Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) as an Imaging Biomarker of Glymphatic Dysfunction in Gliomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is an noninvasive MRI biomarker of perivascular/glymphatic diffusivity. Although individual studies suggest that gliomas are associated with disrupted glymphatic function, the magnitude and consistency of DTI-ALPS alterations have not been systematically evaluated. PURPOSE: To systematically evaluate DTI-ALPS-index differences between glioma patients and healthy controls and to investigate associations with tumor grade, Isocitrate Dehydrogenase(IDH) mutation status, and tumor laterality. DATA SOURCES: PubMed, Embase, and Scopus were searched from database inception through May 2026. STUDY SELECTION: Human studies reporting DTI-ALPS-index values in glioma patients and healthy controls were included. DATA ANALYSIS: Mean differences(MDs) were pooled using random-effects inverse-variance meta-analysis. DATA SYNTHESIS: Seven comparator cohorts including 628 glioma patients and 309 healthy controls were included. Glioma patients demonstrated significantly lower ALPS-index values than healthy controls(MD, -0.18; 95% CI, -0.23 to -0.14; P<.00001; I2=70%). Lower-grade gliomas had higher ALPS-index values than higher-grade gliomas(MD, 0.11; 95% CI, 0.01-0.21; P=.03; I2=96%). The primary differences between IDH-mutant and IDH-wildtype gliomas(MD, 0.09; 95% CI, -0.01 to 0.18; P=.07; I2=95%) and between tumor-ipsilateral and contralateral hemispheres(MD, -0.04; 95% CI, -0.08 to 0.01; P=.12; I2=78%) were not statistically significant. Exploratory sensitivity analyses excluding one influential cohort yielded statistically significant grade-, IDH-, and laterality-based differences with reduced heterogeneity; however, these findings were dependent on cohort exclusion and should be considered hypothesis-generating. LIMITATIONS: The evidence is limited by few studies, high heterogeneity, methodological differences in DTI-ALPS measurement, and observational study designs, with some subgroup results changing when individual cohorts are excluded. CONCLUSIONS: Gliomas are associated with reduced DTI-ALPS-index values compared with healthy controls, indicating impaired perivascular/glymphatic diffusivity. However, associations with tumor grade, IDH status, and laterality remain uncertain due to heterogeneity and sensitivity to individual studies. DTI-ALPS is a promising noninvasive biomarker of disease-associated brain-fluid transport dysfunction, but requires prospective validation, including in studies of transport-modulating interventions.