CAPS: Clinically-Verifiable Anatomy-Prioritized Synthesis for Missing MRI Imputation in Brain Tumor Segmentation
Organizations: Universidad Autónoma de Madrid, Department of Electronic Technology and Communications, Madrid, Spain · RIKEN Center for Integrative Medical Sciences, Medical Data Deep Learning Team, Tokyo, Japan · Hospital Universitario La Princesa, Diagnostic Radiology Department, Madrid, Spain
Abstract
Multi-parametric MRI is the gold standard for neuro-oncology, yet acquiring complete 4-modality protocols may be unfeasible in real-world clinical practice. When handling missing modalities, existing automated systems force a critical compromise: robust segmenters operate as uninterpretable "black boxes" that bypass image generation, while standard synthesis models often produce blurry reconstructions lacking diagnostic reliability. To address this issue, we propose CAPS, a Clinically-Verifiable Anatomy-Prioritized Synthesis framework that reconciles computational precision with clinical transparency. Our multi-modal generative architecture is driven by a hybrid objective function (L_1 + L_AFP + L_DualDice) that explicitly enforces the preservation of deep anatomical features and strict topological boundaries, rather than relying solely on pixel-wise optimization. Evaluated comprehensively on the BraTS Adult Glioma dataset, the framework achieves superior synthesis fidelity across intensity-based metrics, and demonstrates robust downstream segmentation performance (82.38% mean Dice), successfully restoring verifiable visual context. Furthermore, the framework exhibits exceptional zero-shot cross-domain generalization, maintaining high structural fidelity across completely unseen Meningioma, Pediatric, and Sub-Saharan African cohorts without domain-specific adaptation. Finally, a blinded radiological assessment confirms that our anatomy-aware approach significantly enhances both perceived image quality and clinical utility, providing clinicians with the reliable visual evidence required to trust downstream automated workflows.
Figures & tables
| Dice ( ) | HD95 ( ) | |||||||
| Strategy | ENH | TC | WT | Mean | ENH | TC | WT | Mean |
| Reference (All Real) | 81.47 | 86.27 | 92.22 | 86.65 | 21.56 | 9.67 | 4.98 | 12.07 |
| Missing T1n | ||||||||
| Zero Imputation | 79.60 | 83.55 | 91.59 | 84.91 | 22.37 | 12.84 | 5.71 | 13.64 |
| Trained with Dropout | 79.04 | 86.77 | 92.40 | 86.07 | 30.42 | 8.31 | 4.46 | 14.40 |
| Synthesis Baseline | 79.89 | 84.97 | 90.87 | 85.24 | 24.48 | 12.60 | 8.06 | 15.05 |
| Dice ( ) | HD95 ( ) | IQM | ||||||||
| Network | ENH | TC | WT | Mean | ENH | TC | WT | Mean | NMSE ( ) | PSNR ( ) |
| Reference (All Real) | 81.47 | 86.27 | 92.22 | 86.65 | 21.56 | 9.67 | 4.98 | 12.07 | - | - |
| nnU-net | 52.27 | 70.27 | 90.03 | 70.86 | 41.44 | 18.83 | 7.37 | 22.55 | 0.0261 | 27.60 |
| nnResU-net | 54.47 | 71.50 | 90.01 | 71.99 | 38.44 | 19.22 | 7.47 | 21.71 | 0.0256 | 27.72 |
| nnResUnet + trilinear decoder | 54.54 | 71.46 | 90.26 | 72.09 | 41.13 | 17.42 | 7.47 | 22.01 | 0.0241 | 28.05 |
| Dice ( ) | HD95 ( ) | IQM | ||||||||
