A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multiparametric MRI

Abstract Purpose: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage by leveraging advanced MRI techniques to explore the relationships among tumor characteristics, glymphatic function, and aquaporin-4 (AQP4) expression levels. Experimental Design: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and multiparametric MRI for quantitative brain mapping. Tumor and peritumor tissues were analyzed for AQP4 expression levels via immunofluorescence. Correlations among MRI parameters, glymphatic function (DTI-ALPS index), and AQP4 expression levels were statistically assessed. Results: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), patients with brain tumor exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; P = 0.001) and increased cerebrospinal fluid volume (201.376 cm³ vs. 115.957 cm³; P = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: −0.715, P < 0.001), whereas AQP4 expression levels correlated positively with peritumoral brain edema volume (r: 0.989, P < 0.001) and negatively with proton density in peritumoral brain edema areas (ρ: −0.506, P < 0.001). Conclusions: Our findings highlight the interplay among tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, demonstrating the utility of DTI-ALPS and multiparametric MRI in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system. See related commentary by Surov and Borggrefe, p. 4813