An Uncertainty Estimation Framework for Dose Accumulation in Adaptive Radiotherapy: Application to CBCT-Guided Radiotherapy for Cervical Cancer

Background and purpose: oART enables daily plan adaptation to interfraction anatomical variations, but cumulative dose estimation remains limited by DIR, segmentation, and anatomical uncertainties. We introduce IMPACT-DoseAcc, an uncertainty-aware dose accumulation framework, within IMPACT for semantic feature-driven image analysis. The framework is modality- and disease-agnostic and is applied to CBCT-guided oART for cervical cancer (LACC). Material and Methods: Nine LACC patients were retrospectively analyzed using daily CBCT-derived virtual CTs for dose recalculation. IMPACT-DoseAcc focuses on uncertainty from DIR, without modeling vCT-generation uncertainty. Two DIR uncertainty strategies were tested within IMPACT-Reg: a Bayesian segmentation-guided approach using one probabilistic model to quantify anatomical uncertainty, and an ensemble of segmentation models targeting structures to capture epistemic variability. Voxel-wise uncertainty maps were propagated through dose warping and accumulation to generate probabilistic dose-volume histograms. Ensemble uncertainty was quantified from voxel-wise standard deviation across deformation fields, and geometric error was assessed using surface distance between warped and validated contours. Anatomical-variability weighting refined aggregation. Results: Ensemble DIR uncertainty correlated with geometric error, with Pearson coefficients of 0.63 for CTVt and 0.66 for bladder. For CTVt, pDVHs achieved 96.3 +/- 3.9% coverage, showing calibration of propagated uncertainty. Weighting stabilized estimates across fractions and organs. Conclusions: IMPACT-DoseAcc propagates registration-driven uncertainty to cumulative dose metrics, improving interpretation of accumulated dose under anatomical variations. Its 3DSlicer integration supports reproducible, uncertainty-informed ART workflows.

Generating synthetic computed tomography for radiotherapy: SynthRAD2025 challenge report

Radiation therapy (RT) requires precise dose delivery over multiple fractions, with CT fundamental for treatment planning due to its electron density information. Repeated CT acquisitions impose radiation exposure and logistical burdens, MRI lacks electron density, and cone-beam CT (CBCT) requires correction for dose calculation. Synthetic CT (sCT) generation addresses these by converting MRI or CBCT into CT-equivalent images with accurate Hounsfield Unit (HU) values, enabling MRI-only RT and CBCT-based adaptive workflows. Building on SynthRAD2023, SynthRAD2025 benchmarked sCT methods on 2,362 patients from five European centers across head and neck, thorax, and abdomen. Two tasks: MRI-to-CT (890 cases) and CBCT-to-CT (1,472 cases), evaluated via image similarity (MAE, PSNR, MS-SSIM), segmentation (Dice, HD95), and dosimetric metrics from photon and proton plans. With 803 participants and 12/13 valid submissions, Task 1 top performance reached MAE $64.8\pm21.3$ HU, PSNR $\sim$30 dB, MS-SSIM $\sim$0.936, Dice 0.79, photon $γ_{2\%/2\text{mm}}>98\%$, proton $γ\approx85\%$. Task 2 improved: MAE $48.3\pm13.4$ HU, PSNR 32.6 dB, MS-SSIM 0.968, Dice 0.86, photon $γ>99\%$, proton $γ\approx89\%$. Strong image--segmentation correlations ($ρ=0.78$--$0.79$) but moderate dose correlations confirmed image quality is insufficient as a dosimetric surrogate. Head-and-neck cases were most consistent; thoracic and abdominal cases showed greater variability. Residual errors at tissue interfaces propagate along beam paths, affecting proton dose more than photon. SynthRAD2025 demonstrates that deep learning yields clinically relevant sCTs, especially for CBCT-to-CT, while identifying persistent MRI-to-CT challenges and underscoring dose-based evaluation as essential for clinical validation.

