Noninvasive assessment of glymphatic dysfunction and IDH mutation in glioma with DTI-ALPS and DTI metrics

The occurrence and development of glioma are closely related to neuro-immunity. The glymphatic system (GS), a brain waste-clearance pathway, plays a critical role in neuro-immunity. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a non-invasive method to assess glymphatic dysfunction. This study had the following aims: (I) to quantify glioma-induced glymphatic dysfunction using DTI-ALPS, and (II) to explore the role of ALPS-index and DTI metrics in evaluating isocitrate dehydrogenase (IDH) mutation and the predictive value of survival in glioma patients.

A total of 146 gliomas and 61 healthy controls (HC) were included in the study. The ALPS-index and DTI metrics were all included in the calculation. Comparisons were made between the ALPS-index in both cerebral hemispheres, and between patients and controls, as well as the ALPS-index and DTI metrics [fractional anisotropy (FA) mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)] among different tumor grades. Additionally, the ALPS-index in different tumor locations (frontal/temporal/parietal/occipital/basal) was initially investigated. The diagnostic performance of each metric for IDH mutation was assessed by receiver operating characteristic (ROC) analysis, and the predictive value of each metric for survival was evaluated through the Cox proportional risk model.

In low-grade gliomas (Grades II-III), the ALPS-index of ipsilateral gliomas was significantly lower than that of contralateral gliomas (Grade II: 1.31±0.18 vs. 1.43±0.21; P=0.01; Grade III: 1.30±0.22 vs. 1.40±0.21; P=0.03); in high-grade gliomas, the opposite situation was observed (Grade IV: 1.34±0.19 vs. 1.24±0.16; P=0.01). The same results were found when comparing tumor location, survival, and IDH mutations between the two brain hemispheres. The bilateral ALPS-index in patients were significantly decreased compared with those in HC (P<0.01). We found no statistical difference in tumor locations regarding ALPS-index and other tensor metrics (FA/MD/AD/RD, all P>0.05). For grade II gliomas, combining the ALPS-index with AD, RD, or MD substantially improved IDH mutation diagnostic accuracy [area under the curve (AUC): 0.88-0.89 vs. 0.72-0.81 for single metrics]. However, this predictive utility declined in grade III-IV gliomas (AUC <0.80); Cox analysis identified clinical factors (tumor grade, sex, age, IDH mutations) and DTI metrics [MD: hazard ratio (HR) =2.48, 95% confidence interval (CI): 1.35-4.58, P<0.01; AD: HR =2.73, 95% CI: 1.46-5.09, P<0.01; RD: HR =2.49, 95% CI: 1.33-4.65, P<0.01] as significant predictors of overall survival (OS).

The ALPS-index can indirectly reflect the impairment of the GS. The combined model of the ALPS-index and DTI metrics is significant for predicting IDH mutation in low-grade gliomas. The ALPS-index and another non-invasive imaging biomarker can reflect the characteristics of glioma more comprehensively. However, the GS impairment of gliomas in different tumor locations still requires further study.