OrgaCast: A Trustworthy Spatiotemporal Diffusion Model for Fluorescence Organoid Forecasting

Accurately forecasting the spatiotemporal dynamics of biological systems, such as human pluripotent stem cell (hPSC)-derived cardiac organoids, from microscopy time-series is a critical challenge in biomedicine with profound implications for drug discovery. Existing generative models often fail to capture the intricate dynamics of organoid development, struggling with their irregular morphology, indistinct boundaries, and complex spatiotemporal patterns. To overcome these limitations, we introduce OrgaCast, a novel multimodal conditional diffusion model for high-fidelity organoid forecasting. OrgaCast uniquely conditions the generative process on three synergistic modalities: (i) historical image sequences, captured by a dedicated spatiotemporal control module; (ii) structured numerical metadata defining experimental conditions; and (iii) descriptive text captions summarizing the biological context. This comprehensive conditioning enables the generation of forecasts with high visual accuracy and biological plausibility. Furthermore, to enhance the model's utility in critical research settings, we introduce a post-hoc uncertainty quantification method that produces intuitive confidence maps, bolstering the interpretability and trustworthiness of predictions. Extensive experiments on a challenging cardiac organoid dataset demonstrate that OrgaCast outperforms baselines in metrics such as SSIM, PSNR, and LPIPS. Our framework presents a robust solution for biological forecasting, promising to accelerate research discovery while minimizing experimental costs and manual effort.