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

Research output: Contribution to journalArticle

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).

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalEuropean Radiology
DOIs
StateAccepted/In press - Dec 12 2017

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Methyltransferases
Glioblastoma
Amides
Methylation
Protons
DNA
DNA Methylation
Biomarkers
Area Under Curve

Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics. / Jiang, Shanshan; Rui, Qihong; Wang, Yu; Heo, Hye Young; Zou, Tianyu; Yu, Hao; Zhang, Yi; Wang, Xianlong; Du, Yongxing; Wen, Xinrui; Chen, Fangyao; Wang, Jihong; Eberhart, Charles G; Zhou, Jinyuan; Wen, Zhibo.

In: European Radiology, 12.12.2017, p. 1-9.

Research output: Contribution to journalArticle

Jiang, Shanshan ; Rui, Qihong ; Wang, Yu ; Heo, Hye Young ; Zou, Tianyu ; Yu, Hao ; Zhang, Yi ; Wang, Xianlong ; Du, Yongxing ; Wen, Xinrui ; Chen, Fangyao ; Wang, Jihong ; Eberhart, Charles G ; Zhou, Jinyuan ; Wen, Zhibo. / Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics. In: European Radiology. 2017 ; pp. 1-9.
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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).",
keywords = "Amide proton transfer-weighted imaging, Glioblastoma, Magnetic resonance imaging, Methylation, O6-methylguanine-DNA methyltransferase",
author = "Shanshan Jiang and Qihong Rui and Yu Wang and Heo, {Hye Young} and Tianyu Zou and Hao Yu and Yi Zhang and Xianlong Wang and Yongxing Du and Xinrui Wen and Fangyao Chen and Jihong Wang and Eberhart, {Charles G} and Jinyuan Zhou and Zhibo Wen",
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T1 - Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics

AU - Jiang, Shanshan

AU - Rui, Qihong

AU - Wang, Yu

AU - Heo, Hye Young

AU - Zou, Tianyu

AU - Yu, Hao

AU - Zhang, Yi

AU - Wang, Xianlong

AU - Du, Yongxing

AU - Wen, Xinrui

AU - Chen, Fangyao

AU - Wang, Jihong

AU - Eberhart, Charles G

AU - Zhou, Jinyuan

AU - Wen, Zhibo

PY - 2017/12/12

Y1 - 2017/12/12

N2 - 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).

AB - 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).

KW - Amide proton transfer-weighted imaging

KW - Glioblastoma

KW - Magnetic resonance imaging

KW - Methylation

KW - O6-methylguanine-DNA methyltransferase

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