Benchmarking Intra-Patient 3D Deformable Multimodal Image Registration
Authors: Matteo Barbieri, Giammarco La Barbera, Juan Pablo De La Plata, Sabine Sarnacki, Isabelle Bloch, Pietro Gori
Abstract
Multimodal image registration is a key component of many clinical workflows, yet it remains challenging because corresponding anatomical structures often exhibit substantially different image intensities across modalities. In this work, we present a comprehensive benchmark of intra-patient 3D multimodal deformable registration methods across three datasets covering different anatomical regions and difficulty levels, including both synthetic deformation recovery and real clinical scenarios. We evaluate classical optimization-based approaches and modern learning-based methods, including recent deep learning and foundation models, using complementary metrics: Average Dice similarity coefficient (DSC), average 95th-percentile Hausdorff distance (HD95), and a modality-independent structural similarity measure based on the MIND self-similarity context (MIND-SSC). Results show high variability across datasets, with learning-based methods demonstrating superior performance on large synthetic benchmarks, while only limited improvements are observed in real pelvic registration. A key finding of this study is the consistent disagreement between geometric metrics (DSC, HD95) and image-based similarity metrics (MIND-SSC), highlighting that improved overlap does not necessarily imply better global multimodal correspondence. Furthermore, anatomy-guided approaches achieve the highest overlap scores but exhibit degraded performance outside of segmented regions, revealing a trade-off between label-driven alignment and global structural coherence. Overall, our results indicate that no current method achieves robust performance across anatomies and modalities. We demonstrate that intra-patient 3D multimodal registration requires multi-criteria evaluation, including deformation-based metrics, and remains an open problem.
Intraoperative 2D/3D registration aligns preoperative CT volumes with intraoperative X-ray or fluoroscopic images and is essential for image-guided interventions. Recent learning-based and differentiable registration methods have shown promising accuracy, especially in patient-specific settings where abundant digitally reconstructed radiographs (DRRs) can be synthesized from the target CT. However, training a separate patient-specific model from scratch for every new patient is computationally inefficient and limits practical deployment. In this work, we propose an efficient patient-specific 2D/3D registration framework based on patient-agnostic synthetic pretraining and spherical similarity learning. The model is first pretrained on synthetic DRRs generated from multiple CT volumes to learn transferable pose-sensitive representations, and is then adapted to a new patient using only a limited number of synthetic projections from the target CT. To improve synthetic-to-real robustness without requiring anatomical labels, we introduce a segmentation-free domain randomization strategy that perturbs image intensity, projection physics, field-of-view, occlusion, and fluoroscopic artifacts. The adapted model provides an initial pose estimate, which is further refined using spherical similarity learning and differentiable Levenberg-Marquardt optimization. Experiments on multiple anatomical datasets evaluate whether patient-agnostic synthetic pretraining can improve the efficiency of patient-specific registration, with particular focus on the trade-off between adaptation cost and registration accuracy. The results demonstrate that patient-agnostic synthetic pretraining can significantly reduce patient-specific training requirements while preserving accurate intraoperative 2D/3D registration.
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.
Learning-based medical image registration has matched the accuracy of conventional methods while offering superior computational efficiency. However, existing approaches suffer from poor generalization across diverse clinical scenarios, requiring the laborious development of multiple isolated networks for specific registration tasks, \emph{e.g.}, inter-/intra-subject registration or anatomical region-specific alignment, leading to cumbersome development pipelines. To overcome this limitation, we propose \textbf{UniReg}, the first conditional unified model for multi-scenario medical image registration, which combines the precision advantages of task-specific learning methods with the generalization of traditional optimization methods. Our key innovation is a unified registration framework that adaptively estimates deformation fields conditioned on: (1) anatomical structure priors, (2) registration type constraints (inter/intra-subject), and (3) instance-specific features, enabling effective alignment across heterogeneous CT and MR registration scenarios within a single model. Through comprehensive experiments on multiple CT/MR registration datasets, UniReg achieves superior average registration accuracy compared with current state-of-the-art learning-based methods while exhibiting strong cross-scenario generalization. Moreover, by replacing multiple isolated task-specific models with a compact unified model, UniReg substantially reduces the overall training burden in terms of total training cost and model redundancy.