MyCaliber: Axon diameter mapping from myelin water diffusion -- Theory, Resolution Limit, and Monte Carlo simulations

Motivation: Probing diffusion in myelin water using diffusion-weighted T1-/T2-selective MRI acquisitions enables to non-invasively measure myelinated axon radius. Its application for in vivo measurements requires validation through diffusion simulations. Goal(s): To propose the theory of myelin water diffusion in wide-gradient-pulse sequence and validate its applicability to axon radius estimation via Monte Carlo simulations. Approach: We derived the theory using Gaussian-phase-approximation. We validated the proposed model by performing diffusion simulations in infinitely thin cylindrical surfaces or concentric cylindrical layers of finite thickness. Results: Simulation results validated the theory of myelin water diffusivity and axon radius estimation using spherical-mean signals. Impact: Measuring restricted diffusion of myelin water in-between myelin sheaths using diffusion MRI enables to in vivo measure axon radius. Simulation results demonstrated its applicability at SNR≥5 on Connectome 2.0 scanner. The protocol can be adapted for clinically available high-gradient-performance scanners.