Diffusion-Based Synthesis of Complete 3D Biparametric Prostate MRI

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.

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.

Missing data problems, such as missing modalities in multi-modal brain MRI and missing slices in cardiac MRI, pose significant challenges in clinical practice. Existing methods rely on external guidance to supply detailed missing-state information for instructing generative models to synthesize missing MRIs. However, manual indicators are not always available or reliable in real-world scenarios due to the unpredictable nature of clinical environments. Moreover, these explicit masks are not informative enough to provide guidance for improving semantic consistency. In this work, we argue that generative models should infer and recognize missing states in a self-perceptive manner, enabling them to better capture subtle anatomical and pathological variations. Towards this goal, we propose CoPeDiT, a shared completeness-perception framework for 3D MRI synthesis, following a common conditioning strategy with task-specific instantiations for different missing-data scenarios. Specifically, we incorporate dedicated pretext tasks into our tokenizer, CoPeVAE, empowering it to learn completeness-aware discriminative prompt tokens, and design MDiT3D, a specialized diffusion transformer architecture for 3D MRI synthesis that effectively uses the completeness-aware prompt tokens as guidance to enhance semantic consistency in 3D space. Comprehensive evaluations on three large-scale MRI datasets demonstrate that CoPeDiT consistently improves upon state-of-the-art methods across diverse missing patterns, yielding high-fidelity and structurally consistent MRI synthesis. Our code is available at https://github.com/JK-Liu7/CoPeDiT.