DTI‐ALPS primarily reflects white matter diffusion dispersion and microstructural heterogeneity in neurodegeneration: Insights from multi‐modal MRI

Sacchi, Luca, Farruggio, Giovanni, Bocca, Giorgio, Carandini, Tiziana, Riz, Milena De, Ghezzi, Laura, Pintus, Manuela, Pietroboni, Anna, Boffa, Giacomo, Scola, Elisa, Triulzi, Fabio, Bozzali, Marco, Galimberti, Daniela, Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456 and Arighi, Andrea 2026. DTI‐ALPS primarily reflects white matter diffusion dispersion and microstructural heterogeneity in neurodegeneration: Insights from multi‐modal MRI. Human Brain Mapping 47 (14) , e70603. 10.1002/hbm.70603

PDF - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB)

Abstract

The glymphatic system facilitates clearance of metabolic waste and pathological proteins from the brain, and its dysfunction has been implicated in neurodegenerative disease. The diffusion tensor imaging–analysis along the perivascular space (DTI-ALPS) has been proposed as a non-invasive MRI marker of glymphatic flow, although its biological specificity remains uncertain. This study aimed to identify the determinants of DTI-ALPS and evaluate whether it primarily reflects white-matter (WM) microstructure rather than glymphatic flow in the context of neurodegeneration. We examined 100 individuals referred to the Memory Clinic of the Policlinico Hospital in Milan for suspected dementia. All participants underwent a 3T-MRI protocol including 3D-T1-weighted and 3D-FLAIR imaging, double-shell diffusion-weighted imaging (b = 1000/2000 s/mm2), and multi-echo gradient-echo sequences for quantitative susceptibility mapping. Within standard DTI-ALPS ROIs, we extracted DTI-ALPS values together with fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MA) at both b-values, as well as neurite orientation and density imaging (NODDI) metrics, particularly the orientation dispersion index (ODI). WM microstructure was further characterized using the T1/FLAIR ratio and diamagnetic component of susceptibility (DCS). DTI-ALPS correlated inversely with MA (r = −0.84 at b = 1000; r = −0.86 at b = 2000) and positively with ODI (r = 0.73). Moderate correlations with the T1/FLAIR ratio and DCS supported sensitivity to WM alterations. Factor analysis indicated that DTI-ALPS clustered with MA and ODI rather than forming a distinct factor, suggesting that DTI-ALPS primarily reflects WM diffusion dispersion and heterogeneity rather than glymphatic flow in the context of neurodegeneration.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Psychology Research Institutes & Centres > Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	Wiley
ISSN:	1065-9471
Date of First Compliant Deposit:	28 September 2026
Last Modified:	28 Sep 2026 15:45
URI:	https://orca.cardiff.ac.uk/id/eprint/189851

Actions (repository staff only)

Edit Item