Ultra-high-field sodium MRI as biomarker for tumor extent, grade and IDH mutation status in glioma patients

Purpose: This prospective clinical trial investigated sodium (²³Na) MRI at 7 Tesla (T) field strength as biomarker for tumor extent, isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation in glioma patients.

Methods: 28 glioma patients underwent ²³Na MRI on a 7T scanner (Siemens Healthcare, Erlangen, Germany) parallel to standard 3T MRI before chemoradiation. Areas of Gadolinium-contrast enhancement (gdce), non-enhancing T2-hyperintensity (regarded as edema), necrosis, and normal-appearing white matter (nawm) were segmented on 3T MRI imaging and were co-registered with the ²³Na images. The median total ²³Na concentrations of all areas were compared by pairwise t-tests. Furthermore, areas of gdce and edema were merged to yield the whole tumor area without necrosis. Subsequently, the difference in median of the ²³Na concentration of this whole tumor area was compared between IDH-mutated and IDH wild-type gliomas as well as MGMT methylated and MGMT not-methylated glioblastomas using Whitney-Mann U-tests. All p-values were corrected after the Bonferroni-Holm procedure.

Results: The ²³Na concentration increased successively from nawm to necrotic areas (mean ± sd: nawm = 37.84 ± 5.87 mM, edema = 54.69 ± 10.64 mM, gdce = 61.72 ± 12.95 mM, necrosis = 81.88 ± 17.53 mM) and the concentrations differed statistically significantly between all regarded areas (adjusted p-values for all pairwise comparisons < 0.05). Furthermore, IDH-mutated gliomas showed significantly higher ²³Na concentrations than IDH wild-type gliomas (median [interquartile range]: IDH wild-type = 52.37 mM [45.98 - 58.56 mM], IDH mutated = 65.02 mM [58.87-67.05 mM], p = 0.039). Among the glioblastomas, there was a trend towards increased ²³Na concentration in MGMT methylated tumors that did not reach statistical significance (median [interquartile range]: MGMT methylated = 57.59 mM [50.70 - 59.17 mM], MGMT not methylated = 48.78 mM [45.88 - 53.91 mM], p = 1.0).

Conclusions: ²³Na MRI correlates with the IDH mutation status and could therefore enhance image guidance towards biopsy sites as wells as image-guided surgery and radiotherapy. Furthermore, the successive decrease of ²³Na concentration from central necrosis to normal-appearing white matter suggests a correlation with tumor infiltration.

Keywords: Glioblastoma; Glioma; IDH mutation; Non-invasive biomarker; Sodium imaging; Ultra-high-field MRI.