Towards Personalized Multi-Modal MRI Synthesis across Heterogeneous Datasets

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.

Accurate synthesis of computed tomography (CT) images from magnetic resonance imaging (MRI) is clinically valuable for cranial applications such as attenuation correction, radiotherapy planning, and image-guided interventions. However, heterogeneity across MRI field strengths and acquisition protocols limits the generalizability of existing methods. In this study, we formulate cranial CT synthesis as a modular, structurally coupled problem and propose a deep learning framework to improve robustness across heterogeneous MRI conditions. The model is designed to adapt to variations in field strength and imaging protocols while preserving anatomical consistency. Experiments on multi-site datasets demonstrate improved performance and generalization compared with conventional approaches. The proposed method enables reliable CT synthesis across heterogeneous MRI settings, supporting broader clinical translation.