Origin of orientation-dependent R₁ (=1/T₁ ) relaxation in white matter

In a recent MRI study, it was shown that the longitudinal relaxation rate, R₁ , in white matter (WM) is influenced by the relative orientation of nerve fibers with respect to the main magnetic field (B₀ ). Even though the exact nature of this R₁ orientation dependency is still unclear, it can be assumed that the origin of the phenomenon can be attributed to the anisotropic and unique molecular environment within the myelin sheath surrounding the axons. The current work investigates the contribution of dipolar induced R₁ relaxation of the myelin associated hydrogen nuclei theoretically and compares the results with the experimentally observed R₁ orientation dependency.

Atomistic molecular dynamics simulations were employed and the R₁ relaxation rate of hydrogen nuclei of a myelin-alike molecular environment was calculated for various orientations of the trajectory sets relative to the B₀ -field. Based on the calculated relaxation rates, the observable R₁ relaxation was simulated for various fiber orientations and fitted to the experimental data using a suitable signal weighting-scheme.

The results obtained show that the R₁ relaxation rate of both solid myelin (SM) and myelin water (MW) depends on the fiber orientation relative to the main B₀ -field. Moreover, employing a realistic signal weighing scheme and tissue characteristics, the theoretically investigated R₁ orientation dependency matches the experimental data well.

The good agreement between theoretical and experimental findings indicates that the R₁ orientation dependency in WM mainly originates from anisotropic dipole-dipole interactions between hydrogen nuclei located within the myelin sheath.