Orientation Dependence of R2' in White Matter: Digital Characterization, Modelling and Implications for Studying Brain Physiology

PurposeR2*, the transverse relaxation rate, reflects local magnetic field inhomogeneities from susceptibility differences with R2, the reversible component sensitive to blood oxygenation. Orientation dependence of R2 and R2* in white matter (WM) are attributed primarily to myelin, with vascular contributions to R2 uncharacterized. This study examined WM R2 orientation dependence, evaluated existing models, and developed an improved model combining myelin and blood. MethodsSimulations used BOLDswimsuite with 2D WM voxels (5,000 fibres). Spin-echo (TE = 70ms) and gradient-echo (TE = 35ms) signals were simulated across 30 fibre orientations (0{degrees}-90{degrees}). R2' was calculated as R2* - R2. Oxygenation, cerebral blood volume (CBV), vessel size, and vessel geometry were varied. Four published models and a novel Myelin-Blood model were fitted to R2' data and compared using R2 and RMSE. ResultsR2 and R2* showed strong orientation dependence. Parallel and mixed vessel geometries produced greater R2' amplitude and orientation dependence than random geometries; decreasing oxygenation and increasing CBV amplified orientation effects. Vessel size altered peak locations. Existing vascular models performed poorly, and the Empirical Myelin Model erred near the magic angle. The Myelin-Blood model provided near-perfect fits (mean R2 = 0.999, RMSE = 0.007 Hz), reducing RMSE by ~74%. DiscussionWM R2' cannot be explained by vascular or myelin effects alone. Myelin is the primary determinant of orientation dependence, but vascular contributions were evident near the magic angle and low oxygenation. The Myelin-Blood model improves WM R2 characterisation and may reduce orientation-dependent bias and improve interpretation of WM BOLD fMRI signals.