Glymphatic System Dysfunction and DTI along the Perivascular Space in Traumatic Brain Injury: A Systematic Review and Meta-Analysis

BACKGROUND: The glymphatic system, essential for metabolic waste clearance and brain homeostasis, is vulnerable to disruption following traumatic brain injury (TBI). There is a pressing need for practical and robust methods to assess glymphatic function after TBI, as well as for other neurologic disorders. Diffusion tensor imaging along the perivascular space (DTI-ALPS) might have value in quantifying glymphatic dysfunction. PURPOSE: Our aim was to consolidate existing evidence to determine differences in DTI-ALPS values between TBI patients and healthy controls (HCs). DATA SOURCES: All studies utilizing the DTI-ALPS index and reporting its mean and standard deviation in both TBI patients and healthy controls were identified through searches of PubMed, Embase, Scopus, and Web of Science from inception to August 8, 2025. STUDY SELECTION: Eleven studies comprising 694 patients with TBI, and 503 HCs were included. DATA ANALYSIS: Meta-analysis was conducted using a random-effects model. Standardized mean differences (Hedges’ g) were used as the effect size measure. Pooled correlations between DTI-ALPS indices and demographic variables were evaluated. Heterogeneity was assessed using Higgins’ I2 statistic. Subgroup analyses, meta-regression, and sensitivity analyses were performed to identify potential sources of heterogeneity, and publication bias was examined using funnel plots and Begg’s test. DATA SYNTHESIS: DTI-ALPS values were found to be significantly reduced in TBI patients compared to HCs (Hedges’ g = -0.77; 95% CI: -1.38 to -0.15; I2=93%). DTI-ALPS showed no significant correlation with age or Glasgow Coma Scale scores. Subgroup analyses revealed larger effect sizes in single-shell studies and those with higher methodological rigor. Meta-regression showed a larger decrease in DTI-ALPS values in TBI patients over time (β=-0.01, p=0.03). No substantial publication bias was detected (p=0.12). LIMITATIONS: Our meta-analysis is limited by substantial heterogeneity and the small number of included studies. CONCLUSIONS: TBI is associated with significantly reduced DTI-ALPS values, with more prominent deteriorations over the long term, supporting its potential as a biomarker of glymphatic impairment. However, methodological heterogeneity emphasizes the need for standardized protocols and longitudinal studies to establish clinical utility.