Abstract

PurposeTo investigate the effect of realistic microstructural geometry on the susceptibility‐weighted MR signal in white matter (WM), with application to demyelination.MethodsPrevious work has modeled susceptibility‐weighted signals under the assumption that axons are cylindrical. In this study, we explored the implications of this assumption by considering the effect of more realistic geometries. A three‐compartment WM model incorporating relevant properties based on the literature was used to predict the MR signal. Myelinated axons were modeled with several cross‐sectional geometries of increasing realism: nested circles, warped/elliptical circles, and measured axonal geometries from electron micrographs. Signal simulations from the different microstructural geometries were compared with measured signals from a cuprizone mouse model with varying degrees of demyelination.ResultsSimulation results suggest that axonal geometry affects the MR signal. Predictions with realistic models were significantly different compared with circular models under the same microstructural tissue properties, for simulations with and without diffusion.ConclusionThe geometry of axons affects the MR signal significantly. Literature estimates of myelin susceptibility, which are based on fitting biophysical models to the MR signal, are likely to be biased by the assumed geometry, as will any derived microstructural properties. Magn Reson Med 79:489–500, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Highlights

  • Myelin microstructure in white matter (WM) is important for healthy brain function and in neurological disease

  • Following empirical works demonstrating that the frequency dependent magnetic resonance (MR) signal may reflect localized differences in magnetic susceptibility χ [7,8,9], recent studies have shown that the magnetic susceptibility of myelin strongly influences the gradient echo (GRE) signal, including both signal phase and magnitude [10,11,12,13,14]

  • We first investigate the effect of geometry of a single axon on the local magnetic field perturbation

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Summary

Introduction

Myelin microstructure in white matter (WM) is important for healthy brain function and in neurological disease. In human and animal brains, normal myelin formation supports healthy development and promotes vital processes such as neuroplasticity [1]. Given myelin’s important role in brain function, a longstanding goal in human neuroscience has been to noninvasively estimate properties of myelin – its volume fraction in WM, or intact myelin volume fraction – from the MR signal. Myelin has a magnetic susceptibility χ that is offset to its environment. This arises from myelin’s unique chemical composition and ordering of phospholipids within the myelin sheath structure. Following empirical works demonstrating that the frequency dependent MR signal (e.g. spectroscopic imaging) may reflect localized differences in magnetic susceptibility χ [7,8,9], recent studies have shown that the magnetic susceptibility of myelin strongly influences the gradient echo (GRE) signal, including both signal phase and magnitude [10,11,12,13,14]

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