Subventions et des contributions :
Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)
Introduction
Magnetic resonance imaging (MRI) is an exceptionally rich technology that can produce images of many different tissue properties. Examples in the brain include imaging neuronal activity, connectivity, and microstructure. This Discovery Grant focuses on microstructure. We will investigate four quantitative MR measures and determine how they can best work alone or in combination to characterize the microscopic fibers (axons and the insulating myelin wrapped around them) of white matter. Specifically, we aim to develop methods to measure white matter fiber density and myelin content independently, and combine them to quantitatively describe microstructure.
In recent work, we pioneered a novel MRI technique for i n vivo imaging of the myelin g-ratio, which is the ratio of the inner to outer diameter of a myelinated axon. While an individual axon has a diameter on the order of microns and typical in vivo imaging voxel are on the order of millimeters, we have shown that an aggregate g-ratio for all the axons in a voxel can be computed using a simple formula. The technique uses a multimodal MRI framework that combines a measurement sensitive to the axonal volume fraction (AVF) with one sensitive to the myelin volume fraction (MVF). However, robust measurement of the AVF and MVF remains a technical challenge.
Objectives
The overall objective of this project is to develop image acquisition and analysis methods to achieve precise, accurate, and time efficient imaging of white matter microstructure in vivo , with an emphasis on robust mapping of the relative (g-ratio) and absolute myelin thickness. This will be pursued via 5 aims:
Aim 1. Improve the accuracy of diffusion MRI-based axon volume fraction measurements.
Aim 2. Develop new fast myelin imaging techniques.
Aim 3. Design a single acquisition g-ratio imaging protocol.
Aim 4. Create a technique to measure the g-ratio for individual fiber tracts.
Aim 5. Devise a method to measure the absolute myelin thickness.
Approach
In Aim 1, we will revise existing diffusion models of white matter to improve the accuracy of AVF estimates. In Aim 2, we will exploit compressed sensing to accelerate existing MVF imaging and investigate alternate approaches to measure MVF. In Aim 3, we will develop simultaneous imaging of the AVF and MVF thereby producing a time efficient protocol without image alignment issues. In Aim 4, we will develop methods that will allow us to characterize different (e.g. crossing) fiber tracts within a voxel. Finally, in Aim 5 we will design a technique to estimate the absolute aggregate myelin thickness within a voxel.
Impact
The non-invasive characterization of tissue microstructure in vivo with MRI represents a major technical advance and has enormous potential for studying normal brain development as well as diagnosing, monitoring progression, and assessing treatment effects in white matter diseases such as multiple sclerosis.