The Right Prior for the Right Deformation: Rethinking Continuous Deformable Image Registration

Deformable image registration models implicitly encode deformation priors through their parametrization and optimization. In this work, we conduct a validation study on continuous registration methods to examine how these implicit priors affect performance across different registration tasks. Classic B-Spline transformations impose locality, smoothness, and scale through their control-point structure, whereas recent INR-based methods impose different priors through neural parameterization and optimization. We compare INR-Dense (IDIR), which directly models a dense displacement field using a SIREN-based INR; INR-BSCP (SINR), which predicts B-Spline control points with an INR; D-BSCP, which directly optimizes single-scale B-Spline control points; and MR-D-BSCP, which adds a multiresolution coarse-to-fine scheme. Experiments on inter-subject brain MR registration (OASIS) and intra-subject exhale-to-inhale lung CT registration (DIR-LAB 4DCT) reveal different behavior across deformation regimes. On OASIS, where deformations are moderate but locally complex, D-BSCP matches or slightly outperforms INR-BSCP, suggesting that the B-Spline parameterization accounts for much of INR-BSCP's effectiveness. On DIR-LAB 4DCT, where respiratory motion is larger and more coherent, single-scale B-Spline methods (D-BSCP and INR-BSCP) are less suitable, while INR-Dense and MR-D-BSCP are more effective. Across both tasks, MR-D-BSCP achieves the best performance among the tested continuous parameterizations. These findings highlight that registration accuracy depends strongly on matching the induced deformation prior to the target motion pattern, and support prior-deformation matching as a practical design principle for medical image registration. Our code will be available at https://github.com/HengjieLiu/RightPriorDIR.

Anticipatory Digital Twins for Online Head-and-Neck Adaptive Proton Therapy via Foundation-Model Registration

Head-and-neck (HN) proton therapy is highly sensitive to anatomical change over a 4-to-6-week course, as tumor shrinkage, weight loss, and setup variation can misposition the Bragg peak near critical organs such as the parotids, oral cavity, brainstem, and spinal cord, leading to target underdosing or organ-at-risk overdosing. Online adaptive proton therapy replans on the anatomy of the day, yet standard workflows rely on offline replanning that requires repeated CT acquisition and roughly a week of preparation, adding burden, cost, and delay. We investigate whether a patient's treatment-day anatomy can be predicted before image acquisition by transferring longitudinal change from a population database. We propose a digital-twin framework built on a pretrained foundation-model deformable registration network used without patient-specific training. A first registration aligns a prior patient's planning CT to the target and carries the prior's during-treatment quality assurance CT (QACT) into the target frame; a second registration estimates the prior's planning-to-QACT change, which is then applied to the target's own planning CT to synthesize predicted CTs (pdCTs) with propagated contours. Using 88 HN patients, each with a planning CT and three QACTs, we show that pdCTs better match treatment-day anatomy than the static planning CT. Compared with the planning CT alone, normalized cross-correlation improves by 22.8%, Dice for organs-at-risk by 20.2%, and CT-number error decreases by 23.4%. Gains are largest for patients with major anatomical change and negligible when anatomy is stable. This cross-patient motion transfer leverages the digital-twin concept to anticipate treatment-day anatomy, enabling personalized online adaptive proton therapy without repeated imaging.

Contour-Constrained Deformable Registration with Parameter Characterization for Head and Neck Surgical Guidance

With 890,000 annual new cases globally, head and neck squamous cell carcinoma has one of the highest recurrence rates among solid malignancies. Although frozen section analysis is the standard of care for intraoperative margin assessment, accurately relocating detected positive margins on the resection bed remains challenging due to imprecise alignment between resected specimens and their resection bed, compounded by post-resection mucosal tissue shrinkage. We present a biomechanics-driven deformable registration framework that corrects post-resection tissue deformation to provide intraoperative guidance. Our approach registers 3D specimen meshes to intraoperative resection bed point clouds using a deformable registration approach based on regularized Kelvinlet basis functions. The registration matches surface point clouds, fiducial landmarks, and boundary contour constraints that directly penalize perpendicular distance-to-agreement between specimen and resection bed boundaries. Across nine specimens from skin, buccal mucosa, and tongue sites, the overall mean target registration error was $11.11 \pm 4.07$ mm using rigid registration, which decreased to $8.20 \pm 2.68$ mm (26.19\% reduction) using deformable registration without contour constraint. The proposed contour-constrained deformable registration further reduced the error to $5.62 \pm 2.28$ mm, a 49.41\% reduction relative to rigid registration. We observed the largest reduction in the most clinically challenging tongue specimens. We also performed a systematic two-stage parameter search to characterize the relative importance of surface alignment, fiducial correspondences, contour constraint, and strain energy regularization. This search revealed that contour weighting dominates registration accuracy for tissue types with large lateral deformation, while the algorithm operates over a broad range of parameter combinations.