Deep Generative Classification of Blood Cell Morphology

Simon Deltadahl, Julian D. Gilbey, Christine van Laer, Nancy Boeckx, Mathie Leers, Tanya Freeman, Laura Aiken, Timothy Farren, Matthew Smith, Mohamad Zeina, BloodCounts Consortium, Concetta Piazzese, Joseph Taylor, Nicholas S. Gleadall, Carola-Bibiane Schönlieb, Suthesh Sivapalaratnam, Michael Roberts, Parashkev Nachev

Abstract: Accurate classification of haematological cells is critical for diagnosing blood disorders, but presents significant challenges for machine automation owing to the complexity of cell morphology, heterogeneities of biological, pathological, and imaging characteristics, and the imbalance of cell type frequencies. We introduce CytoDiffusion, a diffusion-based classifier that effectively models blood cell morphology, combining accurate classification with robust anomaly detection, resistance to distributional shifts, interpretability, data efficiency, and superhuman uncertainty quantification. Our approach outperforms state-of-the-art discriminative models in anomaly detection (AUC 0.976 vs. 0.919), resistance to domain shifts (85.85% vs. 74.38% balanced accuracy), and performance in low-data regimes (95.88% vs. 94.95% balanced accuracy). Notably, our model generates synthetic blood cell images that are nearly indistinguishable from real images, as demonstrated by a Turing test in which expert haematologists achieved only 52.3% accuracy (95% CI: [50.5%, 54.2%]). Furthermore, we enhance model explainability through the generation of directly interpretable counterfactual heatmaps. Our comprehensive evaluation framework, encompassing these multiple performance dimensions, establishes a new benchmark for medical image analysis in haematology, ultimately enabling improved diagnostic accuracy in clinical settings. Our code is available at https://github.com/Deltadahl/CytoDiffusion.