MRI-Based Deep-Learning Method for Determining Glioma MGMT Promoter Methylation Status

AJNR Am J Neuroradiol. 2021 May;42(5):845-852. doi: 10.3174/ajnr.A7029. Epub 2021 Mar 4.

Abstract

Background and purpose: O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation confers an improved prognosis and treatment response in gliomas. We developed a deep learning network for determining MGMT promoter methylation status using T2 weighted Images (T2WI) only.

Materials and methods: Brain MR imaging and corresponding genomic information were obtained for 247 subjects from The Cancer Imaging Archive and The Cancer Genome Atlas. One hundred sixty-three subjects had a methylated MGMT promoter. A T2WI-only network (MGMT-net) was developed to determine MGMT promoter methylation status and simultaneous single-label tumor segmentation. The network was trained using 3D-dense-UNets. Three-fold cross-validation was performed to generalize the performance of the networks. Dice scores were computed to determine tumor-segmentation accuracy.

Results: The MGMT-net demonstrated a mean cross-validation accuracy of 94.73% across the 3 folds (95.12%, 93.98%, and 95.12%, [SD, 0.66%]) in predicting MGMT methylation status with a sensitivity and specificity of 96.31% [SD, 0.04%] and 91.66% [SD, 2.06%], respectively, and a mean area under the curve of 0.93 [SD, 0.01]. The whole tumor-segmentation mean Dice score was 0.82 [SD, 0.008].

Conclusions: We demonstrate high classification accuracy in predicting MGMT promoter methylation status using only T2WI. Our network surpasses the sensitivity, specificity, and accuracy of histologic and molecular methods. This result represents an important milestone toward using MR imaging to predict prognosis and treatment response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / genetics*
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Deep Learning*
  • Glioma / diagnostic imaging*
  • Glioma / genetics*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neural Networks, Computer
  • Promoter Regions, Genetic
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tumor Suppressor Proteins / genetics*

Substances

  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes