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Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics

  • Molecular Imaging
  • Published:
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Abstract

Objectives

To explore the feasibility of using amide proton transfer-weighted (APTw) MRI metrics as surrogate biomarkers to identify the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in glioblastoma (GBM).

Methods

Eighteen newly diagnosed GBM patients, who were previously scanned at 3T and had a confirmed MGMT methylation status, were retrospectively analysed. For each case, a histogram analysis in the tumour mass was performed to evaluate several quantitative APTw MRI metrics. The Mann-Whitney test was used to evaluate the difference in APTw parameters between MGMT methylated and unmethylated GBMs, and the receiver-operator-characteristic analysis was further used to assess diagnostic performance.

Results

Ten GBMs were found to harbour a methylated MGMT promoter, and eight GBMs were unmethylated. The mean, variance, 50th percentile, 90th percentile and Width10-90 APTw values were significantly higher in the MGMT unmethylated GBMs than in the MGMT methylated GBMs, with areas under the receiver-operator-characteristic curves of 0.825, 0.837, 0.850, 0856 and 0.763, respectively, for the discrimination of MGMT promoter methylation status.

Conclusions

APTw signal metrics have the potential to serve as valuable imaging biomarkers for identifying MGMT methylation status in the GBM population.

Key Points

• APTw-MRI is applied to predict MGMT promoter methylation status in GBMs.

• GBMs with unmethylated MGMT promoter present higher APTw-MRI than methylated GBMs.

• Multiple APTw histogram metrics can identify MGMT methylation status.

• Mean APTw values showed the highest diagnostic accuracy (AUC = 0.825).

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Abbreviations

ADC:

Apparent diffusion coefficient

APTw:

Amide proton transfer-weighted

AUC:

Area under the curve

CEST:

Chemical exchange-dependent saturation transfer

FLAIR:

Fluid-attenuated inversion recovery

GBM:

Glioblastoma

Gd-T1w:

Gadolinium-enhanced T1-weighted

MGMT:

O6-methylguanine-DNA methyltransferase

MRI:

Magnetic resonance imaging

ROC:

Receiver operator characteristic curve

T1w:

T1-weighted

T2w:

T2-weighted

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Acknowledgements

The authors thank Ms. Mary McAllister for editorial assistance.

Funding

This study was partially supported by grants from National Natural Science Foundation of China (81171322), Guangdong Provincial Natural Science Foundation (2014A030313271, S2012010009114), Guangdong Provincial Science and Technology Project (2014A020212726), Southern Medical University clinical research project (LC2016ZD028), and the National Institutes of Health (R01EB009731, R01CA166171).

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Authors and Affiliations

  1. Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China

    Shanshan Jiang, Qihong Rui, Tianyu Zou, Hao Yu, Xianlong Wang, Yongxing Du & Zhibo Wen

  2. Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, MD, 21287, USA

    Shanshan Jiang, Hye-Young Heo, Yi Zhang & Jinyuan Zhou

  3. Department of Radiology, Futian Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China

    Shanshan Jiang

  4. Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Yu Wang

  5. Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Xinrui Wen

  6. Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China

    Fangyao Chen

  7. Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jihong Wang

  8. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA

    Charles G. Eberhart

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  1. Shanshan Jiang
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  2. Qihong Rui
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  3. Yu Wang
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  4. Hye-Young Heo
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  5. Tianyu Zou
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  6. Hao Yu
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  7. Yi Zhang
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  8. Xianlong Wang
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  9. Yongxing Du
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  10. Xinrui Wen
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  11. Fangyao Chen
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  12. Jihong Wang
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  13. Charles G. Eberhart
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  14. Jinyuan Zhou
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  15. Zhibo Wen
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Corresponding authors

Correspondence to Shanshan Jiang or Zhibo Wen.

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Guarantor

The scientific guarantor of this publication is Zhibo Wen, MD, PhD.

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 (Dr. Fangyao Chen) has significant statistical expertise.

No complex statistical methods were necessary for this paper.

Ethical approval

Institutional Review Board approval was obtained.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Study subjects or cohorts overlap

Three study subjects have been previously reported in one of our previous papers, in which we evaluated the diagnostic values of APTw imaging in differentiate PCNSL and malignant gliomas, see Ref. [29].

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

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Jiang, S., Rui, Q., Wang, Y. et al. Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics. Eur Radiol 28, 2115–2123 (2018). https://doi.org/10.1007/s00330-017-5182-4

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