Abstract
ObjectivesRodent experiments have provided some insights into the changes of glymphatic function associated with glioma growth. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with glioma. We aimed to investigate the factors associated with glymphatic function changes in patients with glioma.Materials and MethodsA total of 201 glioma patients (mean age = 47.4 years, 116 men; 86 grade II, 52 grade III, and 63 grade IV) who had preoperative diffusion tensor imaging for calculation of the ALPS index were retrospectively included. Information collected from each patient included sex, age, tumor grade, isocitrate dehydrogenase 1 (IDH1) mutation status, peritumoral brain edema volume, tumor volume, and ALPS index. Group differences in the ALPS index according to sex, tumor grade, and IDH1 mutation status were assessed using analysis of covariance with age adjustment. Linear regression analyses were performed to identify the factors associated with the ALPS index.ResultsGroup comparisons revealed that the ALPS index of grade II/III gliomas was significantly higher than that of grade IV gliomas (p < 0.001). The ALPS index of IDH1 mutant gliomas was significantly higher than that of IDH1 wild-type gliomas (p < 0.001). On multivariable linear regression analysis, IDH1 mutation (β = 0.308, p < 0.001) and peritumoral brain edema volume (β = −0.353, p < 0.001) were the two independent factors associated with the ALPS index.Conclusion IDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function.
Highlights
The glymphatic system has been recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain parenchymal interstitium [1]
We aimed to investigate the correlations of glymphatic function with the volumes of tumor and peritumoral brain edema, tumor grades, and isocitrate dehydrogenase 1 (IDH1) mutation status
On stepwise multivariable linear regression analysis, IDH1 mutation (b = 0.308; p < 0.001) and peritumoral brain edema volume (b = −0.353; p < 0.001) were the two independent factors associated with the along the perivascular space (ALPS) index
Summary
The glymphatic system has been recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain parenchymal interstitium [1]. In rodent studies, reduced CSF efflux rate [5] and remodeling of the glymphatic pathway [4] were observed in glioma-bearing mice, and these changes may be associated with the formation of peritumoral brain edema. Despite substantial knowledge having been gained from animal studies, further research is necessary to confirm whether the findings regarding the glymphatic system of animals apply to humans. Noninvasive approaches such as the morphological assessment of intracranial perivascular spaces with structural magnetic resonance imaging (MRI) [6,7,8,9] and measurement of water diffusivity using diffusion MRI [10,11,12] have been proposed for the evaluation of human glymphatic function
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