SkelEM: Training-Signal Decoupling of Skeleton and Diffusion for Self-supervised Axial Super-Resolution in Volume Microscopy

Anisotropic volumetric acquisitions are common in clinical MRI and volume electron microscopy (vEM), where sparse through-plane sampling creates thick slices or sections that degrade orthogonal reformats and downstream analysis. We present CRIS, a cross-plane self-supervised framework for isotropic restoration without paired isotropic ground truth. CRIS casts 3D restoration as 2D stripe completion on orthogonal reformats of an isotropic grid: high-resolution in-plane slices are synthetically degraded and periodically masked for training, while at inference blank slices define the isotropic grid, two orthogonal reformats are restored, and predictions are fused by multi-view averaging. We evaluate CRIS on two MRI cohorts and two microscopy benchmarks up to 8x anisotropy. On brain MRI, CRIS achieves 32.921 +/- 0.436 dB PSNR and 0.963 +/- 0.003 SSIM, outperforming interpolation, ECLARE, SMORE4, SIMPLE, SA-INR, and ATME, and gives the best segmentation consistency (Dice 0.940 +/- 0.004, ASSD 0.245 +/- 0.014 mm, HD99 1.275 +/- 0.061 mm). On reference-free abdominal MRI, CRIS reduces FID/KID to 48.71/0.023, outperforming interpolation, ECLARE, SMORE4, and SIMPLE. On vEM, CRIS achieves 29.100 dB/0.830 3D PSNR/SSIM at 4x and 26.874 dB/0.722 at 8x on EPFL, and 21.935 +/- 0.437 dB/0.696 +/- 0.024 on noisy hemibrain data. In a dedicated robustness experiment, one variable-gap CRIS model evaluated across gap factors 3-7 and coronal, axial, and sagittal degradations maintained higher PSNR/SSIM than interpolation (36.36-31.14 dB and 0.977-0.932 vs. 33.07-27.85 dB and 0.951-0.853). These results support CRIS as a modality-flexible route to isotropic restoration without paired isotropic targets or configuration-specific retraining. Code is available at https://github.com/adi-hatav/CRIS.

Creating images from noise is image generation; reconstructing fine details from coarse inputs is super-resolution. Despite their practical differences, both can be understood as reversing information loss across scales. We introduce $\textbf{SKILD}$, a $\textbf{S}$cale-invariant $\textbf{K}$-Space $\textbf{I}$mage $\textbf{L}$earning $\textbf{D}$iffusion model that unifies generation and continuous super-resolution within a single unconditional framework. Both natural images and critical physical systems exhibit scale invariance, and we leverage it to design a forward process that attenuates image content from fine to coarse scales while injecting spectrum-matched Gaussian noise, making scale an explicit coordinate of the diffusion dynamics. The same trained reverse process performs generation and continuous super-resolution by varying only the starting timestep: $\textit{no task-specific architecture, no conditioning branch, no classifier-free guidance, no retraining per scale factor}$. Empirically, SKILD reaches FID $2.65$ and Inception Score $9.63$ on unconditional CIFAR-10, performs $2\times$--$8\times$ super-resolution on ImageNet from a single unconditional checkpoint while outperforming conditional models across perceptual metrics, and reconstructs critical Ising models whose connected four-point correlations closely track the ground truth.

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 $10\times$ 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.