Clinical Research Papers:

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

Sebastian Regnery, Sebastian Adeberg, Constantin Dreher, Johanna Oberhollenzer, Jan-Eric Meissner, Steffen Goerke, Johannes Windschuh, Katerina Deike-Hofmann, Sebastian Bickelhaupt, Moritz Zaiss, Alexander Radbruch, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Stefan Rieken, Jürgen Debus, Peter Bachert, Mark Ladd, Heinz-Peter Schlemmer and Daniel Paech _

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Oncotarget. 2018; 9:28772-28783. https://doi.org/10.18632/oncotarget.25594

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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

Correspondence to:

Daniel Paech, email: [email protected]

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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