Progressive Disease Image Generation with Ordinal-Aware Diffusion Models

Background/Objectives: Ulcerative Colitis (UC) lacks longitudinal visual data, which limits both disease progression modeling and the effectiveness of computer-aided diagnosis systems. These systems are further constrained by sparse intermediate disease stages and the discrete nature of the Mayo Endoscopic Score (MES). Meanwhile, synthetic image generation has made significant advances. In this paper, we propose novel ordinal embedding architectures for conditional diffusion models to generate realistic UC progression sequences from cross-sectional endoscopic images. Methods: By adapting Stable Diffusion v1.4 with two specialized ordinal embeddings (Basic Ordinal Embedder using linear interpolation and Additive Ordinal Embedder modeling cumulative pathological features), our framework converts discrete MES categories into continuous progression representations. Results: The Additive Ordinal Embedder outperforms alternatives, achieving superior distributional alignment (CMMD 0.4137, recall 0.6331) and disease consistency comparable to real data (Quadratic Weighted Kappa 0.8425, UMAP Silhouette Score 0.0571). The generated sequences exhibit smooth transitions between severity levels while maintaining anatomical fidelity. Conclusions: This work establishes a foundation for transforming static medical datasets into dynamic progression models and demonstrates that ordinal-aware embeddings can effectively capture disease severity relationships, enabling synthesis of underrepresented intermediate stages. These advances support applications in medical education, diagnosis, and synthetic data generation.