CryoCCD: Conditional Cycle-consistent Diffusion with Biophysical Modeling for Cryo-EM Synthesis

Cryo-electron microscopy (cryo-EM) offers near-atomic resolution imaging of macromolecules, but developing robust models for downstream analysis is hindered by the scarcity of high-quality annotated data. While synthetic data generation has emerged as a potential solution, existing methods often fail to capture both the structural diversity of biological specimens and the complex, spatially varying noise inherent in cryo-EM imaging. To overcome these limitations, we propose CryoCCD, a synthesis framework that integrates biophysical modeling with generative techniques. Specifically, CryoCCD produces multi-scale cryo-EM micrographs that reflect realistic biophysical variability through compositional heterogeneity, cellular context, and physics-informed imaging. To generate realistic noise, we employ a conditional diffusion model, enhanced by cycle consistency to preserve structural fidelity and mask-aware contrastive learning to capture spatially adaptive noise patterns. Extensive experiments show that CryoCCD generates structurally accurate micrographs and enhances performance in downstream tasks, outperforming state-of-the-art baselines in both particle picking and reconstruction.

Enhancing Weakly Supervised 3D Medical Image Segmentation through Probabilistic-aware Learning

3D medical image segmentation is a challenging task with crucial implications for disease diagnosis and treatment planning. Recent advances in deep learning have significantly enhanced fully supervised medical image segmentation. However, this approach heavily relies on labor-intensive and time-consuming fully annotated ground-truth labels, particularly for 3D volumes. To overcome this limitation, we propose a novel probabilistic-aware weakly supervised learning pipeline, specifically designed for 3D medical imaging. Our pipeline integrates three innovative components: a probability-based pseudo-label generation technique for synthesizing dense segmentation masks from sparse annotations, a Probabilistic Multi-head Self-Attention network for robust feature extraction within our Probabilistic Transformer Network, and a Probability-informed Segmentation Loss Function to enhance training with annotation confidence. Demonstrating significant advances, our approach not only rivals the performance of fully supervised methods but also surpasses existing weakly supervised methods in CT and MRI datasets, achieving up to 18.1% improvement in Dice scores for certain organs. The code is available at https://github.com/runminjiang/PW4MedSeg.