Cellflow: Advancing pathological image augmentation from spatial views to temporal trajectories

Deep learning has advanced pathological image analysis but remains constrained by limited annotated data, especially for fine-grained diagnostic tasks such as tumor subtyping, grading, and cellularity assessment. While data augmentation alleviates this issue, existing methods are restricted to spatial manipulations that lack morphological plausibility and overlook the temporal attributes of pathological state transition. To address this gap, we propose Cellflow, the first temporal-aware generative framework for pathological image augmentation. Cellflow models pathological transition as smooth trajectories on a biological image manifold, generating intermediate states via a stair-based diffusion bridge with classifier-guided probability-flow ordinary differential equations. This design produces morphologically plausible sequences that capture both cellular details and tissue-level architecture. Evaluated on 7 diverse datasets across organs, staining modalities, and diagnostic tasks, Cellflow consistently outperforms 6 spatial augmentation methods and 4 state-of-the-art generative models, yielding improved classification performance, higher image fidelity, and preservation of temporal coherence. Quantitative cellularity analysis provides additional validation of the biological authenticity of transition sequences. By introducing temporal modeling into pathological data augmentation, Cellflow establishes a paradigm shift from spatial manipulations to biologically grounded temporal trajectories that advances robust model training, rare disease exploration, and educational simulation in computational pathology. The Code is available at https://github.com/Rowerliu/Cellflow.