Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma
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To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV).
We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test.
High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62–6.34) and PFS (HR = 2.22, 95% CI = 1.33–3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208).
High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status.
• Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma.
• APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma.
• APT imaging may be valuable for preoperative screening and treatment guidance.
KeywordsGlioma Magnetic resonance imaging Isocitrate dehydrogenase Prognosis
Amide proton transfer
Area under the curve
Concurrent chemoradiation therapy
Integrated area under the curve
Intraclass correlation coefficients
Karnofsky performance status
Magnetic resonance imaging
Magnetization transfer ratio asymmetry
Polymerase chain reaction
Progression free survival
Region of interests
The authors thank Ha-Kyu Jeong (Korea Basic Science Institute, Chungcheongbuk-do, Korea) for his help with protocol optimization and for the valuable suggestions.
This research received funding from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2014R1A1A1002716, 2017R1D1A1B03030440) and National Institutes of Health (P41 EB015909, R01 CA166171, R01 EB009731).
Compliance with ethical standards
The scientific guarantor of this publication is Professor Seung-Koo Lee, MD, PhD, from Yonsei University College of Medicine.
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
One of the authors has significant statistical expertise.
Kyunghwa Han, PhD
Department of Radiology and Research Institute of Radiological Science, College of Medicine, Yonsei University College of Medicine, Seoul, Korea.
The institutional review board waived the requirement to obtain informed patient consent for this retrospective study.
Institutional Review Board approval was obtained.
• diagnostic or prognostic study
• performed at one institution
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