MicroDiffuse3D: A Foundation Model for 3D Microscopy Imaging Restoration

Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computational challenges and the complexity of volumetric representation learning. In this work, we introduce a 3D foundation model for LSM data, pretrained on a large curated collection of 3D images spanning multiple organisms, stains, and imaging protocols. We learn transferable volumetric representations by jointly optimizing for masked reconstruction and image-text alignment. The pretrained backbone drastically reduces the annotation burden, enabling efficient, few-shot adaptation for varied downstream tasks. We evaluate this approach on downstream segmentation, classification, and deblurring. Our results demonstrate consistent improvements over baselines, (1) when measured using standard evaluation metrics and (2) when rigorously assessed by domain experts. This highlights the potential of foundation model pretraining to reduce annotation requirements while improving performance across diverse LSM analysis tasks. Pretrained model weights and code for pretraining and finetuning are publicly available: https://github.com/AdinaScheinfeld/lsm_fm_public_repo.git.

Digital pathology relies on high-resolution whole slide images for accurate diagnosis, yet limitations in imaging devices, storage, and transmission often make lower-resolution pathology images more common in clinical workflows. Current super-resolution techniques often tend to smooth diagnostically relevant morphology, leading to over-smoothed textures and semantic drift that compromise downstream clinical interpretation. To this end, we develop the Structural Semantic Synergy Diffusion Model (S3-Diff), a diffusion framework for high-fidelity super-resolution of pathological images. The core of S3-Diff is Specimen-aware Structural Anchoring (SSA), which combines prognosis-aware tissue support extracted by a fixed SAM with LR-HR gradient discrepancies to generate a specimen-specific structural anchor to preserve pathological morphology. Concurrently, we introduce Structure-guided Semantic Fidelity Tuning (SSFT) to adapt DINOv3 representations using SSA-derived structural supervision. SSFT combines the adapted semantic energy with LR-derived edge and grayscale cues. The resulting control guides denoising to suppress stochastic artifacts and maintain structural consistency. Extensive experimental results demonstrate that S3-Diff consistently outperforms state-of-the-art methods in both reconstruction quality and downstream survival analysis performance. The source code will be made public.

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.