European Radiology

, Volume 28, Issue 5, pp 2115–2123 | Cite as

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

  • Shanshan Jiang
  • Qihong Rui
  • Yu Wang
  • Hye-Young Heo
  • Tianyu Zou
  • Hao Yu
  • Yi Zhang
  • Xianlong Wang
  • Yongxing Du
  • Xinrui Wen
  • Fangyao Chen
  • Jihong Wang
  • Charles G. Eberhart
  • Jinyuan Zhou
  • Zhibo Wen
Molecular Imaging
  • 332 Downloads

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).

Keywords

Glioblastoma O6-methylguanine-DNA methyltransferase Magnetic resonance imaging Amide proton transfer-weighted imaging Methylation 

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

Notes

Acknowledgements

The authors thank Ms. Mary McAllister for editorial assistance.

Compliance with ethical standards

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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Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  1. 1.Department of Radiology, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Division of MR Research, Department of RadiologyJohns Hopkins UniversityBaltimoreUSA
  3. 3.Department of RadiologyFutian Traditional Chinese Medicine HospitalShenzhenChina
  4. 4.Department of Pathology, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  5. 5.Department of Neurology, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  6. 6.Department of Epidemiology and Health Statistics, School of Public HealthXi’an Jiaotong University Health Science CenterXi’anChina
  7. 7.Department of Radiation Physics, Division of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  8. 8.Department of PathologyJohns Hopkins UniversityBaltimoreUSA

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