Monte Carlo Simulations of Water Exchange Through Myelin Wraps: Implications for Diffusion MRI

Diffusion magnetic resonance imaging (dMRI) yields parameters sensitive to brain tissue microstructure. A structurally important aspect of this microstructure is the myelin wrapping around the axons. This paper investigated the forward problem concerning whether water exchange via the spiraling structure of the myelin can meaningfully contribute to the signal in dMRI. Monte Carlo simulations were performed in a system with intra-axonal, myelin, and extra-axonal compartments. Diffusion in the myelin was simulated as a spiral wrapping the axon, with a custom number of wraps. Exchange (or intra-axonal residence) times were analyzed for various number of wraps and axon diameters. Pulsed gradient sequences were employed to simulate the dMRI signal, which was analyzed using different methods. Diffusional kurtosis imaging analysis yielded the radial diffusivity (RD) and radial kurtosis (RK), while the two-compartment Karger model yielded estimates the intra-axonal volume fraction (v(ic)) and exchange time (tau). Results showed that tau was on the sub-second level for geometrieswith axon diameters below 1.0 mu m and less than eight wraps. Otherwise, exchangewas negligible compared to typical experimental durations, with tau of seconds or longer. In situations where exchange influenced the signal, estimates of RK and v(ic) increasedwith the number of wraps, while RD decreased. tau estimates from simulated signals were in agreement with predicted ones. In conclusion, exchange through spiraling myelin permits sub-second tau for small diameters and low number of wraps. Such conditions may arise in the developing brain or in neurodegenerative disease, and thus the results could aid the interpretation of dMRI studies.