Probing diffusion in myelin water using diffusion-weighted T1-/T2-selective MRI acquisitions enables noninvasive measurement of myelinated axon diameter. Its application for in vivo measurements requires numerical verification through diffusion simulations. Here, we propose the theory of myelin water diffusion as measured with a diffusion MRI pulse sequence with wide gradient pulses using the Gaussian phase approximation. We establish its applicability to axonal diameter mapping via Monte Carlo simulations in either infinitely thin cylindrical surfaces or concentric cylindrical shells of finite thickness, mimicking the micro-geometry of myelin sheaths. The estimated diameters are shown to be weighted more toward outer than inner calibers. Simulation results evaluate the theory of myelin water diffusion and axon diameter estimation using spherical mean diffusion signals, demonstrating its applicability at signal-to-noise ratio above 20 on the Connectome 2.0 MRI scanner equipped with maximum gradient strength of 500 mT/m and slew rate of 600 T/m/s. Measuring restricted diffusion of myelin water in-between myelin sheaths using diffusion MRI allows one to measure myelinated axon diameters in vivo. The protocol can potentially be adapted for clinically available high-gradient performance scanners.
Lee et al. (Thu,) studied this question.