Combining weakly and strongly supervised learning improves strong supervision in Gleason pattern classification

Background: One challenge to train deep convolutional neural network (CNNs) models with whole slide images (WSIs) is providing the required large number of costly, manually annotated image regions. Strategies to alleviate the scarcity of annotated data include: using transfer learning, data augmentation and training the models with less expensive image-level annotations (weakly-supervised learning). However, it is not clear how to combine the use of transfer learning in a CNN model when different data sources are available for training or how to leverage from the combination of large amounts of weakly annotated images with a set of local region annotations. This paper aims to evaluate CNN training strategies based on transfer learning to leverage the combination of weak and strong annotations in heterogeneous data sources. The trade-off between classification performance and annotation effort is explored by evaluating a CNN that learns from strong labels (region annotations) and is later fine-tuned on a dataset with less expensive weak (image-level) labels. Results: As expected, the model performance on strongly annotated data steadily increases as the percentage of strong annotations that are used increases, reaching a performance comparable to pathologists (κ= 0.691 ± 0.02). Nevertheless, the performance sharply decreases when applied for the WSI classification scenario with κ= 0.307 ± 0.133. Moreover, it only provides a lower performance regardless of the number of annotations used. The model performance increases when fine-tuning the model for the task of Gleason scoring with the weak WSI labels κ= 0.528 ± 0.05. Conclusion: Combining weak and strong supervision improves strong supervision in classification of Gleason patterns using tissue microarrays (TMA) and WSI regions. Our results contribute very good strategies for training CNN models combining few annotated data and heterogeneous data sources. The performance increases in the controlled TMA scenario with the number of annotations used to train the model. Nevertheless, the performance is hindered when the trained TMA model is applied directly to the more challenging WSI classification problem. This demonstrates that a good pre-trained model for prostate cancer TMA image classification may lead to the best downstream model if fine-tuned on the WSI target dataset. We have made available the source code repository for reproducing the experiments in the paper: https://github.com/ilmaro8/Digital_Pathology_Transfer_Learning