Glioma grading, molecular feature classification, and microstructural characterization using MR diffusional variance decomposition (DIVIDE) imaging.

Abstract

To evaluate the potential of diffusional variance decomposition (DIVIDE) for grading, molecular feature classification, and microstructural characterization of gliomas. Participants with suspected gliomas underwent DIVIDE imaging, yielding parameter maps of fractional anisotropy (FA), mean diffusivity (MD), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), total mean kurtosis (MKT), MKA/MKT, and microscopic fractional anisotropy (μFA). Tumor type and grade, isocitrate dehydrogenase (IDH) 1/2 mutant status, and the Ki-67 labeling index (Ki-67 LI) were determined after surgery. Statistical analysis included 33 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG). Tumor diffusion metrics were compared between HGG and LGG, among grades, and between wild and mutated IDH types using appropriate tests according to normality assessment results. Receiver operating characteristic and Spearman correlation analysis were also used for statistical evaluations. FA, MD, MKA, MKI, MKT, μFA, and MKA/MKT differed between HGG and LGG (FA: p = 0.047; MD: p = 0.037, others p < 0.001), and among glioma grade II, III, and IV (FA: p = 0.048; MD: p = 0.038, others p < 0.001). All diffusion metrics differed between wild-type and mutated IDH tumors (MKI: p = 0.003; others: p < 0.001). The metrics that best discriminated between HGG and LGGs and between wild-type and mutated IDH tumors were MKT and FA respectively (area under the curve 0.866 and 0.881). All diffusion metrics except FA showed significant correlation with Ki-67 LI, and MKI had the highest correlation coefficient (rs = 0.618). DIVIDE is a promising technique for glioma characterization and diagnosis. • DIVIDE metrics MKI is related to cell density heterogeneity while MKA and μFA are related to cell eccentricity. • DIVIDE metrics can effectively differentiate LGG from HGG and IDH mutation from wild-type tumor, and showed significant correlation with the Ki-67 labeling index. • MKI was larger than MKA which indicates predominant cell density heterogeneity in gliomas. • MKA and MKI increased with grade or degree of malignancy, however with a relatively larger increase in the cell eccentricity metric MKA in relation to the cell density heterogeneity metric MKI.