Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multi-pool CEST MRI at 7.0 Tesla

Abstract

Background

Early identification of prognostic superior characteristics in glioma patients such as Isocitrate dehydrogenase(IDH)-mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promotor methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH-mutation status, MGMT promotor methylation, and differentiation of lower versus higher grade glioma (LGG vs. HGG) in newly-diagnosed patients employing relaxation-compensated multi-pool Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) at 7.0 Tesla (7T).

Methods

Thirty-one newly-diagnosed glioma patients were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser Effect (NOE) and isolated amide proton transfer (APT, downfield NOE-suppressed APT=dns-APT) CEST signals (mean value and 90^th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH-mutation, MGMT promotor methylation status, and differentiation of LGG vs. HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared to advanced MRI methods (apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) ROC/AUC analysis) obtained at 3T.

Results

dns-APT CEST contrasts yielded highest AUCs in IDH-mutation status prediction (dns-APT_mean=91.84%, p<0.01; dns-APT₉₀=97.96%, p<0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG vs. HGG (AUC: dns-APT_mean=0.78, p<0.05; dns-APT₉₀=0.83, p<0.05). There was no significant difference regarding MGMT promotor methylation status at any contrast (p>0.05).

Conclusions

Relaxation-compensated multi-pool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH-mutation status and differentiation of LGG vs. HGG and should therefore be considered as non-invasive MR biomarker in the diagnostic workup.