Bridging the scales: Modeling macroscopic imaging from microscopy

这项NSERC提案旨在开发在复杂和现实环境中测量和模拟氧气输送的新技术。我们将开发联合3光子和光学相干断层扫描（OCT）显微镜成像来评估体内血管拓扑结构和红细胞动力学如何改变神经组织氧合。通过测量微血管拓扑结构、血流和脑组织中的氧气，我们将建立并验证基于平流/扩散方程的第一性原理物理机制模型，该模型描述了氧气向组织的输送。这些模型将用于模拟磁共振成像测量的宏观信号的物理特性。作为研究的第二流，我们的目标是开发工具来研究受损氧输送的结构相关性。将设计一个定制的成像系统，以获得体外三维的大型组织切片数据集。将开发图像处理工具，将全脑微观3D渲染图与体内MRI图像共同注册，并分割血管和白质描述符。它们将用于验证和模拟新的MRI白质测量显微镜，目的是完善MRI作为成像工具的潜力。大规模显微镜可以在成像细胞组成和MRI之间的空间尺度上架起桥梁，我们的项目将导致一个现实的建模框架，使这种跨越尺度的桥梁成为可能。

This NSERC proposal aims to develop novel technology to measure and model oxygen delivery in complex and realistic environments. We will develop combined 3-photon and Optical Coherence Tomography (OCT) microscopy imaging to assess in vivo, how vascular topology and RBC dynamics change neural tissue oxygenation. Using measures of microvascular topology, blood flow and oxygen in brain tissue, we will build and validate first-principles physics-based mechanistic models describing oxygen delivery to tissue based on advection/diffusion equations. These models will serve to simulate the physics of macroscopic signals measured with Magnetic Resonance Imaging. As a secondary stream of investigation, we aim to develop tools to investigate structural correlates of impaired oxygen delivery. A custom imaging system will be designed to obtain large tissue section datasets ex vivo in 3D. Image processing tools to co-register whole brain microscopic 3D renderings to in vivo MRI images and to segment vascular and white-matter descriptors will be developed. They will be used to validate and model novel MRI white-matter measures with microscopy with the aim of refining the potential of MRI as an imaging tool. Large-scale microscopy can bridge spatial scales between imaging cellular composition and MRI and our program will lead to a realistic modeling framework to enable this bridge across scales.