Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients

// Sebastian Regnery 1, 2 , Sebastian Adeberg 3 , Constantin Dreher 2 , Johanna Oberhollenzer 2 , Jan-Eric Meissner 4 , Steffen Goerke 4 , Johannes Windschuh 4 , Katerina Deike-Hofmann 2 , Sebastian Bickelhaupt 2 , Moritz Zaiss 5 , Alexander Radbruch 2 , Martin Bendszus 6 , Wolfgang Wick 7 , Andreas Unterberg 8 , Stefan Rieken 1 , Jurgen Debus 1 , Peter Bachert 4 , Mark Ladd 4, 9, 10 , Heinz-Peter Schlemmer 2 and Daniel Paech 2 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany 2 German Cancer Research Center (DKFZ), Division of Radiology, Heidelberg, Germany 3 German Cancer Research Center (DKFZ), HIRO (Heidelberg Institute for Radiation Oncology), Heidelberg, Germany 4 German Cancer Research Center (DKFZ), Division of Medical Physics in Radiology, Heidelberg, Germany 5 Max-Planck-Institute, Tubingen, Germany 6 Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany 7 Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany 8 Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany 9 Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany 10 Faculty of Medicine, University of Heidelberg, Heidelberg, Germany Correspondence to: Daniel Paech, email: d.paech@dkfz.de Keywords: magnetic resonance imaging; amide-proton-transfer-imaging; nuclear overhauser imaging; glioblastoma; predictive biomarker Received: March 29, 2018      Accepted: May 24, 2018      Published: June 19, 2018 ABSTRACT Purpose: To prospectively investigate chemical exchange saturation transfer (CEST) MRI in glioblastoma patients as predictor of early tumor progression after first-line treatment. Experimental Design: Twenty previously untreated glioblastoma patients underwent CEST MRI employing a 7T whole-body scanner. Nuclear Overhauser effect (NOE) as well as amide proton transfer (APT) CEST signals were isolated using Lorentzian difference (LD) analysis and relaxation compensated by the apparent exchange-dependent relaxation rate (AREX) evaluation. Additionally, NOE-weighted asymmetric magnetic transfer ratio (MTRasym) and downfield-NOE-suppressed APT (dns-APT) were calculated. Patient response to consecutive treatment was determined according to the RANO criteria. Mean signal intensities of each contrast in the whole tumor area were compared between early-progressive and stable disease. Results: Pre-treatment tumor signal intensity differed significantly regarding responsiveness to first-line therapy in NOE-LD ( p = 0.0001), NOE-weighted MTRasym ( p = 0.0186) and dns-APT ( p = 0.0328) contrasts. Hence, significant prediction of early progression was possible employing NOE-LD (AUC = 0.98, p = 0.0005), NOE-weighted MTRasym (AUC = 0.83, p = 0.0166) and dns-APT (AUC = 0.80, p = 0.0318). The NOE-LD provided the highest sensitivity (91%) and specificity (100%). Conclusions: CEST derived contrasts, particularly NOE-weighted imaging and dns-APT, yielded significant predictors of early progression after fist-line therapy in glioblastoma. Therefore, CEST MRI might be considered as non-invasive tool for customization of treatment in the future.