| Loss | ENH | TC | WT | Mean | ENH | TC | WT | Mean | NMSE ( ) | PSNR ( ) |
| Reference (All Real) | 81.47 | 86.27 | 92.22 | 86.65 | 21.56 | 9.67 | 4.98 | 12.07 | - | - |
| L1 | 54.54 | 71.46 | 90.26 | 72.09 | 41.13 | 17.42 | 7.47 | 22.01 | 0.0241 | 28.05 |
| L1 + | 54.83 | 73.70 | 90.97 | 73.17 | 39.74 | 15.32 | 7.01 | 20.69 | 0.0286 | 26.95 |
| L1 + | 54.93 | 76.99 | 91.17 | 74.36 | 38.21 | 13.07 | 5.94 | 19.07 | 0.0290 | 26.88 |
| L1 + AFP | 55.33 | 73.46 | 91.46 | 74.42 | 37.59 | 14.53 | 6.26 | 19.46 | 0.0240 | 27.83 |
| Dice ( ) | HD95 ( ) | |||||||
| Training Strategy | ENH | TC | WT | Mean | ENH | TC | WT | Mean |
| Reference (All Real) | 81.47 | 86.27 | 92.22 | 86.65 | 21.56 | 9.67 | 4.98 | 12.07 |
| 25% Missing Modality Ratio | ||||||||
| Random Dropout | 57.39 | 77.10 | 90.89 | 75.13 | 40.19 | 13.47 | 6.24 | 19.97 |
| Synthetic (from scratch) | 56.98 | 77.55 | 92.05 | 75.53 | 35.98 | 10.85 | 4.44 | 17.09 |
| Synthetic (FT) | 56.76 | 76.40 | 90.13 | 74.43 | 37.56 | 14.89 | 11.44 | 21.30 |
| Dice ( ) | HD95 ( ) | IQM | ||||||||
| ENH | TC | WT | Mean | ENH | TC | WT | Mean | NMSE ( ) | PSNR ( ) | |
| Missing T1n | 80.58 | 85.87 | 91.24 | 85.90 | 22.56 | 11.07 | 6.02 | 13.22 | 0.0160 | 28.99 |
| Missing T1c | 57.95 | 77.59 | 91.86 | 75.80 | 36.10 | 10.90 | 4.63 | 17.21 | 0.0259 | 27.32 |
| Missing T2w | 79.22 | 85.46 | 90.69 | 85.12 | 22.99 | 11.59 | 10.91 | 15.16 | 0.0530 | 26.18 |
| Missing T2f | 73.58 | 83.93 | 90.57 | 82.69 | 36.93 | 10.09 | 7.68 | 18.23 | 0.0453 | 25.34 |
| Average | 72.83 | 83.21 | 91.09 | 82.38 | 29.65 | 10.91 | 7.31 | 15.96 | 0.0351 | 26.96 |
| IQM | Synthesis Type | |||||
| Method | Eval. Split | NMSE | PSNR | SSIM % | 1-to-1 | 3-to-1 |
| Evaluated Scenarios: Missing T2w, T2f | ||||||
| Pix2Pix Isola et al. (2017) | Official Val. | 0.105 | 24.89 | 87.05 | ||
| CycleGAN Zhu et al. (2017) | Official Val. | 0.145 | 23.62 | 82.85 | ||
| EaGAN Yu et al. (2019) | Official Val. | 0.103 | 24.73 | 86.65 | ||
| ALDM Kim and Park (2024) | Official Val. | 0.089 | 25.45 | 88.55 | ||
| Method | ENH | TC | WT | Mean |
| Robust Segmentation: | ||||
| Random Dropout | 74.29 | 84.42 | 91.63 | 83.45 |
| U-HVED Dorent et al. (2019) | 70.88 | 80.75 | 88.63 | 80.08 |
| mmFormer Zhang et al. (2022) | 80.23 | 88.38 | 92.20 | 86.93 |
| Sfusion Liu et al. (2023) | 77.95 | 86.60 | 91.05 | 85.20 |
| IM-Fuse Pipoli et al. (2025) | 80.73 | 88.95 | 92.35 | 87.34 |
| Meningioma | Pediatric Glioma | Sub-Saharan Glioma | ||||
| Missing Modality | NMSE ( ) | PSNR ( ) | NMSE ( ) | PSNR ( ) | NMSE ( ) | PSNR ( ) |
| 4MRI Real | 0.0 | 0.0 | 0.0 | |||
| Missing T1n | 0.0248 | 27.72 | 0.0216 | 28.05 | 0.0215 | 27.56 |
| Missing T1c | 0.0505 | 25.41 | 0.0330 | 25.93 | 0.0272 | 25.91 |
| Missing T2w | 0.0534 | 26.21 | 0.0648 | 25.20 | 0.0507 | 25.67 |
| Missing T2f | 0.0360 | 25.63 | 0.0266 | 26.46 | 0.0279 | 26.55 |
Medical Image Synthesis
Medical image synthesis creates, translates, reconstructs, and edits clinical images to fill missing data and support analysis.
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