Measuring compartmental T2-orientational dependence in human brain white matter using a tiltable RF coil and diffusion-T2 correlation MRI

Abstract

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 . 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 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 . A dependence of (compartmental) on the fibre orientation w.r.t. 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 orientation-dependence is dominated by magnetic susceptibility effects (presumably from the myelin sheath) while the weaker intra-axonal 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 - and diffusion-MRI data analysis, where the effect of head-orientation in the scanner is commonly ignored.

Orientation dependent proton transverse relaxation in the human brain white matter: The magic angle effect on a cylindrical helix

“…Perhaps, an extreme “demyelination” case would be elongated cellular constituents (e.g., microtubules and neurofilaments) in an intra-axonal space, revealing a considerably reduced compared to that in an extra-axonal space as shown in Supplementary Figure S4. 7 On the other hand, a considerably increased was measured at room temperatures on formalin-fixed WM specimens embedded in an agarose gel at higher fields (≥7T). 40, 41 Moreover, the measured from semisolid CH2 groups in WM was much larger than that from dynamically ordered water close to the phospholipid bilayer surface (Table 1).…”

“…Here, θ is the angle between an axon fiber and B 0 , A i and B i ( i = 1,2,3) the model parameters (i.e., trigonometric function coefficients). As revealed recently, 7, 17 both functions are mathematically equivalent albeit with different coefficients. More importantly, these coefficients are not mutually independent as cos4 θ (or sin 4 θ ) can be expressed by cos2θ (or sin 2 θ ) and vice versa; thus, any proposed biophysical interpretations of fitted model parameters will become ambiguous.…”

“…7,8 Although it has been long before documented in the peripheral nervous system, 9 MAE still remains elusive in the human brain white matter (WM) despite that extensive research has been performed in the past two decates. [10][11][12] Based on the standard MAE function, . [12][13][14][15] Further, MAE is assumed exclusively involving collagen that is hardly found in the human brain parenchyma.…”

“…For instance, myelinated axons in the human brain white matter (WM) are anisotropic and inhomogeneous in nature and water proton longitudinal (i.e., R 1 =1/ T 1 ) and transverse (i.e., R 2 =1/ T 2 ) relaxation rates have been revealed depending on orientations of axon fibers although the reported R 1 relaxation anisotropy is much smaller than that of R 2 . 4–7…”

“…As both stemmed from thermally driven Brownian motion, molecular translational diffusion and rotational diffusion are intimately linked, 7, 27, 28 with the former probed by DTI and the latter by MR relaxation measurements. To our knowledge, no direct connection exists between the two different measurements for studying the same anisotropic microstructures in WM.…”