CryoSplat: Gaussian Splatting for Cryo-EM Homogeneous Reconstruction

TL;DR

CryoSplat introduces a novel GMM-based method that integrates Gaussian splatting with cryo-EM physics, enabling efficient 3D reconstruction directly from raw particle images without external initialization.

Contribution

It develops an orthogonal projection-aware Gaussian splatting tailored for cryo-EM, improving stability and efficiency in homogeneous reconstruction from raw data.

Findings

Outperforms baseline methods on real datasets

Enables stable reconstruction from random initialization

Validates effectiveness and robustness of cryoSplat

Abstract

As a critical modality for structural biology, cryogenic electron microscopy (cryo-EM) facilitates the determination of macromolecular structures at near-atomic resolution. The core computational task in single-particle cryo-EM is to reconstruct the 3D electrostatic potential of a molecule from noisy 2D projections acquired at unknown orientations. Gaussian mixture models (GMMs) provide a continuous, compact, and physically interpretable representation for molecular density and have recently gained interest in cryo-EM reconstruction. However, existing methods rely on external consensus maps or atomic models for initialization, limiting their use in self-contained pipelines. In parallel, differentiable rendering techniques such as Gaussian splatting have demonstrated remarkable scalability and efficiency for volumetric representations, suggesting a natural fit for GMM-based cryo-EM reconstruction. However, off-the-shelf Gaussian splatting methods are designed for photorealistic view synthesis and remain incompatible with cryo-EM due to mismatches in the image formation physics, reconstruction objectives, and coordinate systems. Addressing these issues, we propose cryoSplat, a GMM-based method that integrates Gaussian splatting with the physics of cryo-EM image formation. In particular, we develop an orthogonal projection-aware Gaussian splatting, with adaptations such as a view-dependent normalization term and FFT-aligned coordinate system tailored for cryo-EM imaging. These innovations enable stable and efficient homogeneous reconstruction directly from raw cryo-EM particle images using random initialization. Experimental results on real datasets validate the effectiveness and robustness of cryoSplat over representative baselines. The code will be released at https://github.com/Chen-Suyi/cryosplat.