Brain-WM: Brain Glioblastoma World Model

Glioblastoma exhibits diverse, infiltrative, and patient-specific growth patterns that are only partially visible on routine MRI, making it difficult to reliably assess true tumor extent and personalize treatment planning and follow-up. We present a biophysically-conditioned generative framework that synthesizes biologically realistic 3D brain MRI volumes from estimated, spatially continuous tumor-concentration fields. Our approach combines a generative model with tumor-infiltration maps that can be propagated through time using a biophysical growth model, enabling fine-grained control over tumor shape and growth while preserving patient anatomy. This enables us to synthesize consistent tumor growth trajectories directly in the space of real patients, providing interpretable, controllable estimation of tumor infiltration and progression beyond what is explicitly observed in imaging. We evaluate the framework on longitudinal glioblastoma cases and demonstrate that it can generate temporally coherent sequences with realistic changes in tumor appearance and surrounding tissue response. These results suggest that integrating mechanistic tumor growth priors with modern generative modeling can provide a practical tool for patient-specific progression visualization and for generating controlled synthetic data to support downstream neuro-oncology workflows. In longitudinal extrapolation, we achieve a consistent 75% Dice overlap with the biophysical model while maintaining a constant PSNR of 25 in the surrounding tissue. Our code is available at: https://github.com/valentin-biller/lgm.git

Clinical decision-making in oncology requires predicting dynamic disease evolution, a task current static AI predictors cannot perform. While world models (WMs) offer a paradigm for generative prediction, existing medical applications remain limited. Existing methods often rely on stochastic diffusion models, focusing on visual reconstruction rather than causal, physiological transitions. Furthermore, in medical domain, models like MeWM typically ignore patient-specific temporal and clinical contexts and lack a feedback mechanism to link predictions to treatment decisions. To address these gaps, we introduce CLARITY, a medical world model that forecasts disease evolution directly within a structured latent space. It explicitly integrates time intervals (temporal context) and patient-specific data (clinical context) to model treatment-conditioned progression as a smooth, interpretable trajectory, and thus generate physiologically faithful, individualized treatment plans. Finally, CLARITY introduces a novel prediction-to-decision framework, translating latent rollouts into transparent, actionable recommendations. CLARITY demonstrates state-of-the-art performance in treatment planning. On the MU-Glioma-Post dataset, our approach outperforms recent MeWM by 12%, and significantly surpasses all other medical-specific large language models.

Brain tumors result in 20 years of lost life on average. Standard therapies induce complex structural changes in the brain that are monitored through MRI. Recent developments in artificial intelligence (AI) enable conditional multimodal image generation from clinical data. In this study, we investigate AI-driven generation of follow-up MRI in patients with intracranial tumors through conditional image generation. This approach enables realistic modeling of post-radiotherapy changes, allowing for treatment optimization. The public SAILOR dataset of 25 patients was used to create a 2D rectified flow model conditioned on axial slices of pre-treatment MRI and RT dose maps. Cross-attention conditioning was used to incorporate temporal and chemotherapy data. The resulting images were validated with structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), Dice scores and Jacobian determinants. The resulting model generates realistic follow-up MRI for any time point, while integrating treatment information. Comparing real versus predicted images, SSIM is 0.88, and PSNR is 22.82. Tissue segmentations from real versus predicted MRI result in a mean Dice-Sørensen coefficient (DSC) of 0.91. The rectified flow (RF) model enables up to 250x faster inference than Denoising Diffusion Probabilistic Models (DDPM). The proposed model generates realistic follow-up MRI in real-time, preserving both semantic and visual fidelity as confirmed by image quality metrics and tissue segmentations. Conditional generation allows counterfactual simulations by varying treatment parameters, producing predicted morphological changes. This capability has potential to support adaptive treatment dose planning and personalized outcome prediction for patients with intracranial tumors. Code will be available upon peer-reviewed publication at: https://github.com/SelenaIHuisman/RF-GlioPREDICT