Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma

  • Bio Joo
  • Kyunghwa Han
  • Sung Soo AhnEmail author
  • Yoon Seong Choi
  • Jong Hee Chang
  • Seok-Gu Kang
  • Se Hoon Kim
  • Jinyuan Zhou
  • Seung-Koo Lee
Magnetic Resonance



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.

Key Points

• 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.


Glioma Magnetic resonance imaging Isocitrate dehydrogenase Prognosis 



Amide proton transfer


Area under the curve


Concurrent chemoradiation therapy


High-grade glioma


Integrated area under the curve


Intraclass correlation coefficients


Isocitrate dehydrogenase


Karnofsky performance status


O6-methylguanine-DNA methyltransferase


Magnetic resonance imaging


Magnetization transfer ratio asymmetry


Overall survival


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.

Informed consent

The institutional review board waived the requirement to obtain informed patient consent for this retrospective study.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• diagnostic or prognostic study

• performed at one institution


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Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Bio Joo
    • 1
  • Kyunghwa Han
    • 1
  • Sung Soo Ahn
    • 1
    Email author
  • Yoon Seong Choi
    • 1
  • Jong Hee Chang
    • 2
  • Seok-Gu Kang
    • 2
  • Se Hoon Kim
    • 3
  • Jinyuan Zhou
    • 4
  • Seung-Koo Lee
    • 1
  1. 1.Department of Radiology and Research Institute of Radiological ScienceYonsei University College of MedicineSeoulSouth Korea
  2. 2.Department of NeurosurgeryYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department of PathologyYonsei University College of MedicineSeoulSouth Korea
  4. 4.Division of MRI Research, Department of RadiologyJohns Hopkins University School of MedicineBaltimoreUSA

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