Bridging the scales: Modeling macroscopic imaging from microscopy

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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.