Vascular permeability mediates contralateral glymphatic dysfunction across glioma grades and IDH status.

PURPOSE: Bilateral hemisphere-specific glymphatic dysfunction (GS) is a prevalent feature in glioma patients and may be affected by vascular permeability. However, the mechanisms by which tumor-related vascular permeability influences tumor-ipsilateral or contralateral glymphatic function remain unclear. This study aimed to elucidate how tumor-related vascular permeability modulates ipsilateral or contralateral glymphatic function in glioma patients, stratified by WHO grades and IDH mutation statuses, employing a novel integration of noninvasive diffusion tensor imaging along the perivascular space (DTI-ALPS) and dynamic contrast-enhanced MRI (DCE-MRI). METHODS: A total of 104 patients with histologically confirmed gliomas and 42 age- and sex-matched healthy controls were included. Glymphatic function was assessed bilaterally using DTI-ALPS, while vascular permeability was evaluated via DCE-MRI parameters (Ktrans, Ve, iAUC). Multiple statistical approaches were used to examine the relationships among glioma clinical characteristics (WHO grade and IDH status), DCE-MRI parameters, and bilateral ALPS indices. Mediation models examined the mediating role of vascular permeability in both hemispheres. RESULTS: Glioma patients showed bilaterally reduced ALPS indices versus controls (p < 0.001), with contralateral higher than ipsilateral (p < 0.05). Lower ALPS indices associated with high-grade and IDH-wild-type tumors (p < 0.01). Ktrans correlated negatively with contralateral ALPS (β = -0.329, p = 0.002) and statistically mediated the relationship between tumor grade (23.4%) / IDH status (21.7%) and contralateral impairment (p < 0.01). CONCLUSIONS: Glioma patients exhibit bilateral glymphatic dysfunction, most severe in high-grade or IDH-wild-type tumors. Ktrans, reflecting blood brain barrier permeability, statistically mediated the association between tumor grade / IDH status and contralateral glymphatic impairment, with no such mediation observed ipsilaterally.