HemExp: Clinically-Guided Latent Diffusion for Modeling Hematoma Expansion

Computational models of blood clotting improve understanding of thrombus formation, but their clinical application remains limited because many model inputs are difficult to measure and patient-specific data are often sparse. We present a computational framework based on latent neural differential equations that infers unknown model parameters from sparse measurements and forecasts thrombosis progression. We demonstrate the framework using data generated from a multiphysics blood-clotting model in which clot growth is governed by the coagulation cascade and diffusion. Four known biochemical inputs (fibrinogen and factors IX, VIII, and V), together with sparse early clot-size observations, are used to infer the tissue-factor parameter and predict subsequent clot growth. We compare seven probabilistic methods: stochastic neural ordinary differential equations (SNODE), stochastic neural functional differential equations (SNFDE), a latent neural-process baseline, a monotone probabilistic deep ensemble, empirical trajectory retrieval, PCA-ridge Gaussian posterior, and Gompertz-curve retrieval. SNODE achieved the best performance in inferring the unknown input and forecasting future clot-growth trajectories. SNFDE performed similarly and consistently outperformed the other non-differential models. Prediction accuracy improved as more observations became available, whereas longer forecasting horizons increased uncertainty and decreased accuracy. Latent neural differential equations thus effectively combine parameter inference and clot-growth forecasting from sparse measurements, providing a promising foundation for personalized thrombosis modeling.

Forecasting anatomical changes such as tumor growth and neurodegeneration is a challenging generative vision task. Morphological evolution is subtle relative to static anatomy, highly patient-specific, and inherently stochastic. Existing methods struggle with several issues: deterministic networks ignore biological stochasticity, while standard diffusion models require computationally prohibitive multi-pass sampling to quantify uncertainty. We propose MUMINS (Metadata-conditioned Uncertainty-aware Medical Image Next-state Synthesis), an efficient diffusion framework that jointly diffuses a baseline scan and its follow-up residual, summed to synthesize the follow-up scan, while concurrently predicting a spatial uncertainty map, in a single reverse diffusion process. Conditioned on the time interval and relevant metadata, it preserves fine-grained anatomy by dynamically re-injecting the baseline as a soft anchor at every denoising step, and a negative-log-likelihood head learns the uncertainty map to explicitly flag error-prone regions. Designed without organ-specific heuristics, the same architecture is reused across anatomies via separate, dataset-specific retraining. Extensive evaluations demonstrate that dataset-specific retraining of MUMINS matches or outperforms dedicated, domain-specific state-of-the-art methods on lung CT (PNG) and brain MRI (OASIS-3). Project page: https://github.com/aolivtous/MUMINS.

Accurately modeling longitudinal brain MRI progression is crucial for understanding neurodegenerative diseases and predicting individualized structural changes. Existing state-of-the-art approaches, such as Brain Latent Progression (BrLP), often use multi-stage training pipelines with auxiliary conditioning modules but suffer from architectural complexity, suboptimal use of conditional clinical covariates, and limited guarantees of anatomical consistency. We propose Anatomically Guided Latent Diffusion Model (AG-LDM), a segmentation-guided framework that enforces anatomically consistent progression while substantially simplifying the training pipeline. AG-LDM conditions latent diffusion by directly fusing baseline anatomy, noisy follow-up states, and clinical covariates at the input level, a strategy that avoids auxiliary control networks by learning a unified, end-to-end model that represents both anatomy and progression. A lightweight 3D tissue segmentation model (WarpSeg) provides explicit anatomical supervision during both autoencoder fine-tuning and diffusion model training, ensuring consistent brain tissue boundaries and morphometric fidelity. Experiments on 31,713 ADNI longitudinal pairs and zero-shot evaluation on OASIS-3 demonstrate that AG-LDM matches or surpasses more complex diffusion models, achieving highly competitive image quality and 15-20% reduction in volumetric errors in generated images. AG-LDM also exhibits markedly stronger utilization of temporal and clinical covariates (3.5-31.5x higher covariate sensitivity than BrLP) and generates biologically plausible counterfactual trajectories, accurately capturing hallmarks of Alzheimer's progression such as limbic atrophy and ventricular expansion. These results highlight AG-LDM as an efficient, anatomically grounded framework for reliable brain MRI progression modeling.