A Novel Fully Automated MRI-Based Deep Learning Method For Classification Of 1p/19q Co-Deletion Status In Brain Gliomas

Abstract

BackgroundOne of the most important recent discoveries in brain glioma biology has been the identification of the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status as markers for therapy and prognosis. 1p/19q co-deletion is the defining genomic marker for oligodendrogliomas and confers a better prognosis and treatment response than gliomas without it. Our group has previously developed a highly accurate deep-learning network for determining IDH mutation status using T2-weighted MRI only. The purpose of this study was to develop a similar 1p/19q deep-learning classification network. MethodsMulti-parametric brain MRI and corresponding genomic information were obtained for 368 subjects from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). 1p/19 co-deletions were present in 130 subjects. 238 subjects were non co-deleted. A T2w image only network (1p/19q-net) was developed to perform 1p/19q co-deletion status classification and simultaneous single-label tumor segmentation using 3D-Dense-UNets. Threefold cross-validation was performed to generalize the network performance. ROC analysis was also performed. Dice-scores were computed to determine tumor segmentation accuracy. Results1p/19q-net demonstrated a mean cross validation accuracy of 93.46% across the 3 folds (93.4%, 94.35%, and 92.62%, standard dev=0.8) in predicting 1p/19q co-deletion status with a sensitivity and specificity of 0.90 {+/-}0.003 and 0.95 {+/-}0.01, respectively and a mean AUC of 0.95 {+/-}0.01. The whole tumor segmentation mean Dice-score was 0.80 {+/-} 0.007. ConclusionWe demonstrate high 1p/19q co-deletion classification accuracy using only T2-weighted MR images. This represents an important milestone toward using MRI to predict glioma histology, prognosis, and response to treatment. Keypoints1. 1p/19 co-deletion status is an important genetic marker for gliomas. 2. We developed a non-invasive, MRI based, highly accurate deep-learning method for the determination of 1p/19q co-deletion status that only utilizes T2 weighted MR images IMPORTANCE OF THE STUDYOne of the most important recent discoveries in brain glioma biology has been the identification of the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status as markers for therapy and prognosis. 1p/19q co-deletion is the defining genomic marker for oligodendrogliomas and confers a better prognosis and treatment response than gliomas without it. Currently, the only reliable way to determine 1p/19q mutation status requires analysis of glioma tissue obtained either via an invasive brain biopsy or following open surgical resection. The ability to non-invasively determine 1p/19q co-deletion status has significant implications in determining therapy and predicting prognosis. We developed a highly accurate, deep learning network that utilizes only T2-weighted MR images and outperforms previously published imagebased methods. The high classification accuracy of our T2w image only network (1p/19q-net) in predicting 1p/19q co-deletion status marks an important step towards image-based stratification of brain gliomas. Imminent clinical translation is feasible because T2-weighted MR imaging is widely available and routinely performed in the assessment of gliomas.