Association between perivascular diffusion and white matter microstructural integrity, free water, Aβ burden, and...

Area of Science:

• Neuroimaging
• Neuroscience
• Biomedical Engineering

Background:

• Perivascular diffusion imaging is crucial for assessing the glymphatic system (GS).
• Traditional diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is limited by microstructural alterations.
• Diffusion kurtosis imaging analysis along the perivascular space (DKI-ALPS) offers a potentially more robust method.

Purpose of the Study:

• To compare cross-sectional and longitudinal DKI-ALPS and DTI-ALPS.
• To investigate associations with white matter (WM) integrity, free water (FW), amyloid-beta (Aβ) burden, and cognitive impairment (CI).

Main Methods:

• 128 healthy controls (HCs) and 83 individuals with CI underwent multi-shell diffusion-weighted MRI (dMRI).
• Quantified DTI-ALPS and DKI-ALPS for GS function, peak width of skeletonized mean diffusivity (PSMD) for WM integrity, and FW-WM for extracellular fluid.
• Generalized linear models (GLMs) and functional principal component analysis (FPCA) were used to analyze group differences and longitudinal trajectories.

Main Results:

• CIs showed significantly lower DTI-ALPS and DKI-ALPS than HCs.
• Both DTI-ALPS and DKI-ALPS correlated negatively with PSMD and FW-WM.
• FPCA revealed distinct longitudinal trajectories between HCs and CIs, with DKI-ALPS trajectories showing stronger correlations with Aβ burden and cognitive performance.

Conclusions:

• DKI-ALPS provides a more accurate assessment of GS function than DTI-ALPS.
• Longitudinal DKI-ALPS trajectories are strongly associated with Aβ burden and cognitive decline, suggesting potential as a biomarker.