SAFE-Diff: Scale-Aware Attention and Feature-Dispersive Diffusion with Uncertainty Estimation for Contrast-Enhanced Breast MRI Synthesis

Inferring contrast enhancement from one pre-contrast breast MRI slice is underdetermined: post-contrast appearance contains physiological information that is not uniquely encoded in baseline anatomy. Optimizing only paired pixel fidelity can suppress uncertain lesion enhancement, whereas adversarial or stochastic generative objectives can favor realistic post-contrast appearance without guaranteeing patient-specific lesion fidelity. We introduce MIRAGE, a residual 2D U-Net that combines global reconstruction and perceptual losses with three forms of lesion-aware supervision available only during training: an asymmetric penalty for missed tumor enhancement, multi-scale auxiliary tumor segmentation, and guidance through a frozen post-contrast tumor segmentation nnU-Net. We evaluate the method on 301 cases from the multi-centre MAMA-SYNTH data using eight complementary image-, region-, radiomics-, and segmentation-based metrics. MIRAGE ranks first on six metrics and markedly improves downstream lesion localization over tuned pix2pix, conditional diffusion, and latent bridge-matching baselines. The generative alternatives retain advantages in LPIPS or contrast classification, revealing a clear fidelity-utility trade-off. Leave-one-in and leave-one-out ablations show that the losses are partly redundant for lesion localization but exert distinct effects on appearance, radiomics, and boundary accuracy. These results support task-aware synthesis while also showing that its apparent optimality is conditional on the downstream models and metrics used to define utility.

Multi-contrast brain MRI provide complementary soft-tissue characteristics that aid in the screening and diagnosis of diseases. However, limited scanning time, image corruption and various imaging protocols often result in incomplete multi-contrast images. While current approaches excel in image synthesis, they often struggle to synthesize critical tumor regions and exploit contextual information in multi-contrast brain MRI effectively. To address this issue, we propose a synthesis-centric, segmentation-assisted closed-loop framework with retrieval augmentation synthesis. Our method overall takes a generative adversarial architecture, which aims to synthesize missing contrasts from any combination of available ones with a single model. To explicitly capture tumor semantics and focus synthesis on tumor regions, we add an auxiliary segmentation branch that predicts tumor masks and feeds them back as semantic conditioning in synthesis branch, thereby learning tumor-aware representations in the model and improving synthesis fidelity. Furthermore, we propose a dual-bank retrieval augmentation strategy. It dynamically queries two external knowledge bases, namely a tumor masks memory bank for crucial tumor context and cross-image contrast feature memory bank for global style information, to augment synthesis. Verified on two public multi-contrast magnetic resonance brain datasets: BraTs2020 and UCSF-BMSR, the proposed method is effective in handling medical brain images synthesis tasks and shows superior performance compared to previous methods. Code is available at:https://github.com/iBizzard/SSCF.git

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is essential for breast cancer management, but reliance on gadolinium-based contrast agents (GBCAs) restricts use in contraindicated populations, prolongs scan protocols, and presents environmental toxicity concerns. Contrast synthesis offers a non-invasive alternative; however, existing approaches struggle to balance spatial realism with temporal continuity, suffer from slow iterative sampling, underutilize structural priors, and lack clinical validation. We propose a novel conditioned latent transport framework that predicts contrast enhancement in a single forward pass. By anchoring the latent trajectory to the pre-contrast anatomy and applying continuous time conditioning, the model synthesizes patient-specific contrast evolution at any acquisition time. The proposed approach outperforms baseline and the state-of-the-art models across spatial, perceptual, temporal, and distributional metrics. Evaluated on an independent external cohort, the method demonstrates robustness to domain shifts induced by scanner noise as well as differing acquisition protocol. Furthermore, our synthetic contrast enhancement significantly improved downstream tumor segmentation performance, yielding a 22.4% relative increase in Dice coefficient (0.60 vs. 0.49 baseline pre-contrast, p < 0.01), reducing boundary segmentation error by over 39%, while outperforming all other generative model baselines. Finally, a reader study involving four breast radiologists evaluated the image quality, kinetic fidelity, and diagnostic viability of our synthesized sequences across 40 randomly selected cases. The results demonstrated that in 70% of cases, synthesized images provided sufficient clinical information to support the same management decisions as real DCE-MRI, suggesting a path toward safer and faster contrast-free or contrast-reduced imaging workflows.