Abstract
White matter is composed of irregularly packed axons leading to a structural disorder in the extra-axonal space. Diffusion MRI experiments using oscillating gradient spin echo sequences have shown that the diffusivity transverse to axons in this extra-axonal space is dependent on the frequency of the employed sequence. In this study, we observe the same frequency-dependence using 3D simulations of the diffusion process in disordered media. We design a novel white matter numerical phantom generation algorithm which constructs biomimicking geometric configurations with few design parameters, and enables to control the level of disorder of the generated phantoms. The influence of various geometrical parameters present in white matter, such as global angular dispersion, tortuosity, presence of Ranvier nodes, beading, on the extra-cellular perpendicular diffusivity frequency dependence was investigated by simulating the diffusion process in numerical phantoms of increasing complexity and fitting the resulting simulated diffusion MR signal attenuation with an adequate analytical model designed for trapezoidal OGSE sequences. This work suggests that angular dispersion and especially beading have non-negligible effects on this extracellular diffusion metrics that may be measured using standard OGSE DW-MRI clinical protocols.
Highlights
Diffusion-weighted magnetic resonance imaging, sensitized to the diffusive motion of water along the direction of an applied magnetic field gradient, has become a well-established technique to non-invasively probe the cellular organization of tissues in vivo
Some Oscillating Gradient Spin Echo (OGSE) studies have reported that, at frequencies below 400 Hz, the OG-measured extra-axonal diffusivity transverse to axons in white matter is linearly dependent on the frequency of the employed OGSE sequence [2], whereas state-of-the art multi-compartment models of white matter relying on Pulsed Gradient Spin Echo (PGSE) or OGSE sequences usually assume a Gaussian diffusion in the extra-axonal space [3,4,5,6]
According to Budde and Frank [20], beading-induced changes in cellmembrane morphology are sufficient to significantly hinder water mobility and thereby decrease the apparent diffusion coefficient; it is recommended to account for this and allow axon diameter variation. Accounting for all these observations, we propose an algorithm relying on a six-fold strategy to design white matter mimicking numerical phantoms, that do not present the actual limitations of existing phantom design tools
Summary
Diffusion-weighted magnetic resonance imaging (dMRI), sensitized to the diffusive motion of water along the direction of an applied magnetic field gradient, has become a well-established technique to non-invasively probe the cellular organization of tissues in vivo. Diffusion NMR measurements embed some information about the inhibition of particles motion due to the presence of barriers in the local environment, and can be exploited to map some specific microstructural features characterizing the brain white matter ultrastructure at cellular scales. Some OGSE studies have reported that, at frequencies below 400 Hz, the OG-measured extra-axonal diffusivity transverse to axons in white matter is linearly dependent on the frequency of the employed OGSE sequence [2], whereas state-of-the art multi-compartment models of white matter relying on PGSE or OGSE sequences usually assume a Gaussian diffusion in the extra-axonal space [3,4,5,6]. A theoretical explanation was given in Burcaw et al [7], where the observed frequency-dependence is interpreted as resulting from the extra-axonal 2D short-range disorder of axonal packings in the plane transverse to white matter fibers.
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