Reference number : GC-2017-Q1-01572, amendment number : , agreement type : G, recipient legal name : Pike, Gilbert (University of Calgary), recipient country : CA, recipient province : nan, recipient city : Alberta, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : 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., program purpose french : 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., agreement title english : MRI of White Matter Microstructure, agreement title french : MRI of White Matter Microstructure, agreement number : RGPIN, agreement value : 435000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada