Measuring compartmental [Formula: see text]-orientational dependence in human brain white matter using a tiltable RF coil and diffusion- [Formula: see text] correlation MRI

The anisotropy of brain white matter microstructure manifests itself in orientational-dependence of various MRI contrasts, and can result in significant quantification biases if ignored. Understanding the origins of this orientation-dependence could enhance the interpretation of MRI signal changes in development, ageing and disease and ultimately improve clinical diagnosis. Using a novel experimental setup, this work studies the contributions of the intra- and extra-axonal water to the orientation-dependence of one of the most clinically-studied parameters, apparent transverse relaxation [Formula: see text]. Specifically, a tiltable receive coil is interfaced with an ultra-strong gradient MRI scanner to acquire multidimensional MRI data with an unprecedented range of acquisition parameters. Using this setup, compartmental [Formula: see text] can be disentangled based on differences in diffusional-anisotropy, and its orientation-dependence further elucidated by re-orienting the head with respect to the main magnetic field [Formula: see text]. A dependence of (compartmental) [Formula: see text] on the fibre orientation w.r.t. [Formula: see text] was observed, and further quantified using characteristic representations for susceptibility- and magic angle effects. Across white matter, anisotropy effects were dominated by the extra-axonal water signal, while the intra-axonal water signal decay varied less with fibre-orientation. Moreover, the results suggest that the stronger extra-axonal [Formula: see text] orientation-dependence is dominated by magnetic susceptibility effects (presumably from the myelin sheath) while the weaker intra-axonal [Formula: see text] orientation-dependence may be driven by a combination of microstructural effects. Even though the current design of the tiltable coil only offers a modest range of angles, the results demonstrate an overall effect of tilt and serve as a proof-of-concept motivating further hardware development to facilitate experiments that explore orientational anisotropy. These observations have the potential to lead to white matter microstructural models with increased compartmental sensitivity to disease, and can have direct consequences for longitudinal and group-wise [Formula: see text]- and diffusion-MRI data analysis, where the effect of head-orientation in the scanner is commonly ignored.