Organizations: State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China · School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China · School of Advanced Interdisciplinary Sciences, University of Chinese Academy of Sciences, Beijing 101408, China · Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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.
Figures & tables
Fig. 1: Iodinated Contrast Agent vs . Meta Contrast Agent. Top: In conventional X-ray angiography, iodinated contrast agents are injected to enhance vessel visibility, but their use may introduce contrast-related risks, such as kidney injury and allergic reactions. Bottom: The proposed meta contrast agent uses a trained deep neural network to synthesize X-ray angiograms from non-contrast X-ray images, providing a computational alternative with the potential to reduce contrast administration and improve procedural efficiency.
Fig. 2: Overview of VeCAS. VeCAS performs contrast-free angiogram synthesis using a two-stage framework. Stage I: A vascular structure localization model predicts the vessel mask from a non-contrast X-ray image. Stage II: A vessel-focused inpainting model synthesizes angiographic appearance within the predicted vascular regions while preserving the non-vascular background from the input image.
Fig. 3: Stage I: Cross-Modality Latent Distillation for Vascular Structure Localization. A frozen angiogram-domain segmentation model DA(EA(⋅)) provides vessel-sensitive multi-scale features from X-ray angiograms. The trainable non-contrast encoder EN(⋅) and multi-scale predictor P(⋅) learn to predict angiogram-domain latent features from non-contrast X-ray images. The predicted features are then decoded by the frozen decoder DA(⋅) for vessel mask prediction.
Fig. 4: Stage II: Vessel-Focused Inpainting. (a) Training: A vessel-focused denoising loss restricts the diffusion learning objective to vascular regions, encouraging the model to learn angiographic vessel appearance rather than redundant background reconstruction. (b) Inference: At each reverse diffusion step, the denoised vascular output is fused with the forward-diffused non-contrast X-ray image according to the predicted vessel mask from Stage I, thereby synthesizing contrast-enhanced appearance while preserving the non-vascular background.
Metric
R 1
R 2
R 3
R 4
mean±std
Sen. (%)
62.00
76.00
94.00
78.00
77.50±13.10
Spe. (%)
50.00
52.00
62.00
78.00
60.50±12.79
Acc. (%)
56.00
64.00
78.00
78.00
69.00±10.89
Positives: Real X-ray angiograms.
Negatives: Synthesized X-ray angiograms.
TABLE I: Results of the Visual Turing Test. Sensitivity (Sen.), specificity (Spe.), and accuracy (Acc.) are reported for each reader.
Fig. 5: Physician Assessments of Synthesized Angiograms. Three physicians independently scored the synthesized angiograms using three criteria: vascular morphological realism (VMR), contrast opacification realism (COR), and procedural usability (PU).
Method
DSC (%) ↑
clDice (%) ↑
Generative Models
Pix 2 Pix [ 20 ] [ CVPR ’17]
9.75±0.92∗∗∗
9.50±1.10∗∗∗
CycleGAN [ 21 ] [ ICCV ’17]
2.30±2.47∗∗∗
2.89±3.42∗∗∗
ResViT [ 27 ] [ TMI ’22]
37.03±7.09∗∗∗
42.69±7.93∗∗∗
BBDM [ 31 ] [ CVPR ’23]
5.43±1.67∗∗∗
5.38±1.86∗∗∗
ControlNet [ 33 ] [ ICCV ’23]
8.93±0.64∗∗∗
8.49±0.76∗∗∗
TABLE II: Quantitative comparison of different methods for Stage I. Results are reported as “ mean±std ” over five-fold cross-validation. The best and second-best results are highlighted in bold and underlined , respectively. Statistical significance against VeCAS is assessed using Wilcoxon signed-rank tests on patient-level scores ( ∗ : p<0.05 , ∗∗ : p<0.01 , ∗∗∗ : p<0.001 ).
Method
DSC (%) ↑
clDice (%) ↑
PSNR (dB) ↑
SSIM ↑
Pix 2 Pix [ 20 ] [ CVPR ’17]
13.11±2.26∗∗∗
14.78±2.46∗∗∗
36.06±1.20∗∗∗
0.9355±0.0173∗∗∗
CycleGAN [ 21 ] [ ICCV ’17]
26.41±4.07∗∗∗
31.93±5.05∗∗∗
35.71±0.74∗∗∗
0.9498±0.0075∗∗∗
CUT [ 25 ] [ ECCV ’20]
26.72±2.96∗∗∗
32.13±3.71∗∗∗
35.34±0.51∗∗∗
0.9015±0.0574∗∗∗
RegGAN [ 26 ] [ NeurIPS ’21]
35.60±4.75∗∗∗
41.78±6.33∗∗∗
33.27±1.16∗∗∗
0.9430±0.0065∗∗∗
ResViT [ 27 ] [ TMI ’22]
31.06±3.96∗∗∗
35.78±5.20∗∗∗
33.56±1.01∗∗∗
0.9400±0.0080∗∗∗
BBDM [ 31 ] [ CVPR ’23]
30.80±3.95∗∗∗
36.54±5.23∗∗∗
37.67±0.55
0.9488±0.0201∗∗∗
TABLE III: Quantitative comparison of different methods for Stage I + II. Results are reported as “ mean±std ” over five-fold cross-validation. The best and second-best results are highlighted in bold and underlined , respectively. Statistical significance against VeCAS is assessed using Wilcoxon signed-rank tests on patient-level scores ( ∗ : p<0.05 , ∗∗ : p<0.01 , ∗∗∗ : p<0.001 ).
Lseg
Lpred
DSC (%) ↑
clDice (%) ↑
✗
✓
29.49±3.53
35.52±2.74
✓
✗
51.49±3.47
59.66±4.63
✓
✓
52.56±3.32
60.62±4.42
TABLE IV: Ablation study of the distillation loss Ldistill in Stage I. The best and second-best results are highlighted in bold and underlined , respectively.
Fig. 6: Qualitative Results of the Complete Pipeline (Stage I + II). Compared with baseline methods, VeCAS synthesizes clearer and more continuous vascular structures while preserving the non-vascular background. Most baseline methods retain the background appearance but produce weak, incomplete, or barely visible vessels.
Fig. 7: Error Propagation Analysis under Different Mask Conditions. Stage II is evaluated using predicted masks from VeCAS, perturbed ground-truth masks, and oracle ground-truth masks to analyze how mask quality affects performance.
Vessel-focused
DSC (%) ↑
clDice (%) ↑
PSNR (dB) ↑
SSIM ↑
Loss
Sampling
✗
✗
11.43±3.76
12.55±4.23
29.69±0.34
0.9257±0.0152
✗
✓
11.38±3.03
11.89±3.56
36.19±0.93
0.9508±0.0178
✓
✗
20.51±4.32
22.96±5.08
31.66±0.58
0.9322±0.0169
✓
✓
42.27±4.99
47.70±6.29
36.78±0.91
0.9537±0.0183
TABLE V: Ablation study of the vessel-focused design in Stage II. The best and second-best results are highlighted in bold and underlined , respectively.
Fig. 8: Phantom Experiment. (a) Phantom experimental setup. (b) Navigation efficiency under different guidance conditions, evaluated by time to target and the number of operation steps. ❶ non-contrast guidance, ❷ VeCAS guidance, and ❸ contrast guidance.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Scottsdale, Arizona, USA · School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA