Automated Grading of Gliomas using Deep Learning in Digital Pathology Images: A modular approach with ensemble of convolutional neural networks

Brain glioma is the most common primary malignant brain tumors in adults with different pathologic subtypes: Lower Grade Glioma (LGG) Grade II, Lower Grade Glioma (LGG) Grade III, and Glioblastoma Multiforme (GBM) Grade IV. The survival and treatment options are highly dependent of this glioma grade. We propose a deep learning-based, modular classification pipeline for automated grading of gliomas using digital pathology images. Whole tissue digitized images of pathology slides obtained from The Cancer Genome Atlas (TCGA) were used to train our deep learning modules. Our modular pipeline provides diagnostic quality statistics, such as precision, sensitivity and specificity, of the individual deep learning modules, and (1) facilitates training given the limited data in this domain, (2) enables exploration of different deep learning structures for each module, (3) leads to developing less complex modules that are simpler to analyze, and (4) provides flexibility, permitting use of single modules within the framework or use of other modeling or machine learning applications, such as probabilistic graphical models or support vector machines. Our modular approach helps us meet the requirements of minimum accuracy levels that are demanded by the context of different decision points within a multi-class classification scheme. Convolutional Neural Networks are trained for each module for each sub-task with more than 90% classification accuracies on validation data set, and achieved classification accuracy of 96% for the task of GBM vs LGG classification, 71% for further identifying the grade of LGG into Grade II or Grade III on independent data set coming from new patients from the multi-institutional repository.