Mechanical Properties of White Matter Tracts in Aging Assessed via Anisotropic MR Elastography

Abstract Magnetic resonance elastography (MRE) is a promising neuroimaging technique to probe tissue microstructure through mechanical properties, such as stiffness, and which has revealed widespread softening in the aging brain and in neurological disorders. Traditional MRE approaches assume mechanical isotropy. However, white matter is known to be anisotropic from aligned, myelinated axonal bundles, which can lead to uncertainty in mechanical property estimates in these areas from isotropic MRE. Recent advances in anisotropic MRE now allow for estimation of shear and tensile anisotropy, along with substrate shear modulus, in white matter tracts. The objective of this study was to investigate age-related differences in anisotropic mechanical properties in human brain white matter for the first time. Anisotropic mechanical properties in major white matter tracts were found to be significantly lower in older adults (mean 68.5 ± 5.5 years; range 57-82) compared to young adults (mean 25.4 ± 2.2 years; range 22-30), with average property differences ranging between 0.028-0.111 for shear anisotropy and between 0.140-0.350 for tensile anisotropy. Stiffness perpendicular to the axonal fiber direction was significantly lower in older adults in the anterior thalamic radiation (2.78±0.21 vs. 3.00±0.15 kPa; p 0.001) and forceps minor (2.61±0.23 vs. 2.94±0.23 kPa; p 0.001) fibers, while stiffness parallel to fiber direction was lower in most tracts with an average difference between groups of 0.36 kPa or 12.1%, reflected by the widespread lower shear anisotropy observed in older adults. Comparing anisotropic MRE metrics with multiple measures of white matter microstructure from diffusion tensor imaging using tract based spatial statistics, we observed anisotropic MRE measures further differentiated young and older adults in a logistic regression analysis, and widespread differences between mechanical anisotropy and DTI parameters were observed in the voxel-wise analysis. These results suggest that aging effects seen in anisotropic MRE measures are not overly redundant with aging effects on diffusion measures, and the addition of anisotropic MRE measures could further describe differences between the white matter of young and older adult populations. Anisotropic MRE provides a new tool for studying white matter microstructure with mechanical properties in aging and neurodegeneration.