Now You Have My Healthy Attention: A U-DiT for Brain-MRI Inpainting

Medical image inpainting has the potential to improve automated brain MRI analysis by reconstructing healthy tissue within pathological regions. We introduce RARF, a task-agnostic region-aware rectified flow framework for masked data generation. We instantiate the framework for 3D brain MRI inpainting as our submission to the BraTS Inpainting Challenge 2026. RARF restricts the stochastic interpolation process to the inpainting region, while the observed voxels remain fixed and provide patient-specific anatomical context. A three-dimensional neural network receives the partially voided image, with Gaussian noise filling the missing region, together with the inpainting mask and the corresponding timestep. The model is trained using masked flow-matching and reconstruction-consistency objectives, combined with mask-aware preprocessing and data augmentation. During inference, the learned velocity field transports the initial noise toward a plausible reconstruction of the missing tissue, which is then combined with the unchanged observed anatomy. Experiments under the BraTS evaluation protocol show that the proposed approach produces competitive reconstructions while maintaining anatomical consistency. Source code is available at: https://github.com/TomasGuija/rarf.

Brain-MRI inpainting replaces a masked region of a scan with synthesized, anatomically plausible healthy tissue, so that analysis tools built for healthy brains can be applied to images they would otherwise reject. On the BraTS local-synthesis benchmark, which ranks submissions on the structural similarity index (SSIM), the peak signal-to-noise ratio, and the mean squared error (MSE) jointly, the strongest recent models are accurate, but several report blurry synthesized regions and attribute this to the mean-seeking behavior of the $\ell_1$ and MSE terms in their training losses. We address this in post-processing, forming a deep ensemble of the two co-first-place 2025 models and training a lightweight residual refiner on the ensemble's own outputs under an $\ell_1$ loss augmented with a structural-similarity term whose weight $λ$ we vary. At a moderate $λ$ the refiner improves SSIM over the ensemble, from $0.8767$ to $0.8780$ on a held-out reproduction of the official scorer and from $0.8555$ to $0.8572$ on the official validation leaderboard, with essentially no change in MSE. The gain is small but consistent, improving $62.6\%$ of the held-out cases with a signed-rank $p=2.2\times10^{-7}$, whereas over-weighting the structural term reverses it. Two ablations bound the effect. Adding any third model to the two-model ensemble degrades it, and classical unsharp masking fails to improve SSIM at any strength (best $0.8765$ against $0.8767$), so the gain reflects learned rather than indiscriminate sharpening. The result is a cheap, reproducible post-processing stage that improves an already strong ensemble without any large-scale retraining.

Brain tumors induce complex structural deformations that obscure the patient' s original neuroanatomy, making it difficult to distinguish tumor-induced changes from inherent anatomical variability. Reconstructing a subject-specific pseudo-healthy brain can provide a critical reference for such analysis, but this task is inherently counterfactual, as paired pre-tumor scans and explicit healthy guidance are unavailable. We propose BrainNormalizer, a diffusion-based framework for subject-specific pseudo-healthy brain MRI reconstruction that enables anatomy-informed reconstruction without requiring paired data or explicit healthy references. The framework learns anatomical priors and edge-based structural conditioning through a two-stage training strategy consisting of inpainting-based diffusion fine-tuning and ControlNet-based edge conditioning. At inference, counterfactual pseudo-healthy reconstruction is achieved through a deliberate misalignment strategy, where tumorous inputs are paired with non-tumorous prompts and mirrored contralateral edge maps. This allows subject-specific anatomical guidance to be constructed from the patient's own anatomy, enabling anatomically consistent pseudo-healthy reconstruction that preserves individual structural characteristics. Experiments on the BraTS2020 dataset demonstrate that BrainNormalizer achieves improved distributional realism, symmetry-based structural consistency, and reduced false positive detection compared to existing methods. These results indicate that the proposed framework provides a principled approach for subject-specific counterfactual reconstruction and supports downstream analysis of tumor-induced deformation.