Exploring radial asymmetry in MR diffusion tensor imaging and its impact on the interpretation of glymphatic mechanisms

Motivation: Researchers have used diffusion tensor imaging along the perivascular space (DTI-ALPS) to investigate glymphatic function, but the influence of white matter properties on the ALPS-index remains unstudied. Goal(s): Establish whether a reduction in the ALPS-index could be influenced by axonal changes. Approach: A key assumption underlying the ALPS-index is that axons demonstrate symmetric radial diffusivities, such that eigenvalue-2 and eigenvalue-3 are equal (λ2=λ3). We investigated this assumption and evaluated λ2/λ3 changes in white matter tracts. Results: Contrary to the DTI-ALPS assumption, widespread radial asymmetry (λ2/λ3≈1.5) was observed within all white matter tracts, the extent of which decreased with aging and neurodegeneration. Impact: This study unveils widespread radial asymmetry of white matter tracts — a phenomenon that has been overlooked in DTI studies. The results provide evidence of axonal contributions to the ALPS-index, prompting researchers to consider axonal influences when interpreting this metric.