TumorFlow: Physics-Guided Longitudinal MRI Synthesis of Glioblastoma Growth

Precise prognostic modeling of glioblastoma (GBM) under varying treatment interventions is essential for optimizing clinical outcomes. While generative AI has shown promise in simulating GBM evolution, existing methods typically treat interventions as static conditional inputs rather than dynamic decision variables. Consequently, they fail to capture the complex, reciprocal interplay between tumor evolution and treatment response. To bridge this gap, we present Brain-WM, a pioneering brain GBM world model that unifies next-step treatment prediction and future MRI generation, thereby capturing the co-evolutionary dynamics between tumor and treatment. Specifically, Brain-WM encodes spatiotemporal dynamics into a shared latent space for joint autoregressive treatment prediction and flow-based future MRI generation. Then, instead of a conventional monolithic framework, Brain-WM adopts a novel Y-shaped Mixture-of-Transformers (MoT) architecture. This design structurally disentangles heterogeneous objectives, successfully leveraging cross-task synergies while preventing feature collapse. Finally, a synergistic multi-timepoint mask alignment objective explicitly anchors latent representations to anatomically grounded tumor structures and progression-aware semantics. Extensive validation on internal and external multi-institutional cohorts demonstrates the superiority of Brain-WM, achieving 91.5% accuracy in treatment planning and SSIMs of 0.8524, 0.8581, and 0.8404 for FLAIR, T1CE, and T2W sequences, respectively. Ultimately, Brain-WM offers a robust clinical sandbox for optimizing patient healthcare. The source code is made available at https://github.com/thibault-wch/Brain-GBM-world-model.

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

Complete and high-quality multi-modal Magnetic Resonance Imaging (MRI) is essential for accurate neuro-oncological assessment, as each contrast provides complementary anatomical and pathological information. However, acquiring all modalities (e.g., T1c, T1n, T2w, T2f) for every patient is often impractical due to prolonged scan times, cost, and patient discomfort, potentially limiting comprehensive tumour evaluation. We propose 3D-MC-SAGAN (3D Multi-Contrast Self-Attention Generative Adversarial Network), a unified 3D multi-contrast synthesis framework that generates high-fidelity missing modalities from a single T2w input while explicitly preserving tumour characteristics. The model employs a multi-scale 3D encoder--decoder generator with residual connections and a novel Memory-Bounded Hybrid Attention (MBHA) block to capture long-range dependencies efficiently, and is trained with a WGAN-GP critic and an auxiliary domain classification head to produce T2f, T1n, and T1c volumes within a unified network. To ensure anatomical and pathological fidelity, we incorporate a frozen 3D U-Net-based segmentation network that enforces a tumour-consistency constraint during training. A composite objective combining adversarial, reconstruction, perceptual, structural similarity, contrast-classification, and segmentation-guided losses further promotes both global realism and tumour-preserving structure. Extensive experiments on 3D brain MRI datasets demonstrate that 3D-MC-SAGAN achieves state-of-the-art quantitative performance and produces visually coherent, anatomically plausible contrasts with improved distributional realism. Importantly, the proposed method maintains tumour segmentation accuracy comparable to that achieved using fully acquired multi-modal inputs, highlighting its potential to reduce acquisition burden while preserving clinically meaningful information.