Pretraining Deformable Image Registration Networks with Random Images

Recent advances in deep learning-based medical image registration have shown that training deep neural networks~(DNNs) does not necessarily require medical images. Previous work showed that DNNs trained on randomly generated images with carefully designed noise and contrast properties can still generalize well to unseen medical data. Building on this insight, we propose using registration between random images as a proxy task for pretraining a foundation model for image registration. Empirical results show that our pretraining strategy improves registration accuracy, reduces the amount of domain-specific data needed to achieve competitive performance, and accelerates convergence during downstream training, thereby enhancing computational efficiency.

Beyond the LUMIR challenge: The pathway to foundational registration models

Medical image challenges have played a transformative role in advancing the field, catalyzing algorithmic innovation and establishing new performance standards across diverse clinical applications. Image registration, a foundational task in neuroimaging pipelines, has similarly benefited from the Learn2Reg initiative. Building on this foundation, we introduce the Large-scale Unsupervised Brain MRI Image Registration (LUMIR) challenge, a next-generation benchmark designed to assess and advance unsupervised brain MRI registration. Distinct from prior challenges that leveraged anatomical label maps for supervision, LUMIR removes this dependency by providing over 4,000 preprocessed T1-weighted brain MRIs for training without any label maps, encouraging biologically plausible deformation modeling through self-supervision. In addition to evaluating performance on 590 held-out test subjects, LUMIR introduces a rigorous suite of zero-shot generalization tasks, spanning out-of-domain imaging modalities (e.g., FLAIR, T2-weighted, T2*-weighted), disease populations (e.g., Alzheimer's disease), acquisition protocols (e.g., 9.4T MRI), and species (e.g., macaque brains). A total of 1,158 subjects and over 4,000 image pairs were included for evaluation. Performance was assessed using both segmentation-based metrics (Dice coefficient, 95th percentile Hausdorff distance) and landmark-based registration accuracy (target registration error). Across both in-domain and zero-shot tasks, deep learning-based methods consistently achieved state-of-the-art accuracy while producing anatomically plausible deformation fields. The top-performing deep learning-based models demonstrated diffeomorphic properties and inverse consistency, outperforming several leading optimization-based methods, and showing strong robustness to most domain shifts, the exception being a drop in performance on out-of-domain contrasts.

Improving Generalization of Medical Image Registration Foundation Model

Deformable registration is a fundamental task in medical image processing, aiming to achieve precise alignment by establishing nonlinear correspondences between images. Traditional methods offer good adaptability and interpretability but are limited by computational efficiency. Although deep learning approaches have significantly improved registration speed and accuracy, they often lack flexibility and generalizability across different datasets and tasks. In recent years, foundation models have emerged as a promising direction, leveraging large and diverse datasets to learn universal features and transformation patterns for image registration, thus demonstrating strong cross-task transferability. However, these models still face challenges in generalization and robustness when encountering novel anatomical structures, varying imaging conditions, or unseen modalities. To address these limitations, this paper incorporates Sharpness-Aware Minimization (SAM) into foundation models to enhance their generalization and robustness in medical image registration. By optimizing the flatness of the loss landscape, SAM improves model stability across diverse data distributions and strengthens its ability to handle complex clinical scenarios. Experimental results show that foundation models integrated with SAM achieve significant improvements in cross-dataset registration performance, offering new insights for the advancement of medical image registration technology. Our code is available at https://github.com/Promise13/fm_sam}{https://github.com/Promise13/fm\_sam.

FF-PNet: A Pyramid Network Based on Feature and Field for Brain Image Registration

In recent years, deformable medical image registration techniques have made significant progress. However, existing models still lack efficiency in parallel extraction of coarse and fine-grained features. To address this, we construct a new pyramid registration network based on feature and deformation field (FF-PNet). For coarse-grained feature extraction, we design a Residual Feature Fusion Module (RFFM), for fine-grained image deformation, we propose a Residual Deformation Field Fusion Module (RDFFM). Through the parallel operation of these two modules, the model can effectively handle complex image deformations. It is worth emphasizing that the encoding stage of FF-PNet only employs traditional convolutional neural networks without any attention mechanisms or multilayer perceptrons, yet it still achieves remarkable improvements in registration accuracy, fully demonstrating the superior feature decoding capabilities of RFFM and RDFFM. We conducted extensive experiments on the LPBA and OASIS datasets. The results show our network consistently outperforms popular methods in metrics like the Dice Similarity Coefficient.

Biomechanical Constraints Assimilation in Deep-Learning Image Registration: Application to sliding and locally rigid deformations

Regularization strategies in medical image registration often take a one-size-fits-all approach by imposing uniform constraints across the entire image domain. Yet biological structures are anything but regular. Lacking structural awareness, these strategies may fail to consider a panoply of spatially inhomogeneous deformation properties, which would faithfully account for the biomechanics of soft and hard tissues, especially in poorly contrasted structures. To bridge this gap, we propose a learning-based image registration approach in which the inferred deformation properties can locally adapt themselves to trained biomechanical characteristics. Specifically, we first enforce in the training process local rigid displacements, shearing motions or pseudo-elastic deformations using regularization losses inspired from the field of solid-mechanics. We then show on synthetic and real 3D thoracic and abdominal images that these mechanical properties of different nature are well generalized when inferring the deformations between new image pairs. Our approach enables neural-networks to infer tissue-specific deformation patterns directly from input images, ensuring mechanically plausible motion. These networks preserve rigidity within hard tissues while allowing controlled sliding in regions where tissues naturally separate, more faithfully capturing physiological motion. The code is publicly available at https://github.com/Kheil-Z/biomechanical_DLIR .

