PreMix: Boosting Multiple Instance Learning in Digital Histopathology through Pre-training with Intra-Batch Slide Mixing

The classification of gigapixel-sized whole slide images (WSIs), digital representations of histological slides obtained via a high-resolution scanner, faces significant challenges associated with the meticulous and time-consuming nature of fine-grained labeling. While weakly-supervised multiple instance learning (MIL) has emerged as a promising approach, current MIL methods are constrained by their limited ability to leverage the wealth of information embedded within unlabeled WSIs. This limitation often necessitates training MIL feature aggregators from scratch after the feature extraction process, hindering efficiency and accuracy. PreMix extends the general MIL framework by pre-training the MIL aggregator with an intra-batch slide mixing approach. Specifically, PreMix incorporates Barlow Twins Slide Mixing during pre-training, enhancing its ability to handle diverse WSI sizes and maximizing the utility of unlabeled WSIs. Combined with Mixup and Manifold Mixup during fine-tuning, PreMix achieves a mean of 4.7% performance improvement over the baseline MIL framework, the hierarchical image pyramid transformer (HIPT), on the Camelyon16 dataset. The observed improvement across a range of active learning acquisition functions and WSI-labeled training budgets highlights the framework's adaptability to diverse datasets and varying resource constraints. Ultimately, PreMix paves the way for more efficient and accurate WSI classification under limited WSI-labeled datasets, encouraging the broader adoption of unlabeled WSI data in histopathological research. The code is available at https://anonymous.4open.science/r/PreMix