Daniel Paech1, Johannes Windschuh2,3, Johanna Oberhollenzer1, Constantin Dreher1, Felix Sahm4,5, Jan-Eric Meissner2, Steffen Goerke2, Patrick Schuenke2, Moritz Zaiss6, Sebastian Regnery7, Sebastian Bickelhaupt1, Philipp Bäumer1,2, Martin Bendszus8, Wolfgang Wick9, Andreas Unterberg10, Peter Bachert, Mark Edward Ladd2,11, Heinz-Peter Schlemmer1, Alexander Radbruch1,12. 1. German Cancer Research Center, Division of Radiology, Heidelberg, Germany. 2. German Cancer Research Center, Division of Medical Physics in Radiology, Heidelberg, Germany. 3. Department of Radiology, New York University Langone Medical Center, New York, New York, USA. 4. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany. 5. CCU Neuropathology, German Consortium for Translational Cancer Research, German Cancer Research Center, Heidelberg, Germany. 6. Max-Planck-Institute for Biological Cybernetics, Magnetic Resonance Center, Tuebingen, Germany. 7. Department of Radiooncology, University Hospital Heidelberg, Heidelberg, Germany. 8. Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany. 9. Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany. 10. Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany. 11. Faculty of Physics and Astronomy and Faculty of Medicine, University of Heidelberg, Heidelberg, Germany. 12. Department of Radiology, University Hospital Essen, Essen, Germany.
Abstract
Background: Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla. Methods: Thirty-one patients with newly diagnosed glioma 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 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T. Results: dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05). Conclusions: Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.
Background: Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla. Methods: Thirty-one patients with newly diagnosed glioma 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 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T. Results: dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05). Conclusions: Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.
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