High-fidelity 3D MRI synthesis requires both globally coherent anatomy and fine-grained voxel-level detail. Although latent diffusion makes volumetric generation tractable, its image autoencoder introduces a reconstruction bottleneck that can limit the fine detail recoverable in the final volume. We present VoxStruct3D, a voxel-space flow-matching framework that directly models full-resolution MRI volumes using a clean-data prediction objective. Its Volumetric Voxel Generator (VVG) combines factorized 3D patch embedding with overlapping upsampling, time-modulated residual refinement, and skip fusion, enabling neighboring tokens to jointly reconstruct shared voxel regions and suppress patch-boundary artifacts. To complement direct voxel-space modeling with an explicit anatomical prior, we further introduce a Structure-First, Image-Follows (SFIF) strategy. A frozen pretrained 3D medical encoder and a StructVAE extract compact structure tokens that preserve dominant anatomy, while a structure-leading schedule keeps their trajectory ahead of the image trajectory. Patch-Aligned RoPE spatially aligns the unequal token grids, and asymmetric attention enforces one-way guidance from structure to image. Experiments on pathological and healthy T1-weighted brain MRI datasets show that VoxStruct3D achieves the strongest overall performance across feature-distribution alignment, sample diversity, and perceptual quality, producing anatomically coherent and visually realistic volumes.
Three-dimensional (3D) medical image enhancement, including denoising and super-resolution, is critical for clinical diagnosis in CT, PET, and MRI. Although diffusion models have shown remarkable success in 2D medical imaging, scaling them to high-resolution 3D volumes remains computationally prohibitive due to lengthy diffusion trajectories over high-dimensional volumetric data. We observe that in conditional enhancement, strong anatomical priors in the degraded input render dense noise schedules largely redundant. Leveraging this insight, we propose a sparse voxel-space diffusion framework that trains and samples on a compact set of uniformly subsampled timesteps. The network predicts clean data directly on the data manifold, supervised in velocity space for stable gradient scaling. A lightweight Structure-aware Trajectory Modulation (STM) module recalibrates time embeddings at each network block based on local anatomical content, enabling structure-adaptive denoising over the shared sparse schedule. Operating directly in voxel space, our framework preserves fine anatomical detail without lossy compression while achieving up to 10× training acceleration. Experiments on four datasets spanning CT, PET, and MRI demonstrate state-of-the-art performance on both denoising and super-resolution tasks. Our code is publicly available at: https://github.com/mirthAI/sparse-3d-diffusion.
Large and demographically balanced datasets are essential for reliable neuroimaging biomarkers. Full-resolution 3D brain MRI synthesis can support data augmentation in this setting, but existing approaches either incur prohibitive computational cost at volumetric scale or rely on lossy latent compression that may compromise anatomical detail. As a result, practical 3D generative augmentation often requires specialized compute infrastructure. We propose WaveDiT, a conditional flow matching framework operating in the coefficient space of a 3D Haar Discrete Wavelet Transform. The model combines factorized spatio-depth attention with band-wise heteroscedastic uncertainty modeling derived from higher-order wavelet statistics. Predicted log-variance is integrated directly into both the flow objective and conditioning pathway, enabling adaptive precision consistent with the heavy-tailed and input-dependent variance structure of anatomical detail. This formulation supports full-resolution 3D synthesis under practical memory and time constraints on a single modern GPU. Evaluation on a multi-site cohort demonstrates improved alignment between generated and real MRI distributions, together with enhanced downstream brain age prediction and region-level anatomical agreement relative to diffusion, latent, and wavelet-based baselines. Code is available at https://github.com/sisinflab/WaveDiT
Danilo Danese, Angela Lombardi, Giuseppe Fasano +2
Predicting future structural MRI of a brain is challenging because longitudinal changes are often subtle and confined to specific anatomical regions, while most subject-specific brain structure remains stable over time. An effective model should therefore preserve global brain structural consistency while remaining sensitive to fine-grained disease progression. Existing latent-space-based methods improve computational efficiency, but suffer from information loss during their compression-reconstruction procedure. In contrast, direct voxel-space methods avoid latent reconstruction but commonly use a unified prediction pathway to model brain structure and progression-related changes. Subtle local changes may therefore be overshadowed by the dominant stable brain structure. To address these challenges, we propose ProgFormer, a hierarchical voxel-space Diffusion Transformer for longitudinal brain MRI prediction. ProgFormer uses a coarse pathway to perform the primary volumetric prediction from 3D patch tokens. This pathway models overall brain structure and longitudinal context. The fine pathway then uses the coarse representations as spatio-temporal grounding for voxel-level refinement within individual patches. The two pathways jointly estimate a velocity field directly in voxel space through conditional flow matching, enabling end-to-end prediction without a separately learned image autoencoder. The predicted future scan is then generated from Gaussian noise by integrating the estimated velocity field over a sequence of Euler steps. Extensive experimental results on three widely used benchmarks, ADNI, AIBL, and OASIS, under both pairwise and trajectory settings demonstrate favourable performance compared against several state-of-the-art methods.