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.
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.
Generating high-resolution 3D CT volumes with fine details remains challenging due to substantial computational demands and optimization difficulties inherent to existing generative models. In this paper, we propose the Pixel-Level Residual Diffusion Transformer (PRDiT), a scalable generative framework that synthesizes high-quality 3D medical volumes directly at voxel-level. PRDiT introduces a two-stage training architecture comprising 1) a local denoiser in the form of an MLP-based blind estimator operating on overlapping 3D patches to separate low-frequency structures efficiently, and 2) a global residual diffusion transformer employing memory-efficient attention to model and refine high-frequency residuals across entire volumes. This coarse-to-fine modeling strategy simplifies optimization, enhances training stability, and effectively preserves subtle structures without the limitations of an autoencoder bottleneck. Extensive experiments conducted on the LIDC-IDRI and RAD-ChestCT datasets demonstrate that PRDiT consistently outperforms state-of-the-art models, such as HA-GAN, 3D LDM and WDM-3D, achieving significantly lower 3D FID, MMD and Wasserstein distance scores.
Zhenkai Zhang, Markus Hiller, Krista A. Ehinger +1
Diffusion models produce high-quality synthetic data but suffer from slow inference. We propose 3D Variable-Step Denoising Diffusion Probabilistic Model (VS-DDPM) a framework engineered to maintain generative quality while accelerating inference by several factors. We tested our approach on four tasks (missing MRI, tumor removal, MRI-to-sCT, and CBCT-to-sCT) within the BraTS2025 and SynthRAD2025 challenges. Designed for high efficiency under hardware and time constrains imposed by both challenges. VS-DDPM achieved state-of-the-art (SOTA) performance in missing MRI synthesis, yielding Dice scores of 0.80, 0.83, and 0.88 for the enhancing tumor, tumor core, and whole tumor regions, respectively, alongside a structural similarity index (SSIM) of 0.95. For MRI tumor removal, the model attained a root mean squared error (RMSE) of 0.053, a peak signal-to-noise ratio (PSNR) of 26.77, and an SSIM of 0.918. While the framework demonstrated competitive performance in MRI-to-sCT and CBCT-to-sCT tasks, it did not reach SOTA benchmarks, potentially due to sensitivities in data pre and post-processing pipelines or specific loss function configurations. These results demonstrate that VS-DDPM provides a robust and tunable solution for high-fidelity 3D medical image synthesis. The code is available in https://github.com/andre-fs-ferreira/SynthRAD_by_Faking_it.