辐射传输方程(RTE)的可行性，用于商业上可行的小动物光学成像系统。到目前为止，使用荧光和生物发光的小动物光学成像仅限于非断层平面成像。然而，内部不均一性和光的非几何传播大大降低了这些方法对组织内荧光或发光源的成像的有效性。虽然已经有人尝试使用扩散近似来预测用于断层扫描小动物成像的光传播，但老鼠体内存在的小体积和异质性提供了扩散理论不成立的条件。意识到这一点，基于交通的RTE解决方案已被认为是一种有前途的替代方案。然而，到目前为止，方法依赖于数值方法，这些方法不具备有效重建小动物图像所需的精度或效率。在拟议的研究中，Radion技术公司提供的已建立的商业辐射传输系统的能力和基础设施将用于小动物断层图像重建。通过结合三阶精度空间差分、稳健加速方法和使用任意四面体单元，所提出的方法非常适合于准确和高效地模拟输运和扩散区域。这项技术将被应用于使用频域光子迁移(FDPM)测量来模拟荧光产生，该测量是由德克萨斯A&M大学的光子迁移实验室首创的。本应用程序的具体目标是(1)定量评估所提议的在激发和发射(荧光)波长对FDPM测量进行正演预测的性能；(2)将该方法用于图像重建，包括扩展现有的伴随解方法和开发过程控制驱动程序；(3)使用(A)加权反投影和(B)逆优化算法重建FDPM测量的荧光团吸收截面图；以及(4)通过在小鼠模型的横截面内重建荧光团浓度图像来验证该方法。成功与否将取决于所提出的方法是否能够准确地重建荧光团浓度，同时具有适合最终商业实施的计算效率。如果成功，第二阶段将寻求进一步发展这一进程，走向商业化，并展示基于RTE的成像(I)多肽靶向荧光造影剂在患有转移性癌症的异种移植小鼠中的应用，以及(Ii)GFR在转基因小鼠中的表达。

DESCRIPTION (provided by applicant): In this Phase I application, we seek to establish the feasibility of an advanced deterministic approach for solving the radiative transport equation (RTE) for use within a commercially viable small animal optical imaging system. To date, small animal optical imaging using fluorescence and bioluminescence has been confined to non-tomographic planar imaging. However, internal heterogeneties and the non-geometrical propagation of light substantially reduce the effectiveness of these methods for imaging of intra-tissue sources of fluorescence or luminescence. While there have been attempts at predicting light propagation for tomographic small animal imaging using the diffusion approximation, the small volumes and heterogeneities present in mice provide conditions where diffusion theory is not valid. Realizing this, transport based solutions of the RTE have been idenfitied as a promising alternative. However, approaches to date have relied on numerical methods which do not possess the accuracy or efficiency required for effective small animal image reconstruction. In the proposed research, the capabilities and infrastructure of an established commercial radiation transport system provided by Radion Technologies will be leveraged for use in small animal tomographic image reconstruction. Through a combination of third order accurate spatial differencing, robust acceleration methods and the use of arbitrary tetrahedral elements, the proposed approach is well suited for accurately and efficiently modeling both transport and diffusive regimes. This technology will be applied towards modeling fluorescent light generation using frequency-domain photon migration (FDPM) measurements pioneered by the Photon Migration Laboratory at the Texas A&M University. The specific aims of this application are (1) to quantitatively evaluate performance of the proposed approach for forward predictions of FDPM measurements at the excitation and emission (fluorescent) wavelengths; (2) to adapt this approach for image reconstruction, including the extension of an existing adjoint solution method and development of a process control driver; (3) to reconstuct fluorophore absorption cross section mappings from FDPM measurements using (a) weighted back projection and (b) inverse optimization algorithms; and (4) to validate this approach through fluorophore concentration image reconstruction within cross sections of a mouse phantom. Success will be measured on the ability of the proposed approach to accurately reconstruct fluorophore concentrations while having a computational efficiency suitable for ultimate commercial implementation. If successful, Phase 2 will seek to further develop this process towards commercialization and to demonstrate RTE-based imaging of (i) peptide targeted fluorescent contrast agents in xenograft mice with metastatic cancer and (ii) GFR expression in transgenic mice.