Bridging the scales: Modeling macroscopic imaging from microscopy

该NSERC提案旨在开发新技术，以测量和模拟复杂和现实环境中的氧气输送。我们将开发组合的3光子和光学相干断层扫描（OCT）显微成像，以评估在体内，血管拓扑结构和红细胞动力学如何改变神经组织的氧合。使用脑组织中的微血管拓扑结构，血流和氧气的测量，我们将建立和验证基于第一原理物理学的机械模型，描述基于平流/扩散方程的组织氧气输送。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。作为调查的第二流，我们的目标是开发工具，调查受损的氧气输送的结构相关性。定制成像系统将被设计为在3D中获得离体大组织切片数据集。将开发图像处理工具，以将全脑显微镜3D渲染与体内MRI图像配准，并分割血管和白质描述符。他们将被用来验证和模拟新的MRI白质措施与显微镜，目的是完善MRI作为成像工具的潜力。大型显微镜可以在成像细胞组成和MRI之间架起空间尺度的桥梁，我们的计划将导致一个现实的建模框架，以实现跨尺度的桥梁。

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.