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GEM: 3D Gaussian Splatting for Efficient and Accurate Cryo-EM Reconstruction

Cryo-electron microscopy (cryo-EM) has become a central tool for high-resolution structural biology, yet the massive scale of datasets (often exceeding 100k particle images) renders 3D reconstruction both computationally expensive and memory intensive. Traditional Fourier-space methods are efficient but lose fidelity due to repeated transforms, while recent real-space approaches based on neural radiance fields (NeRFs) improve accuracy but incur cubic memory and computation overhead. Therefore, we introduce GEM, a novel cryo-EM reconstruction framework built on 3D Gaussian Splatting (3DGS) that operates directly in real-space while maintaining high efficiency. Instead of modeling the entire density volume, GEM represents proteins with compact 3D Gaussians, each parameterized by only 11 values. To further improve the training efficiency, we designed a novel gradient computation to 3D Gaussians that contribute to each voxel. This design substantially reduced both memory footprint and training cost. On standard cryo-EM benchmarks, GEM achieves up to 48% faster training and 12% lower memory usage compared to state-of-the-art methods, while improving local resolution by as much as 38.8%. These results establish GEM as a practical and scalable paradigm for cryo-EM reconstruction, unifying speed, efficiency, and high-resolution accuracy. Our code is available at https://github.com/UNITES-Lab/GEM.

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