Relaxation-compensated amide proton transfer (APT) MRI signal intensity is associated with survival and progression in high-grade glioma patients
The purpose of this study was to investigate the association of relaxation-compensated chemical exchange saturation transfer (CEST) MRI with overall survival (OS) and progression-free survival (PFS) in newly diagnosed high-grade glioma (HGG) patients.
Twenty-six patients with newly diagnosed high-grade glioma (WHO grades III–IV) were included in this prospective IRB-approved study. CEST MRI was performed on a 7.0-T whole-body scanner. Association of patient OS/PFS with relaxation-compensated CEST MRI (amide proton transfer (APT), relayed nuclear Overhauser effect (rNOE)/NOE, downfield-rNOE-suppressed APT (dns-APT)) and diffusion-weighted imaging (apparent diffusion coefficient) were assessed using the univariate Cox proportional hazards regression model. Hazard ratios (HRs) and corresponding 95% confidence intervals were calculated. Furthermore, OS/PFS association with clinical parameters (age, gender, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status, and therapy: biopsy + radio-chemotherapy vs. debulking surgery + radio-chemotherapy) were tested accordingly.
Relaxation-compensated APT MRI was significantly correlated with patient OS (HR = 3.15, p = 0.02) and PFS (HR = 1.83, p = 0.009). The strongest association with PFS was found for the dns-APT metric (HR = 2.61, p = 0.002). These results still stand for the relaxation-compensated APT contrasts in a homogenous subcohort of n = 22 glioblastoma patients with isocitrate dehydrogenase (IDH) wild-type status. Among the tested clinical parameters, patient age (HR = 1.1, p = 0.001) and therapy (HR = 3.68, p = 0.026) were significant for OS; age additionally for PFS (HR = 1.04, p = 0.048).
Relaxation-compensated APT MRI signal intensity is associated with overall survival and progression-free survival in newly diagnosed, previously untreated glioma patients and may, therefore, help to customize treatment and response monitoring in the future.
• Amide proton transfer (APT) MRI signal intensity is associated with overall survival and progression in glioma patients.
• Relaxation compensation enhances the information value of APT MRI in tumors.
• Chemical exchange saturation transfer (CEST) MRI may serve as a non-invasive biomarker to predict prognosis and customize treatment.
KeywordsMagnetic resonance imaging Glioma Glioblastoma Survival Biomarkers, cancer
Amide proton transfer
APT contrast calculated with the AREX metric
APT contrast calculated with the LD metric
Apparent exchange-dependent relaxation
Chemical exchange saturation transfer
Downfield relayed nuclear Overhauser effect suppressed APT
Fluid-attenuated inversion recovery
Field of view
Gadolinium-based contrast agents
T1-weighted gadolinium contrast-enhanced MRI
Karnofsky performance scale
Medical Imaging Interaction Toolkit
Magnetization-prepared rapid gradient echo
Magnetization transfer ratio asymmetry
Magnetization transfer Lorentzian difference
Nuclear Overhauser effect
NOE contrast calculated with the AREX metric
NOE contrast calculated with the LD metric
Response assessment in neuro-oncology
Relative cerebral blood volume
Relayed nuclear Overhauser effect
Turbo spin echo
Simultaneous mapping of water shift and B1
World Health Organization
The authors would like to thank Prof. Dr. Annette Kopp-Schneider for her invaluable help with the statistical analyses and Joseph Weygand, M.S., for carefully proof reading and reviewing of the manuscript.
The authors state that this work has not received any funding.
Compliance with ethical standards
The scientific guarantor of this publication is Dr. Daniel Paech.
Conflict of interest
The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.
Statistics and biometry
Prof. Dr. Annette Kopp-Schneider (Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany) kindly provided statistical advice for this manuscript.
Written informed consent was obtained from all subjects (patients) in this study.
Institutional Review Board approval was obtained.
Study subjects or cohorts overlap
The study cohort has previously been reported (Paech et al. Neuro Oncol, 2018, noy073 and Regnery et al. Oncotarget, 2018, 9:28772–28783) and a subcohort of eleven patients has been included in methodical publications (Zaiss et al. Neuroimage, 2015, 112:180–188 and Zaiss et al. MRM, 2017, 77(1):196–208). However, no investigations of overall survival and progression-free survival have previously been performed.
• diagnostic or prognostic
• performed at one institution
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