Personalising Deformable Image Registration with Clinical Context and Deformation History for Adaptive Radiotherapy

Proton therapy offers superior organ-at-risk sparing but is highly sensitive to anatomical changes, making accurate deformable image registration (DIR) across longitudinal CT scans essential. Conventional DIR methods are often too slow for emerging online adaptive workflows, while existing deep learning-based approaches are primarily designed for generic benchmarks and underutilize clinically relevant information beyond images. To address this gap, we propose a clinically scalable coarse-to-fine deformable registration framework that integrates multimodal information from the proton radiotherapy workflow to accommodate diverse clinical scenarios. The model employs dual CNN-based encoders for hierarchical feature extraction and a transformer-based decoder to progressively refine deformation fields. Beyond CT intensities, clinically critical priors, including target and organ-at-risk contours, dose distributions, and treatment planning text, are incorporated through anatomy- and risk-guided attention, text-conditioned feature modulation, and foreground-aware optimization, enabling anatomically focused and clinically informed deformation estimation. We evaluate the proposed framework on a large-scale proton therapy DIR dataset comprising 1,222 paired planning and repeat CT scans across multiple anatomical regions and disease types. Extensive experiments demonstrate consistent improvements over state-of-the-art methods, enabling fast and robust clinically meaningful registration.

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.

Dose accumulation is increasingly important in adaptive radiation therapy and reirradiation, but its clinical validity depends on the performance of deformable image registration (DIR). Reirradiation of brain metastases (BMs) with stereotactic radiosurgery (SRS) provides a controlled but clinically meaningful DIR test case: intra-subject brain deformation is usually limited after rigid alignment, yet recurrent lesions can undergo substantial local shape and volume changes that rigid registration cannot capture and can affect dose accumulation. We benchmarked a wide range of learning-based and optimization-based DIR methods on 87 manually screened longitudinal contrast-enhanced T1-weighted MRI lesion pairs from an institutional BM SRS retreatment cohort. Learning-based methods pretrained on healthy-brain MRI were evaluated zero-shot and after instance-specific optimization (ISO) or tumor-proximity target-specific optimization (TSO). Registration was assessed using lesion overlap (Dice), surface distance metrics (HD95 and sASD), target-volume recovery, and runtime and memory. Pretrained learning-based methods showed variable zero-shot performance, while ISO/TSO improved all tested learning-based families. However, optimization-based methods remained the best-performing approach while maintaining reasonable runtime. These findings suggest that even state-of-the-art DIR methods do not yet provide sufficiently accurate and consistent registration for unmonitored use in brain metastasis reirradiation dose accumulation. Because accurate registration is a prerequisite for deformable dose accumulation, clinical application will require case-level quality control and direct assessment of how registration uncertainty affects downstream dose metrics.