Distilling knowledge from graph neural networks trained on cell graphs to non-neural student models.

The development and refinement of artificial intelligence (AI) and machine learning algorithms have been an area of intense research in radiology and pathology, particularly for automated or computer-aided diagnosis. Whole Slide Imaging (WSI) has emerged as a promising tool for developing and utilizing such algorithms in diagnostic and experimental pathology. However, patch-wise analysis of WSIs often falls short of capturing the intricate cell-level interactions within local microenvironment. A robust alternative to address this limitation involves leveraging cell graph representations, thereby enabling a more detailed analysis of local cell interactions. These cell graphs encapsulate the local spatial arrangement of cells in histopathology images, a factor proven to have significant prognostic value. Graph Neural Networks (GNNs) can effectively utilize these spatial feature representations and other features, demonstrating promising performance across classification tasks of varying complexities. It is also feasible to distill the knowledge acquired by deep neural networks to smaller student models through knowledge distillation (KD), achieving goals such as model compression and performance enhancement. Traditional approaches for constructing cell graphs generally rely on edge thresholds defined by sparsity/density or the assumption that nearby cells interact. However, such methods may fail to capture biologically meaningful interactions. Additionally, existing works in knowledge distillation primarily focus on distilling knowledge between neural networks. We designed cell graphs with biologically informed edge thresholds or criteria to address these limitations, moving beyond density/sparsity-based definitions. Furthermore, we demonstrated that student models do not need to be neural networks. Even non-neural models can learn from a neural network teacher. We evaluated our approach across varying dataset complexities, including the presence or absence of distribution shifts, varying degrees of imbalance, and different levels of graph complexity for training GNNs. We also investigated whether softened probabilities obtained from calibrated logits offered better guidance than raw logits. Our experiments revealed that the teacher's guidance was effective when distribution shifts existed in the data. The teacher model demonstrated decent performance due to its higher complexity and ability to use cell graph structures and features. Its logits provided rich information and regularization to students, mitigating the risk of overfitting the training distribution. We also examined the differences in feature importance between student models trained with the teacher's logits and their counterparts trained on hard labels. In particular, the student model demonstrated a stronger emphasis on morphological features in the Tuberculosis (TB) dataset than the models trained with hard labels. This emphasis aligns closely with the features that pathologists typically prioritize for diagnostic purposes. Future work could explore designing alternative teacher models, evaluating the proposed approach on larger datasets, and investigating causal knowledge distillation as a potential extension.