White Matter Geometry Confounds Diffusion Tensor Imaging Along Perivascular Space (DTI-ALPS) Measures

Area of Science:

• Neuroimaging
• White Matter Microstructure
• Glymphatic System Function

Background:

• The perivascular space (PVS) is crucial for brain fluid exchange and waste clearance via the glymphatic system.
• Diffusion tensor imaging along the perivascular space (DTI-ALPS) is a proposed noninvasive marker for PVS diffusion.
• ALPS measures assume radial symmetry and interpret deviations as PVS contributions, but specificity is debated.

Purpose of the Study:

• To systematically evaluate potential biases in ALPS-derived measures.
• To investigate the influence of white matter microstructure on ALPS indices.
• To assess the validity of ALPS as a specific marker of glymphatic function.

Main Methods:

• Analysis of high-resolution, multishell diffusion MRI data from the Human Connectome Project (HCP).
• Examination of radial asymmetry prevalence, crossing fiber effects, axonal geometry impacts, and vascular alignment.
• Utilized high-field imaging and advanced diffusion modeling approaches.

Main Results:

• Widespread radial asymmetry in white matter persists even at high b-values, indicating axonal geometry's dominant role.
• Crossing fibers and axonal dispersion/undulations significantly inflate ALPS indices, introducing systematic asymmetry.
• Heterogeneous medullary vein orientation challenges the assumption of consistent PVS-vasculature alignment in ALPS regions.

Conclusions:

• ALPS indices are substantially influenced by white matter microstructure, not solely by PVS diffusion.
• ALPS measures may primarily reflect axonal geometry rather than directly indicating glymphatic function.
• Future interpretations of ALPS as a glymphatic biomarker require accounting for anatomical complexities and advanced modeling.