Synopsis

Myelin is essential component for complex motor, sensory and cognition function.¹ Among many quantitative magnetic resonance imaging (MRI) techniques investigating myelin structure, direct MR parameter influenced by the myelin thickness is rarely investigated.¹ Here, we study the effect of myelin thickness on R₂, R₂* and susceptibility using the finite perturber method (FPM)-based simulation and post-mortem aging rat brains. It is observed from simulations that both myelin thickness and myelin volume fraction (MVF) affects R₂ and R₂* values, whereas the phase change (QSM) showed a significant change only by the change of MVF. In preliminar experiments, consistent results were observed.

Purpose

Methods

FPM-based Monte Carlo simulation was implemented using MATLAB (Mathworks, Natick, MA) on an R2017a environment.³ Simulation parameters: number of repetition = 2, 600x600x600 matrix with voxel size = 0.2μm, number of protons = 5.4x10⁷, magnetic field strength = 7T, spin echo time (TE) = 8, 16, 32, 64, 100ms and gradient echo TE = 12, 24, 36, 48, 60ms with unit time = 0.2ms. Myelin geometry parameters: axon radius = 1 to 5μm with fixed g-ratio = 0.8 (so, myelin thickness = 0.25 to 1.25μm), MVF = 5% and 15% with Δχ = -0.26ppm (SI unit).⁴ Cylinders are randomly distributed along y-axis direction.

To observe the phase variation of the voxels around the structure geometry, we setup the 200x200x200 matrix in the center of the original matrix and constructed another simulation geometry with the same parameters.

Since both myelin thickness and MVF are known to increase with aging for rodents, we setup the aging-rat model study.⁵ 6 weeks (n=3), 4 months (n=3), and 20 months (n=3) old groups female Spraque Dawley rats were used to identify age-related myelin thickness changes. All of brains were fixed and stored in formaldehyde solution. Selected white matter region was corpus callosum for the analysis.

T₂-weighted multi-slice-multi-echo (MSME) images and T₂*-weighted multi-gradient-echo (MGE) images were acquired at 7T MRI scanner (Bruker), and quantitative susceptibility mapping (QSM) were computed from the MGE phase data with non-skull region of interest (ROI). MSME parameters: repetition time (TR) = 4000ms, TE = 8 to 384ms with echo spacing 8ms. MGE parameters: TR = 4000ms, TE = 2.7 to 50.3ms with echo spacing 3.4ms. Both sequences used matrix size = 256x256 and field of view (FOV) = 25x25mm².

Results

The simulation geometry and ΔB maps according to MVF and thickness are shown in figure 1. Figure 2 shows the representative results of R₂, R₂* mapping and QSM of each one of 6 weeks, 4 months, and 20 months rat brains. At the corpus callosum region, both R₂, R₂* and susceptibility values have shown significant changes with age (Fig 2c-2k).

According to the simulation results, R₂* values were observed to linearly increase but R₂ values were observed to increase and saturate at some specific thickness, when both values were plotted with respect to increasing myelin thickness (Fig 3a-3b). This tendency was similarly observed in the rat experimental R₂ and R₂* results (Fig 3c-3d). At the corpus callosum, R₂* values were observed to linearly increase with aging, but R₂ values have significantly increased in the interval from 6 weeks to 4 months and the increasement was less in the interval from 4 months to 20 months (Fig 3c-3d). As the MVF increased in the simulations, the values of R₂ and R₂* have increased maintaining similar behaviors with increasing thickness (Fig 3a-3d). In the case of QSM, although the standard deviation is large, it has shown decreasing magnetic susceptibility with aging corpus callosum, which is the signature of enlarging MVF (Fig 3e).

Figure 4 shows the changes of ΔB and phase maps by variations of myelin thickness and MVF. In case of ΔB maps, the field is affected by both myelin thickness and MVF changes (Fig 4a-4c). However, the phase maps are sensitive to changes in MVF (Fig 4d-4e), not to myelin thickness (Fig 4e-4f).

Conclusion and discussion

We can see through the simulation results that both the myelin thickness and MVF affect to R₂ and R₂* values (Fig 3a-3b, 4a-4c), and these tendencies were consistent with the aging-rat study (Fig 3c-3d). Also, simulation results show that the change of phase field occurs only by the change of MVF regardless of the axon thickness (Fig 4). These results suggest that if the effects of relaxation and phase changes are mutually combined, the MVF effect may be able to offset, then information on myelin thickness may be obtained using MRI with further validations.

Acknowledgements

References

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