Clinical Research Papers:
Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients
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Sebastian Regnery1,2, Sebastian Adeberg3, Constantin Dreher2, Johanna Oberhollenzer2, Jan-Eric Meissner4, Steffen Goerke4, Johannes Windschuh4, Katerina Deike-Hofmann2, Sebastian Bickelhaupt2, Moritz Zaiss5, Alexander Radbruch2, Martin Bendszus6, Wolfgang Wick7, Andreas Unterberg8, Stefan Rieken1, Jürgen Debus1, Peter Bachert4, Mark Ladd4,9,10, Heinz-Peter Schlemmer2 and Daniel Paech2
1Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany
2German Cancer Research Center (DKFZ), Division of Radiology, Heidelberg, Germany
3German Cancer Research Center (DKFZ), HIRO (Heidelberg Institute for Radiation Oncology), Heidelberg, Germany
4German Cancer Research Center (DKFZ), Division of Medical Physics in Radiology, Heidelberg, Germany
5Max-Planck-Institute, Tübingen, Germany
6Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
7Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany
8Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany
9Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany
10Faculty of Medicine, University of Heidelberg, Heidelberg, Germany
Daniel Paech, email: firstname.lastname@example.org
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
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.
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