Bozzali, M. | Search bioRxiv

bioRxiv2025

DTI-ALPS PRIMARILY REFLECTS WHITE MATTER DIFFUSION DISPERSION AND MICROSTRUCTURAL HETEROGENEITY IN NEURODEGENERATION: INSIGHTS FROM MULTI-MODAL MRI

1.1.1 BackgroundThe 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. 1.2 MethodsWe 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/mm{superscript 2}), 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). 1.3 Results and conclusionsDTI-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. KeypointsO_LIDTI-ALPS links strongly with mode of anisotropy at high b-values and orientation dispersion, indicating crossing-fibers loss C_LIO_LIDTI-ALPS is moderately associated to T1/FLAIR ratio and diamagnetic susceptibility values, reflecting microstructural WM changes C_LIO_LIDTI-ALPS reflects primarily WM features and may lack specificity for glymphatic flow in the context of neurodegeneration. C_LI

neuroscience↗

bioRxiv2018

Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Macroscale white matter pathways form the infrastructure for large-scale communication in the human brain, a prerequisite for healthy brain function. Conversely, disruptions in the brains connectivity architecture are thought to play an important role in a wide range of psychiatric and neurological brain disorders. Here we show that especially connections important for global communication and network integration are involved in a wide range of brain disorders. We report on a meta-analytic connectome study comprising in total 895 patients and 1,016 controls across twelve neurological and psychiatric disorders. We extracted disorder connectome fingerprints for each of these twelve disorders, which were then combined into a cross-disorder disconnectivity involvement map, representing the involvement of each brain pathway across brain disorders. Our findings show connections central to the brains infrastructure are disproportionally involved across a wide range of disorders. Connections critical for global network communication and integration display high disturbance across disorders, suggesting a general cross-disorder involvement and importance of these pathways in normal function. Taken together, our cross-disorder study suggests a convergence of disconnectivity across disorders to a partially shared disconnectivity substrate of central connections.

neuroscience↗