Fine-tuning Segment Anything for Real-Time Tumor Tracking in Cine-MRI

In this work, we address the TrackRAD2025 challenge of real-time tumor tracking in cine-MRI sequences of the thoracic and abdominal regions under strong data scarcity constraints. Two complementary strategies were explored: (i) unsupervised registration with the IMPACT similarity metric and (ii) foundation model-based segmentation leveraging SAM 2.1 and its recent variants through prompt-based interaction. Due to the one-second runtime constraint, the SAM-based method was ultimately selected. The final configuration used SAM2.1 b+ with mask-based prompts from the first annotated slice, fine-tuned solely on the small labeled subset from TrackRAD2025. Training was configured to minimize overfitting, using 1024x1024 patches (batch size 1), standard augmentations, and a balanced Dice + IoU loss. A low uniform learning rate (0.0001) was applied to all modules (prompt encoder, decoder, Hiera backbone) to preserve generalization while adapting to annotator-specific styles. Training lasted 300 epochs (~12h on RTX A6000, 48GB). The same inference strategy was consistently applied across all anatomical sites and MRI field strengths. Test-time augmentation was considered but ultimately discarded due to negligible performance gains. The final model was selected based on the highest Dice Similarity Coefficient achieved on the validation set after fine-tuning. On the hidden test set, the model reached a Dice score of 0.8794, ranking 6th overall in the TrackRAD2025 challenge. These results highlight the strong potential of foundation models for accurate and real-time tumor tracking in MRI-guided radiotherapy.

Implicit Shape-Prior for Few-Shot Assisted 3D Segmentation

The objective of this paper is to significantly reduce the manual workload required from medical professionals in complex 3D segmentation tasks that cannot be yet fully automated. For instance, in radiotherapy planning, organs at risk must be accurately identified in computed tomography (CT) or magnetic resonance imaging (MRI) scans to ensure they are spared from harmful radiation. Similarly, diagnosing age-related degenerative diseases such as sarcopenia, which involve progressive muscle volume loss and strength, is commonly based on muscular mass measurements often obtained from manual segmentation of medical volumes. To alleviate the manual-segmentation burden, this paper introduces an implicit shape prior to segment volumes from sparse slice manual annotations generalized to the multi-organ case, along with a simple framework for automatically selecting the most informative slices to guide and minimize the next interactions. The experimental validation shows the method's effectiveness on two medical use cases: assisted segmentation in the context of at risks organs for brain cancer patients, and acceleration of the creation of a new database with unseen muscle shapes for patients with sarcopenia.

Calibration and Uncertainty for multiRater Volume Assessment in multiorgan Segmentation (CURVAS) challenge results

Deep learning (DL) has become the dominant approach for medical image segmentation, yet ensuring the reliability and clinical applicability of these models requires addressing key challenges such as annotation variability, calibration, and uncertainty estimation. This is why we created the Calibration and Uncertainty for multiRater Volume Assessment in multiorgan Segmentation (CURVAS), which highlights the critical role of multiple annotators in establishing a more comprehensive ground truth, emphasizing that segmentation is inherently subjective and that leveraging inter-annotator variability is essential for robust model evaluation. Seven teams participated in the challenge, submitting a variety of DL models evaluated using metrics such as Dice Similarity Coefficient (DSC), Expected Calibration Error (ECE), and Continuous Ranked Probability Score (CRPS). By incorporating consensus and dissensus ground truth, we assess how DL models handle uncertainty and whether their confidence estimates align with true segmentation performance. Our findings reinforce the importance of well-calibrated models, as better calibration is strongly correlated with the quality of the results. Furthermore, we demonstrate that segmentation models trained on diverse datasets and enriched with pre-trained knowledge exhibit greater robustness, particularly in cases deviating from standard anatomical structures. Notably, the best-performing models achieved high DSC and well-calibrated uncertainty estimates. This work underscores the need for multi-annotator ground truth, thorough calibration assessments, and uncertainty-aware evaluations to develop trustworthy and clinically reliable DL-based medical image segmentation models.

IMPACT: A Generic Semantic Loss for Multimodal Medical Image Registration

Image registration is fundamental in medical imaging, enabling precise alignment of anatomical structures for diagnosis, treatment planning, image-guided treatment or longitudinal monitoring. This work introduces IMPACT (Image Metric with Pretrained model-Agnostic Comparison for Transmodality registration), a generic semantic similarity metric designed for seamless integration into diverse image registration frameworks (such as Elastix and Voxelmorph). It compares deep learning-based features extracted from medical images without requiring task-specific training, ensuring broad applicability across various modalities. By leveraging the features of the large-scale pretrained TotalSegmentator models and the ability to integrate Segment Anything Model (SAM) and other large-scale segmentation networks, this approach offers significant advantages. It provides robust, scalable, and efficient solutions for multimodal image registration. The IMPACT loss was evaluated on five challenging registration tasks involving thoracic CT/CBCT, and pelvic MR/CT datasets. Quantitative metrics, such as Target Registration Error and Dice Similarity Coefficient, demonstrated significant improvements in anatomical alignment compared to baseline methods. Qualitative analyses further confirmed the increased robustness of the proposed metric in the face of noise, artifacts, and modality variations. IMPACT's versatility and efficiency make it a valuable tool for advancing registration performance in clinical and research applications, addressing critical challenges in multimodal medical imaging.