RTE/FDPM for optical imaging of cancer in small animal

RTE/FDPM 用于小动物癌症光学成像

• 批准号: 6934775
• 负责人: TODD A WAREING
• 金额: $ 12.56万
• 依托单位: TRANSPIRE, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934775
• 关键词: animal data; bioimaging /biomedical imaging; computer program /software; computer simulation; computer system design /evaluation; fluorescence; fluorescent dye /probe; image processing; ionophores; laboratory mouse; mathematical model; molecular /cellular imaging; neoplasm /cancer radiodiagnosis; optics; phantom model; radiation; three dimensional imaging /topography; tomography

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.

描述（由申请人提供）：在这个第一阶段申请中，我们寻求建立一种先进的确定性方法的可行性，用于解决商业上可行的小动物光学成像系统中使用的辐射传输方程（RTE）。迄今为止，使用荧光和生物发光的小动物光学成像仅限于非层析平面成像。然而，内部的异质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成像的有效性。虽然已经有人尝试使用扩散近似来预测小动物层析成像的光传播，但小鼠体内存在的小体积和异质性提供了扩散理论无效的条件。意识到这一点，基于运输的RTE解决方案已被确定为一个有前途的替代方案。然而，迄今为止的方法都依赖于数值方法，这些方法不具备有效重建小动物图像所需的准确性和效率。在拟议的研究中，Radion Technologies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层析成像重建。通过结合三阶精确空间差分、鲁棒加速方法和任意四面体单元的使用，所提出的方法非常适合准确有效地模拟输运和扩散状态。这项技术将被应用于利用频域光子迁移（FDPM）测量的荧光生成建模，该测量由德克萨斯农工大学的光子迁移实验室首创。本应用程序的具体目的是：(1)定量评估所提出的方法在激发和发射（荧光）波长处FDPM测量的前向预测的性能；(2)将这种方法用于图像重建，包括扩展现有的伴随解方法和开发过程控制驱动程序；(3)利用(a)加权反投影和(b)逆优化算法，从FDPM测量中重建荧光团吸收截面映射；(4)通过小鼠幻影横切面内荧光团浓度图像重建验证该方法。成功与否将根据所提出的方法准确重建荧光团浓度的能力来衡量，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将这一过程推向商业化，并展示基于rte的成像(i)肽靶向荧光造影剂在转移性癌症的异种移植小鼠中，以及（ii）转基因小鼠中GFR表达。