Negative Instance Guided Self-Distillation Framework for Whole Slide Image Analysis.

Histopathology image classification is an important clinical task, and current deep learning-based whole-slide image (WSI) classification methods typically cut WSIs into small patches and cast the problem as multi-instance learning. The mainstream approach is to train a bag-level classifier, but their performance on both slide classification and positive patch localization is limited because the instance-level information is not fully explored. In this article, we propose a negative instance-guided, self-distillation framework to directly train an instance-level classifier end-to-end. Instead of depending only on the self-supervised training of the teacher and the student classifiers in a typical self-distillation framework, we input the true negative instances into the student classifier to guide the classifier to better distinguish positive and negative instances. In addition, we propose a prediction bank to constrain the distribution of pseudo instance labels generated by the teacher classifier to prevent the self-distillation from falling into the degeneration of classifying all instances as negative. We conduct extensive experiments and analysis on three publicly available pathological datasets: CAMELYON16, PANDA, and TCGA, as well as an in-house pathological dataset for cervical cancer lymph node metastasis prediction. The results show that our method outperforms existing methods by a large margin. Code will be publicly available.