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Extending the ALPS index: Associating whole-brain patterns with glymphatic-related diffusion metrics in multiple
Sascha D Santaniello1, Gabriel Gonzalez-Escamilla2, Markus Janko1
1Department of Neuroradiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Multiple Sclerosis and Related Disorders
|November 16, 2025
Summary
This study introduces Glymphatic Association Mapping (GAM) to assess the brain's waste clearance system in Multiple Sclerosis (MS). GAM reveals widespread glymphatic system impairment and tissue damage, particularly in the basal ganglia and thalamus, in MS patients.
Area of Science:
- Neuroimaging
- Neuroinflammation
- Cerebrospinal fluid dynamics
Background:
- The glymphatic system (GS) clears brain waste but is impaired in neuroinflammatory diseases like Multiple Sclerosis (MS).
- Current non-invasive methods to evaluate GS function are spatially limited, primarily to periventricular areas.
- A novel approach is needed to expand the spatial assessment of GS in vivo.
Purpose of the Study:
- To develop and validate a new method, Glymphatic Association Mapping (GAM), for spatially extended, non-invasive evaluation of the glymphatic system.
- To investigate the association between GAM and diffusion tensor imaging (DTI) metrics (FA, ADC) in healthy controls (HC) and MS patients.
- To explore the relationship between GAM and clinical parameters in MS.
Main Methods:
- Retrospective analysis of T1- and diffusion-weighted MRI data from 165 MS patients and 57 healthy controls (HC).
- Automatic calculation of the periventricular DTI-based index of the glymphatic system (DTI-ALPS).
- Determination of Glymphatic Association Mapping (GAM) by correlating DTI-ALPS with voxel-level FA and ADC values.
Main Results:
- GAM distribution differed significantly between HC and MS patients, with broader distribution in relapsing-remitting MS (RRMS).
- GAM-FA in RRMS patients correlated with impaired glymphatic function and tissue damage in the basal ganglia and thalamus.
- Lower DTI-ALPS values were associated with increased age, lesion volume, and disease duration in MS patients.
Conclusions:
- The developed GAM method demonstrates widespread associations between glymphatic system impairment and tissue damage in MS.
- The observed GAM overlap in the basal ganglia and thalamus provides mechanistic support for previous pathological findings in these brain regions.
- GAM offers a promising tool for a more comprehensive, spatially extended assessment of glymphatic dysfunction in neurological conditions.
