Annotation-free glioma grading from pathological images using ensemble deep learning

Glioma grading is critical for treatment selection, and the fine classification between glioma grades II and III is still a pathological challenge. Traditional systems based on a single deep learning (DL) model can only show relatively low accuracy in distinguishing glioma grades II and III. Introducing ensemble DL models by combining DL and ensemble learning techniques, we achieved annotation-free glioma grading (grade II or III) from pathological images. We estab-lished multiple tile-level DL models using residual network ResNet-18 architecture and then used DL models as component classifiers to develop ensemble DL models to achieve patient-level glioma grading. Whole-slide images of 507 subjects with low-grade glioma (LGG) from the Cancer Genome Atlas (TCGA) were included. The 30 DL models exhibited an average area under the curve (AUC) of 0.7991 in patient-level glioma grading. Single DL models showed large variation, and the median between-model cosine similarity was 0.9524, significantly smaller than the threshold of 1.0. The ensemble model based on logistic regression (LR) methods with a 14-component DL classifier (LR-14) demonstrated a mean patient-level accuracy and AUC of 0.8011 and 0.8945, respectively. Our proposed LR-14 ensemble DL model achieved state-of-the-art performance in glioma grade II and III classifications based on unannotated pathological images.