Unraveling glymphatic disruption in brain tumors: Insights from perivascular space network analysis

Brain tumors disrupt the glymphatic system-a critical network for cerebrospinal and interstitial fluid circulation via the perivascular spaces (PVS)-yet the extent and underlying mechanisms of this dysfunction remain poorly defined. In a prospective study, 104 brain tumor patients (40 high-grade gliomas, 26 metastases, and 38 meningiomas) and 30 age- and sex-matched healthy controls underwent advanced MRI assessments to quantify white matter PVS volume fraction (PVSVF-WM), free water fraction (FW-WM), and the DTI-ALPS index. All tumor groups exhibited significantly elevated PVSVF-WM (p < .001) and reduced DTI-ALPS index, indicating PVS dilation and impaired glymphatic function, while FW-WM showed significant group differences, with the lowest values observed in patients with high-grade glioma (p < .001). Tumor volume showed a strong positive correlation with PVSVF-WM (ρ = 0.674, p < .001) and a negative correlation with the DTI-ALPS index (ρ = -0.482, p < .001). Moreover, in gliomas, Ki67 expression correlated positively with PVSVF-WM (ρ = 0.563, p < .001) and negatively with the DTI-ALPS index (ρ = -0.482, p = .002), whereas in metastases, p53 expression correlated positively with the DTI-ALPS index (ρ = 0.569, p = .002). These findings demonstrate that brain tumors alter the PVS network, leading to glymphatic dysfunction, with the degree of disruption being modulated by tumor burden and molecular characteristics. The innovative MRI-based metrics used in this study provide valuable insights into tumor-associated glymphatic alterations and may inform the development of tailored therapeutic interventions.