Posterior Samplings are Missing Modalities Generators for Medical Image Translation

Medical image-to-image (I2I) translation enables virtual scanning, i.e. the synthesis of a target imaging modality from a source one without additional acquisitions. Despite growing interest, most proposed methods operate on 2D slices, are evaluated on isolated tasks with different experimental set-ups and lack clinical validation. The primary contribution of this work is a reproducible, standardized comparative evaluation of 3D I2I translation methods in oncological imaging, designed to standardize preprocessing, splitting, inference, and multi-level evaluation across heterogeneous clinical tasks. Within this framework, we compare seven generative models, three Generative Adversarial Networks (GANs: Pix2Pix, CycleGAN, SRGAN) and four latent generative models (Latent Diffusion Model, Latent Diffusion Model+ControlNet, Brownian Bridge, Flow Matching), across eleven datasets spanning three anatomical regions (head/neck, lung, pelvis) and four translation directions (cone-beam CT to CT, MRI to CT, CT to PET, MRI T2-weighted to T2-FLAIR), for a total of 77 experiments under uniform training, inference, and evaluation conditions. The results show that GANs outperform latent generative models across all tasks, with SRGAN achieving statistically significant superiority. Our lesion-level analysis reveals that all models struggle with small lesions and that, in CT to PET synthesis, models reproduce lesion shape more reliably than absolute uptake-related intensity. We also performed a Visual Turing test administered to 17 physicians, including 15 radiologists, which shows near-chance classification accuracy (56.7%), confirming that synthetic volumes are largely indistinguishable from real acquisitions, while exposing a dissociation between quantitative metrics and clinical preference.

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.

AI-driven image-to-image synthesis is rapidly advancing, with growing applications in medical imaging. Multi-modal image analysis plays a crucial role in optimizing examination quality, yet acquiring multiple imaging modalities in clinical settings remains resource-intensive and time-consuming, especially for 3D imaging. To address this challenge, we propose a novel image-to-image translation model based on Brownian Bridge Diffusion Models (BBDM), which synthesizes magnetic resonance imaging (MRI) sequences from 2D axial slices. Our approach integrates a variational encoder-guided diffusion mechanism, leveraging probabilistic image distributions to enhance synthesis quality. Evaluated on the BraTS 2021 dataset, our Probabilistic-BBDM (Prob-BBDM) achieves superior performance across multiple translation tasks, reaching up to 88.46% SSIM and 26.09 dB PSNR, with consistent improvements over baselines. Notably, our diffusion process requires only 4 steps, making it computationally efficient while maintaining high-quality synthesis. To further validate generalizability, we test Prob-BBDM on an external third-party dataset, demonstrating consistent performance across domains. Additionally, we assess the clinical utility of the synthesized slices by using them as input to a pre-trained segmentation model. Tumor segmentation yields a Dice score of 88.71% and an HD95 of 3.49 mm, confirming that the synthesized slices preserve critical diagnostic information. These results highlight the potential of Prob-BBDM for high-quality, efficient, and generalizable MRI synthesis, offering a promising step toward improved medical image translation.