Diffusion MRI yields parameters sensitive to brain tissue microstructure. A structurally important aspect of this microstructure is the myelin wrapping around the axons. This study 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 of 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 Kärger model yielded estimates of the intra-axonal volume fraction (νic) and exchange time (τ). Results showed that τ was on the sub-second level for geometries with axon diameters below 1.0 μm and less than eight wraps. Otherwise, exchange was negligible compared to typical experimental durations, with τ of seconds or longer. In situations where exchange influenced the signal, estimates of RK and νic increased with the number of wraps, while RD decreased. τ estimates from simulated signals were in agreement with predicted ones. In conclusion, exchange through spiraling myelin permits sub-second τ 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.
Click here for instructions to update publications.