Multimodal synthesis of MRI and tabular data with diffusion in a joint latent space via cross-attention

Multimodal MRI provides complementary information for neuroimaging analysis, where different imaging modalities capture distinct anatomical, tissue, and pathological features that support the development and evaluation of downstream AI applications. Although large-scale structural MRI resources are increasingly available, their modality coverage is often uneven across public and pooled neuroimaging datasets. This uneven modality coverage is further complicated by heterogeneity across sites, scanners, and acquisition protocols, as well as demographic and clinical variables that are often sparse, inconsistently recorded, or unavailable across studies. Synthetic MRI generation can help address this imbalance by synthesizing target-modality volumes for dataset augmentation and controlled synthetic cohort creation. However, many existing MRI synthesis approaches are trained on narrow modality sets or relatively homogeneous cohorts, limiting their applicability to large pooled neuroimaging resources where modality availability, acquisition protocols, and metadata coverage vary substantially across datasets. Diffusion models have become an attractive approach for MRI synthesis because of their strong sample fidelity and diversity, but sampling directly in 3D voxel space is computationally expensive and slow at inference. Latent diffusion improves practicality by synthesizing MRI in a learned, 3D latent space, although generation quality depends on the autoencoder's reconstruction fidelity and the resulting latent distribution. Our approach combines a Wavelet-Fusion variational autoencoder (WF-VAE) latent compressor with a conditional 3D U-Net diffusion model trained in the learned latent space using explicit modality and metadata conditioning. Our proposed Wavelet-Fusion Diffusion Model (WFDM) achieved the strongest distributional alignment among the evaluated synthetic MRI generators.

Diffusion models have achieved remarkable quality in multi-modal MRI synthesis, but their computational cost (hundreds of sampling steps and separate models per modality) limits clinical deployment. We observe that this inefficiency stems from an unnecessary starting point: diffusion begins from pure noise, discarding the structural information already present in available MRI sequences. We propose WFM (Wavelet Flow Matching), which instead learns a direct flow from an informed prior, the mean of conditioning modalities in wavelet space, to the target distribution. Because the source and target share underlying anatomy and differ primarily in contrast, this formulation enables accurate synthesis in just 1-2 integration steps. A single 82M-parameter model with class conditioning synthesizes all four BraTS modalities (T1, T1c, T2, FLAIR), replacing four separate diffusion models totaling 326M parameters. On BraTS 2024, WFM achieves 26.8 dB PSNR and 0.94 SSIM, within 1-2 dB of diffusion baselines, while running 250-1000x faster (0.16-0.64s vs. 160s per volume). This speed-quality trade-off makes real-time MRI synthesis practical for clinical workflows. Code is available at https://github.com/yalcintur/WFM.

Controllable generative models of 3D medical images can synthesize volumes with specified clinical attributes, but this demands samples that are simultaneously high-fidelity, natively 3D, and faithful to the requested conditioning. We present CONFLUX, a latent diffusion model for chest computed tomography (CT): a 3D variational autoencoder compresses each volume, and a rectified-flow transformer generates in the latent space. Generation is conditioned on structured radiological metadata (18 abnormality findings, sex, age, and reconstruction kernel) through adaptive layer normalization. The model leads strong volumetric baselines on tri-planar Frechet distance (FID 32.3 vs. 74.6 for MAISI) while exposing direct control over clinical attributes. To strengthen that control we add an online reinforcement-learning post-training stage (group-relative policy optimization) that rewards how reliably a classifier recovers the requested findings from each generated volume. Judged by a separate, independent classifier, post-training removes 47% of the shortfall relative to real-scan reliability. We release the model and a ~200k synthetic chest-CT dataset with conditioning metadata spanning a wide variety of clinical findings.