X-ray angiography relies on iodinated contrast agents to visualize vascular structures during image-guided interventions. However, contrast administration carries risks of adverse events, motivating the development of contrast-free alternatives. Generating X-ray angiograms directly from non-contrast X-ray images offers a potential solution, but existing approaches remain limited by (i) insufficient control over vascular localization and (ii) inefficient modeling of redundant background content. To address these challenges, we propose VeCAS, a two-stage vessel-focused contrast-free angiogram synthesis framework that separates vascular structure localization from angiographic appearance synthesis. In Stage I, a discriminative model localizes vascular structures in non-contrast X-ray images, while cross-modality latent distillation transfers vessel-sensitive knowledge from X-ray angiograms during training. In Stage II, a vessel-focused inpainting model synthesizes angiographic appearance within the localized vascular regions while preserving the non-vascular background. Experiments on an in-house lower-limb vascular intervention dataset show that VeCAS outperforms the comparison methods in terms of vascular structural fidelity and image quality. Visual Turing tests and physician assessments indicate the perceptual realism of the synthesized angiograms. In addition, robotic guidewire navigation experiments in vascular phantoms show that VeCAS guidance reduces the time to target by 41.4% and the number of operation steps by 40.7% compared with non-contrast guidance. Together, these results suggest the potential of VeCAS to serve as ``meta contrast agent'' for vascular interventions.
Intraoperative 2D/3D registration aligns preoperative CT volumes with intraoperative X-ray or fluoroscopic images and is essential for image-guided interventions. Recent learning-based and differentiable registration methods have shown promising accuracy, especially in patient-specific settings where abundant digitally reconstructed radiographs (DRRs) can be synthesized from the target CT. However, training a separate patient-specific model from scratch for every new patient is computationally inefficient and limits practical deployment. In this work, we propose an efficient patient-specific 2D/3D registration framework based on patient-agnostic synthetic pretraining and spherical similarity learning. The model is first pretrained on synthetic DRRs generated from multiple CT volumes to learn transferable pose-sensitive representations, and is then adapted to a new patient using only a limited number of synthetic projections from the target CT. To improve synthetic-to-real robustness without requiring anatomical labels, we introduce a segmentation-free domain randomization strategy that perturbs image intensity, projection physics, field-of-view, occlusion, and fluoroscopic artifacts. The adapted model provides an initial pose estimate, which is further refined using spherical similarity learning and differentiable Levenberg-Marquardt optimization. Experiments on multiple anatomical datasets evaluate whether patient-agnostic synthetic pretraining can improve the efficiency of patient-specific registration, with particular focus on the trade-off between adaptation cost and registration accuracy. The results demonstrate that patient-agnostic synthetic pretraining can significantly reduce patient-specific training requirements while preserving accurate intraoperative 2D/3D registration.