A practical probabilistic framework for deformable image registration uncertainty in radiotherapy dose propagation
Authors: Stefan Heldmann, Sven Kuckertz, Nasim Givehchi, Thomas Coradi, Mikel Byrne, Ben Archibald-Heeren, Nils Papenberg
Organizations: Fraunhofer Institute for Digital Medicine MEVIS, Lübeck, Germany · Varian, a Siemens Healthineers company, Dättwil, Switzerland · Icon Group, South Brisbane, QLD, Australia
Deformable image registration (DIR) is widely used in radiotherapy for dose propagation and accumulation, but uncertainty in the underlying deformation can substantially affect clinically relevant dose estimates. We present a practical probabilistic framework for propagating DIR uncertainty to voxel-wise dose statistics and dose-volume histograms (DVHs). The method models the mapped correspondence at each voxel as a random variable governed by a transparent local certainty map that can be defined by simple safety margins, structure-boundary mismatch, or structure-wise conservative uncertainty values. This yields interpretable quantities such as dose probabilities, expected dose, confidence bounds, and induced DVH envelopes. The framework is designed to remain lightweight and interpretable: it avoids complex biomechanical or ensemble-based uncertainty models and instead emphasizes simple parameterization, computational feasibility, and transparent dose metrics. We further introduce a structure-guided in/out strategy as an optional refinement that restricts mapping probabilities to anatomically plausible target regions. The approach is demonstrated on a prostate radiotherapy case study and used to compare different certainty-map strategies and probability kernels. The experiments show that the certainty-map design has a stronger effect on resulting dose and DVH uncertainty bounds than the specific kernel choice, while the additional benefit of the in/out strategy is case-dependent and modest in the present example. Overall, the proposed framework provides a transparent way to incorporate DIR uncertainty into radiotherapy dose assessment and to study how modelling choices affect propagated dose metrics.
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.
Deformable image registration (DIR) is a core problem in medical image analysis; but, unlike labeling decision problems such as classification and segmentation, registration is a problem class that involves stringent physical constraints. Although deep learning methods have made faster registration possible, the resulting models are often difficult to interpret compared to hand-crafted methods with explicit objectives and interpretable physical meaning. In this work, we show that an analytical method can still yield competitive and superior results to deep learning in a common deformable registration task. We study pTVreg as a parametric total variation based registration in that context. Observing its different implementations to perform at various degrees, we introduce here an accessible implementation of this method, together with a Bayesian optimization framework that automatically sets self-parameters for any DIR task from a set of sample examples. Experiments on Lung250M-4B show that our proposed implementation achieves state-of-the-art results in this benchmark, substantially superior to existing deep learning solutions and other pTVreg variants as baselines. The source code will be made publicly available at https://github.com/oazeybekoglu/ptvreg-python .
We propose a new probabilistic model for general-purpose medical image registration that builds upon the mutual information registration criterion. It centers around a spatial interpolation technique that assumes latent voxel-wise correspondences between the images being registered. By exploiting these latent variables, we derive dedicated optimization and MCMC sampling techniques that only involve closed-form iterative updates. When applied to nonlinear registration, an efficient demons-like optimization algorithm is obtained that shows robust out-of-the-box performance across a variety of monomodal and multimodal registration tasks. We also demonstrate a corresponding sampler that can quantify, for the first time, uncertainty in multimodal registration scenarios with very high-dimensional 3D deformations. Our code, which we call BINDER (Bayesian INference for DEformable Registration), is freely available at https://github.com/ste93ste/BINDER.