XPos3R: Cross-Modal Transformer for Intraoperative 2D/3D Registration

Intraoperative 2D/3D registration, which aligns live X-ray images with preoperative volumes, is essential for image-guided interventions. Previous regression-based methods suffer from limited generalization, thus requiring time-consuming patient-specific retraining. Inspired by recent geometry foundation models such as DUSt3R, we propose XPos3R, a generalizable pose regression method that eliminates preoperative preparation. Unlike existing geometry models designed for homogeneous inputs, XPos3R extends this paradigm to multi-modal inputs, namely 2D X-rays and 3D volumes. Specifically, we introduce an asymmetric encoder-decoder architecture that improves cross-modal feature alignment while maintaining computational efficiency. To scale training under limited medical data, we adopt an anatomy-specific data curation strategy and construct million-scale synthetic datasets. Evaluated on real-world benchmarks, a single pretrained XPos3R surpasses patient-specific methods in both accuracy and robustness. With test-time optimization completed in seconds, it further reduces the 3D error to <4 mm and the reprojection error to <1 mm. The strong generalization, accuracy, and efficiency of XPos3R highlight its clinical potential, while its asymmetric framework may inspire broader cross-modal vision geometry tasks.