Glymphatic Imaging in Multiple Sclerosis: Microstructural Constraints on DTI-ALPS and Clinical Relevance of gBOLD-CSF Coupling in Relation to Sleep and Disability
- 1Universite Libre de Bruxelles
Abstract
The glymphatic system is the waste clearance pathway in the central nervous system. Although its dysfunction has been associated with several neurological disorders, its role in multiple sclerosis (MS) remains poorly understood. This system is thought to be particularly active during sleep, yet the relationship between sleep metrics and MRI-derived markers of glymphatic activity has been scarcely explored. In this study, we aimed to perform a multimodal magnetic resonance imaging (MRI) assessment of glymphatic function in MS and investigate its association with sleep parameters, clinical disability, disease duration and MRI-derived structural markers. The study included 22 patients (34.3{+/-}10.1 years; 16 female) with relapsing-remitting MS and 26 healthy controls (32.2{+/-}5.7 years; 18 female), all of whom underwent 3.0 Tesla MRI. Glymphatic function was assessed using diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and global blood-oxygen-level-dependent (BOLD) signal-cerebrospinal fluid (CSF) coupling. In addition, sleep micro- and macrostructural features, clinical disability, disease duration, along with mean diffusivity (MD), lateral ventricular, choroid plexus volumes and lesion load were evaluated. Patients showed reduced DTI-ALPS index, though this difference became only a trend after controlling for MD. No significant group differences were observed in global BOLD signal-CSF coupling. However, in patients, the weaker coupling was associated with longer total sleep time, lower arousal index, greater disability and lateral ventricle enlargement, whereas the DTI-ALPS index showed no significant correlations with any of the measures. Together, these findings challenge the assumption that DTI-ALPS can serve as a reliable marker of glymphatic function in demyelinating diseases such as MS, where disease-related alterations in white matter microstructure can confound diffusion-based measures. In contrast, gBOLD-CSF coupling showed associations with sleep, clinical disability and structural changes in patients, despite the absence of a significant group-level difference. This finding suggests that gBOLD-CSF coupling may capture individual variability in glymphatic-related dynamics relevant to sleep and the clinical expression of MS.
Related
- Neuroinflammatory Imaging Biomarkers: Relevance to Multiple Sclerosis and its Therapy
- Strategies for integrating artificial intelligence and cognitive assessment to predict disability progression in relapsing-remitting multiple sclerosis: A model development study
- Noninvasive ultrashort wave neuromodulation enhances glymphatic clearance to alleviate traumatic brain edema and Alzheimer’s pathology
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets
- Modifiable glymphatic-related brain clearance physiology in humans: a critical narrative review of interventional evidence
BibTeX
@misc{sharifpour2026glymphatic,
title = {{Glymphatic Imaging in Multiple Sclerosis: Microstructural Constraints on DTI-ALPS and Clinical Relevance of gBOLD-CSF Coupling in Relation to Sleep and Disability}},
author = {R. Sharifpour and S. Elands and J. Hrabovecky and A. Rovai and X. De Tiege and M. STRAUSS},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755605},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755605v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Glymphatic Imaging in Multiple Sclerosis: Microstructural Constraints on DTI-ALPS and Clinical Relevance of gBOLD-CSF Coupling in Relation to Sleep and Disability
AU - R. Sharifpour
AU - S. Elands
AU - J. Hrabovecky
AU - A. Rovai
AU - X. De Tiege
AU - M. STRAUSS
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755605
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755605v1
AB - The glymphatic system is the waste clearance pathway in the central nervous system. Although its dysfunction has been associated with several neurological disorders, its role in multiple sclerosis (MS) remains poorly understood. This system is thought to be particularly active during sleep, yet the relationship between sleep metrics and MRI-derived markers of glymphatic activity has been scarcely explored. In this study, we aimed to perform a multimodal magnetic resonance imaging (MRI) assessment of glymphatic function in MS and investigate its association with sleep parameters, clinical disability, disease duration and MRI-derived structural markers. The study included 22 patients (34.3{+/-}10.1 years; 16 female) with relapsing-remitting MS and 26 healthy controls (32.2{+/-}5.7 years; 18 female), all of whom underwent 3.0 Tesla MRI. Glymphatic function was assessed using diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and global blood-oxygen-level-dependent (BOLD) signal-cerebrospinal fluid (CSF) coupling. In addition, sleep micro- and macrostructural features, clinical disability, disease duration, along with mean diffusivity (MD), lateral ventricular, choroid plexus volumes and lesion load were evaluated. Patients showed reduced DTI-ALPS index, though this difference became only a trend after controlling for MD. No significant group differences were observed in global BOLD signal-CSF coupling. However, in patients, the weaker coupling was associated with longer total sleep time, lower arousal index, greater disability and lateral ventricle enlargement, whereas the DTI-ALPS index showed no significant correlations with any of the measures. Together, these findings challenge the assumption that DTI-ALPS can serve as a reliable marker of glymphatic function in demyelinating diseases such as MS, where disease-related alterations in white matter microstructure can confound diffusion-based measures. In contrast, gBOLD-CSF coupling showed associations with sleep, clinical disability and structural changes in patients, despite the absence of a significant group-level difference. This finding suggests that gBOLD-CSF coupling may capture individual variability in glymphatic-related dynamics relevant to sleep and the clinical expression of MS.
ER -