RARF: Region-Aware Rectified Flows for 3D Brain MRI Inpainting

The ASNR-MICCAI BraTS Local Synthesis (Inpainting) task asks for the anatomically plausible completion of healthy brain tissue within a masked region of a T1-weighted MRI, providing a tumor-free anatomical reference for downstream analysis. As the task is scored by distortion metrics (SSIM, PSNR, MSE), we build a deterministic regression model and focus on giving it inductive biases tailored to inpainting. Our network follows the U-DiT principle of performing self-attention on a downsampled token grid: a volumetric encoder-decoder imports long-range context through a downsampled global self-attention block with three-dimensional rotary position embeddings, while convolutions and skip connections preserve high-frequency detail. Two ideas drive our results. First, we constrain the attention so that occluded ("void") tokens attend only to known-healthy tokens of the same volume, with a learned bias toward each query's contralateral homologue, forcing the completion to be inferred from observed anatomy rather than from other unknown regions. Second, we add a contralateral-symmetry input that supplies the mirrored healthy hemisphere as a patient-specific prior; since the brain is approximately bilaterally symmetric and lesions are typically unilateral, this prior improves the distortion metrics at matched structural similarity. On the official BraTS-2026 validation leaderboard our submission reaches a mean healthy-region SSIM of $0.864$, PSNR of $24.7$,dB and MSE of $4.6{\times}10^{-3}$ over $219$ cases. We further analyse the residual smoothness inherent to distortion-optimal regression and discuss its implications for anatomical realism.

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.

Accurate longitudinal analysis of brain MRI is often hindered by evolving lesions, which bias automated neuroimaging pipelines. While deep generative models have shown promise in inpainting these lesions, most existing methods operate cross-sectionally or lack 3D anatomical continuity. We present a novel pseudo-3D longitudinal inpainting framework based on Denoising Diffusion Probabilistic Models (DDPM). Our approach utilizes multi-channel conditioning to incorporate longitudinal context from distinct visits (t_1, t_2) and extends Region-Aware Diffusion (RAD) to the medical domain, focusing the generative process on pathological regions without altering surrounding healthy tissue. We evaluated our model against state-of-the-art baselines on longitudinal brain MRI from 93 patients. Our model significantly outperforms the leading baseline (FastSurfer-LIT) in terms of perceptual fidelity, reducing the Learned Perceptual Image Patch Similarity (LPIPS) distance from 0.07 to 0.03 while effectively eliminating inter-slice discontinuities. Furthermore, our model demonstrates high longitudinal stability with a Temporal Fidelity Index of 1.024, closely approaching the ideal value of 1.0 and substantially narrowing the gap compared to LIT's TFI of 1.22. Notably, the RAD mechanism provides a substantial gain in efficiency; our framework achieves an average processing time of 2.53 min per volume, representing approximately 10x speedup over the 24.30 min required by LIT. By leveraging longitudinal priors and region-specific denoising, our framework provides a highly reliable and efficient preprocessing step for the study of progressive neurodegenerative diseases. A derivative dataset consisting of 93 pre-processed scans used for testing will be available upon request after acceptance. Code will be released upon acceptance.