Bridging the scales: Modeling macroscopic imaging from microscopy

NSERC的这项建议旨在开发新的技术来测量复杂和现实环境中的氧气输送并对其进行建模。我们将开发联合的3光子和光学相干断层扫描(OCT)显微成像，以在体内评估血管拓扑和红细胞动力学如何改变神经组织的氧合。利用脑组织中微血管拓扑、血流和氧气的测量，我们将建立和验证基于平流/扩散方程的描述组织氧气输送的第一性原理物理学模型。这些模型将用来模拟用磁共振成像测量的宏观信号的物理学。作为第二个研究方向，我们的目标是开发工具来研究氧输送受损的结构相关性。将设计一种定制的成像系统，以获得体外3D的大型组织切片数据集。将开发图像处理工具，将全脑显微3D渲染与活体MRI图像进行联合配准，并分割血管和白质描述符。他们将被用来用显微镜来验证和模拟新的MRI白质测量，目的是提炼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核磁共振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，使这座桥梁能够跨越尺度。

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.