ToPoFM: Topology-Guided Pathology Foundation Model for High-Resolution Pathology Image Synthesis with Cellular-Level Control

Synthetic data generation emerges as a strategy to mitigate data scarcity in digital pathology, where complicated tissue and cellular features are correlated with cancer diagnosis. The synthesis of such visuals, however, suffers from limited inter class diversity and scarcity of cellular annotations. Current methodologies struggle with capturing the broad spectrum of pathology features, causing unpredictable objects and defected fidelity. Moreover, discrepancies in image resolution across developmental and operational phases can amplify the distribution shifts, undermining the precision of diagnosis. To address these challenges, we introduce TOpology guided PathOlogy Foundation Model (ToPoFM), a visual foundation model designed for the synthesis of high-resolution pathology images with cellular-level control. Our approach integrates a topology-informed cell arrangement generator to steer large language models for crafting synthetic cell arrangements. We correlate cell arrangement guidance with diffusion model for pathology content generation, then further implement a random sliding inference strategy, merging discrete low-resolution samplings into single high-resolution representation. Our model requires only small patches for training. The efficacy of ToPoFM is demonstrated through extensive experiments, complemented by expert validations, showing high fidelity on data synthesis. Additionally, we underscore the utility of our generated imagery as an augmentation tool, enhancing the performance of downstream tasks, including cancer subtype classification and segmentation.