Pose estimation from unordered images is fundamental for 3D reconstruction, robotics, and scientific imaging. Recent geometric foundation models, such as DUSt3R, enable end-to-end dense 3D reconstruction but remain underexplored in scientific imaging fields like cryo-electron microscopy (cryo-EM) for near-atomic protein reconstruction. In cryo-EM, pose estimation and 3D reconstruction from unordered particle images still depend on time-consuming iterative optimization, primarily due to challenges such as low signal-to-noise ratios (SNR) and distortions from the contrast transfer function (CTF). We introduce CryoFastAR, the first geometric foundation model that can directly predict poses from Cryo-EM noisy images for Fast ab initio Reconstruction. By integrating multi-view features and training on large-scale simulated cryo-EM data with realistic noise and CTF modulations, CryoFastAR enhances pose estimation accuracy and generalization. To enhance training stability, we propose a progressive training strategy that first allows the model to extract essential features under simpler conditions before gradually increasing difficulty to improve robustness. Experiments show that CryoFastAR achieves comparable quality while significantly accelerating inference over traditional iterative approaches on both synthetic and real datasets.

Foundation models in computer vision have demonstrated exceptional performance in zero-shot and few-shot tasks by extracting multi-purpose features from large-scale datasets through self-supervised pre-training methods. However, these models often overlook the severe corruption in cryogenic electron microscopy (cryo-EM) images by high-level noises. We introduce DRACO, a Denoising-Reconstruction Autoencoder for CryO-EM, inspired by the Noise2Noise (N2N) approach. By processing cryo-EM movies into odd and even images and treating them as independent noisy observations, we apply a denoising-reconstruction hybrid training scheme. We mask both images to create denoising and reconstruction tasks. For DRACO's pre-training, the quality of the dataset is essential, we hence build a high-quality, diverse dataset from an uncurated public database, including over 270,000 movies or micrographs. After pre-training, DRACO naturally serves as a generalizable cryo-EM image denoiser and a foundation model for various cryo-EM downstream tasks. DRACO demonstrates the best performance in denoising, micrograph curation, and particle picking tasks compared to state-of-the-art baselines.