Simulations on the influence of myelin water in diffusion-weighted imaging

Abstract

While myelinated axons present an important barrier to water diffusion, many models used to interpret DWI signal neglect other potential influences of myelin. In this work, Monte Carlo simulations were used to test the sensitivity of DWI results to the diffusive properties of water within myelin. Within these simulations, the apparent diffusion coefficient (Dapp) varied slowly over several orders of magnitude of the coefficient of myelin water diffusion (Dm), but exhibited important differences compared to Dapp values simulated that neglect Dm (=0). Compared to Dapp, the apparent diffusion kurtosis (Kapp) was generally more sensitive to Dm. Simulations also tested the sensitivity of Dapp and Kapp to the amount of myelin present. Unique variations in Dapp and Kapp caused by differences in the myelin volume fraction were diminished when myelin water diffusion was included. Also, expected trends in Dapp and Kapp with experimental echo time were reduced or inverted when accounting for myelin water diffusion, and these reduced/inverted trends were seen experimentally in ex vivo rat brain DWI experiments. In general, myelin water has the potential to subtly influence DWI results and bias models of DWI that neglect these components of white matter.

Effect of myelin water exchange on DTI‐derived parameters in diffusion MRI: Elucidation of TE dependence

“…The myelin sheath is reported to account for 50% of dry weight of brain, and myelin water fraction takes up 7–16% of total water in normal white matter . In some previous Monte Carlo models that focused on the geometrical characteristics, myelin water was often not considered , while some recent studies have considered myelin to investigate the relaxation properties of tissue . In this study, to mimic myelinated axons more comprehensively, a compartment of myelin water with its own diffusivity and T 2 values was incorporated into the model (Fig.…”

“…Several assumptions were made in the model based on the related literature of cellular structures and numerical simulations : The tissue was separated into three compartments by two concentric cylinders of infinite length. The intra‐axonal compartment was represented by the inner cylinder, the myelin sheath by the volume between inner and outer cylinders, and the extra‐axonal compartment was represented by the space outside the cylinders.…”

“…Lin et al simulated the changes of DTI‐derived parameter due to different pathologies at cellular level after traumatic brain injury. Very recently, Harkins and Does proposed a myelinated axon model and investigated the subtle influence of myelin water on diffusion‐weighted signal.…”

Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder

“…Though one may prefer to include a third compartment, which is strongly restricted in all directions to represent water trapped inside cell bodies or other small compartments, recent studies using high b ‐values and isotropic diffusion weighting suggested that the contribution from stationary water would be below the detection limit. Also, though the water within myelin is often neglected in diffusion models because of its short T 2 relaxation time, recent studies have suggested a subtle but significant contribution from the finite exchange with the myelin water pool. The exchange between the two compartments is negligible. The intra‐neurite pre‐exchange lifetime in normal myelinated white matter is reportedly about a second, and is regarded as sufficiently long compared with the diffusion time. The diffusion time ( t ) is sufficiently long that diffusion within each compartment can be approximated as Gaussian .…”

“…Though one may prefer to include a third compartment, which is strongly restricted in all directions to represent water trapped inside cell bodies or other small compartments, 22 recent studies using high b-values 45 and isotropic diffusion weighting 46 suggested that the contribution from stationary water would be below the detection limit. Also, though the water within myelin is often neglected in diffusion models because of its short T 2 relaxation time, recent studies 47,48 have suggested a subtle but significant contribution from the finite exchange with the myelin water pool.…”