Diffusion along the perivascular space as a potential biomarker for glioma grading and isocitrate dehydrogenase 1 mutation status prediction

Background: The diffusion tensor image analysis along the perivascular space (DTI-ALPS) may have the potential to reflect glymphatic dysfunction in patients with glioma. The study aimed to determine the correlation of DTI-ALPS with glioma grade and isocitrate dehydrogenase 1 (IDH1) genotype and to then compare the ALPS index with other diffusion metrics.Methods: In this study, 81 patients with glioma and 31 healthy controls underwent magnetic resonance imaging (MRI) examination. The ALPS-index, fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) were calculated. Comparisons were made between the left and right hemispheres and between patients and controls. IDH1 status was compared after age adjustment. The diagnostic performance of each metric was assessed via receiver operating characteristic (ROC) analysis.Results: : In patients with glioma, the ALPS-index of the hemisphere ipsilateral to glioma was significantly lower than that of the hemisphere contralateral to glioma (1.417 +/- 0.177 vs. 1.478 +/- 0.165; P=0.002), and the bilateral ALPS-index values in patients were significantly decreased compared with those in healthy controls. The ALPS-index was significantly higher in lower-grade gliomas (LrGGs) than that in glioblastomas (GBMs) (1.495 +/- 0.151 vs. 1.320 +/- 0.159; P<0.001) and was significantly lower in IDH1-wild-type LrGGs than in IDH1-mutant LrGGs (1.400 +/- 0.185 vs. 1.530 +/- 0.123; P=0.036). FA, MD, and MK also showed significant differences between LrGGs and GBMs and between IDH1-mutant and IDH1-wild-type LrGGs (P<0.05). Furthermore, the combination of the ALPS-index with FA, MD, or MK, exhibited superior discrimination ability compared to each metric used alone. The ALPS-index combined with MD had the highest area under the curve (AUC) of 0.854 as compared to that of 0.614-0.807 for a single metric in glioma grading, while for IDH1 mutation prediction, this combination had the highest AUC of 0.861 as compared to that of 0.707- 0.778 for a single metric.Conclusions: The reduced ALPS-index may reflect tumor-induced glymphatic system impairment, and the ALPS-index may be able to complement conventional diffusion metrics in glioma grading and IDH1 genotyping.