StaX-Net: Stackelberg Interleaved Asymmetric Network for Cross-Modality Medical Image Translation

Cross-modality medical image translation can reduce the burden of multi-modal acquisitions, yet the field remains constrained by two coupled limitations: methods operate on 2D slices or 3D patches rather than whole volumes, and train a separate model for each translation task. Both stem from a single cause, the absence of a sufficiently strong volumetric prior, which forces generative models to learn anatomical appearance and cross-modality mapping simultaneously, an ill-posed problem at the scale of available paired datasets. We propose to decouple these objectives. A large-scale pretrained 3D variational autoencoder provides a compact latent representation of volumetric appearance, reducing translation to a conditional flow-matching problem. This compression makes whole-volume processing tractable, while a resolution-aware sampling strategy preserves native anatomical scale. We train a single model jointly across inter-modality (MRI$\to$CT, CBCT$\to$CT) and intra-modality (MRI$\to$MRI) tasks over three multi-center datasets. Across all tasks, whole-volume processing outperforms its patch-based counterpart, and the multi-task model matches task-specific baselines while replacing $N$ networks with one. Crucially, joint training unlocks capabilities inaccessible to task-specific approaches: zero-shot generalization to anatomical regions unseen during training, within 0.15 SSIM of the fully supervised model, and compositional cross-dataset translation along paths never directly supervised. These results suggest that combining a strong volumetric prior with multitask training is a scalable route toward synthesis systems that generalize beyond their training distribution. Code is available at https://github.com/arco-group/Whole-Volume-Latent-FM.

Strongly paired medical image translation contains a substantial component that can be predicted directly from the source. The current reality is that pure deterministic prediction can smooth away fine detail, while generative models can recover detail but may also introduce unnecessary or potentially harmful variation. We propose PredRA, a fast framework that uses the deterministic prediction as a stable reference and further extracts additional deterministic components from the residual during generative refinement, thereby improving fidelity while maintaining perceptual quality. The goal is simple: we view the entire residual-based generative process as an optimization problem and derive a practical solution that recovers useful residual detail through controlled refinement while keeping the prediction close to the paired target. Mechanism studies further show that useful residual information follows structured patterns, but its usefulness is difficult to estimate reliably at the voxel level. We therefore globally control how much of the residual refinement is added to the deterministic prediction, thereby reducing the accumulation of unnecessary uncertainty. PredRA therefore combines deterministic component extraction with controlled stochastic refinement for fast, fidelity-preserving, and perceptually strong medical image translation. We validate the approach across multiple real-world datasets, showing that controlled refinement improves fidelity to the paired target compared with full residual refinement while retaining much of the perceptual benefit of generative modeling. PredRA achieves competitive or superior performance to substantially larger state-of-the-art models with 1.4-11.9x fewer total parameters and 3.1-26.2x fewer trainable parameters, while its 32-step flow sampler requires 31.25x fewer sampling steps than the matched 1000-step DDPM.

Magnetic resonance imaging comes in various modality contrasts that provide complementary anatomical and pathological information. Complete multimodal acquisitions are often unavailable due to time and protocol constraints. This leads to real-world datasets with missing modalities, where conventional medical image translation methods are typically limited to fixed source-target settings or require retraining for each observed source-target pair. We propose a unified framework that formulates missing-modality generation as a linear inverse problem under a joint distribution and solves it via posterior sampling with a flow matching model. By learning a joint prior over the complete modality set, our method can reconstruct arbitrary missing modalities at inference time by guiding the sampling trajectory to enforce measurement consistency with observed modalities. We further mitigate inter-modality error propagation in multi-target generation by adopting a many-to-one sampling strategy. Experiments on BraTS and IXI datasets show that our method achieves the best performance over baselines across most missing-modality scenarios. In downstream tumor segmentation, synthesized images from our method result in higher segmentation performance, indicating better preservation of clinically relevant structures.