SACB-Net: Spatial-awareness Convolutions for Medical Image Registration

Deep learning-based image registration methods have shown state-of-the-art performance and rapid inference speeds. Despite these advances, many existing approaches fall short in capturing spatially varying information in non-local regions of feature maps due to the reliance on spatially-shared convolution kernels. This limitation leads to suboptimal estimation of deformation fields. In this paper, we propose a 3D Spatial-Awareness Convolution Block (SACB) to enhance the spatial information within feature representations. Our SACB estimates the spatial clusters within feature maps by leveraging feature similarity and subsequently parameterizes the adaptive convolution kernels across diverse regions. This adaptive mechanism generates the convolution kernels (weights and biases) tailored to spatial variations, thereby enabling the network to effectively capture spatially varying information. Building on SACB, we introduce a pyramid flow estimator (named SACB-Net) that integrates SACBs to facilitate multi-scale flow composition, particularly addressing large deformations. Experimental results on the brain IXI and LPBA datasets as well as Abdomen CT datasets demonstrate the effectiveness of SACB and the superiority of SACB-Net over the state-of-the-art learning-based registration methods. The code is available at https://github.com/x-xc/SACB_Net .

New multimodal similarity measure for image registration via modeling local functional dependence with linear combination of learned basis functions

The deformable registration of images of different modalities, essential in many medical imaging applications, remains challenging. The main challenge is developing a robust measure for image overlap despite the compared images capturing different aspects of the underlying tissue. Here, we explore similarity metrics based on functional dependence between intensity values of registered images. Although functional dependence is too restrictive on the global scale, earlier work has shown competitive performance in deformable registration when such measures are applied over small enough contexts. We confirm this finding and further develop the idea by modeling local functional dependence via the linear basis function model with the basis functions learned jointly with the deformation. The measure can be implemented via convolutions, making it efficient to compute on GPUs. We release the method as an easy-to-use tool and show good performance on three datasets compared to well-established baseline and earlier functional dependence-based methods.

UniReg: Foundation Model for Controllable Medical Image Registration

Learning-based medical image registration has achieved performance parity with conventional methods while demonstrating a substantial advantage in computational efficiency. However, learning-based registration approaches lack generalizability across diverse clinical scenarios, requiring the laborious development of multiple isolated networks for specific registration tasks, e.g., inter-/intra-subject registration or organ-specific alignment. % To overcome this limitation, we propose \textbf{UniReg}, the first interactive foundation model for 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 framework for diverse registration scenarios, achieved through a conditional deformation field estimation within a unified registration model. This is realized through a dynamic learning paradigm that explicitly encodes: (1) anatomical structure priors, (2) registration type constraints (inter/intra-subject), and (3) instance-specific features, enabling the generation of scenario-optimal deformation fields. % Through comprehensive experiments encompassing $90$ anatomical structures at different body regions, our UniReg model demonstrates comparable performance with contemporary state-of-the-art methodologies while achieving ~50\% reduction in required training iterations relative to the conventional learning-based paradigm. This optimization contributes to a significant reduction in computational resources, such as training time. Code and model will be available.

SynthRAD2025 Grand Challenge dataset: generating synthetic CTs for radiotherapy

Medical imaging is essential in modern radiotherapy, supporting diagnosis, treatment planning, and monitoring. Synthetic imaging, particularly synthetic computed tomography (sCT), is gaining traction in radiotherapy. The SynthRAD2025 dataset and Grand Challenge promote advancements in sCT generation by providing a benchmarking platform for algorithms using cone-beam CT (CBCT) and magnetic resonance imaging (MRI). The dataset includes 2362 cases: 890 MRI-CT and 1472 CBCT-CT pairs from head-and-neck, thoracic, and abdominal cancer patients treated at five European university medical centers (UMC Groningen, UMC Utrecht, Radboud UMC, LMU University Hospital Munich, and University Hospital of Cologne). Data were acquired with diverse scanners and protocols. Pre-processing, including rigid and deformable image registration, ensures high-quality, modality-aligned images. Extensive quality assurance validates image consistency and usability. All imaging data is provided in MetaImage (.mha) format, ensuring compatibility with medical image processing tools. Metadata, including acquisition parameters and registration details, is available in structured CSV files. To maintain dataset integrity, SynthRAD2025 is divided into training (65%), validation (10%), and test (25%) sets. The dataset is accessible at https://doi.org/10.5281/zenodo.14918089 under the SynthRAD2025 collection. This dataset supports benchmarking and the development of synthetic imaging techniques for radiotherapy applications. Use cases include sCT generation for MRI-only and MR-guided photon/proton therapy, CBCT-based dose calculations, and adaptive radiotherapy workflows. By integrating diverse acquisition settings, SynthRAD2025 fosters robust, generalizable image synthesis algorithms, advancing personalized cancer care and adaptive radiotherapy.

Medical Image Registration Meets Vision Foundation Model: Prototype Learning and Contour Awareness

Medical image registration is a fundamental task in medical image analysis, aiming to establish spatial correspondences between paired images. However, existing unsupervised deformable registration methods rely solely on intensity-based similarity metrics, lacking explicit anatomical knowledge, which limits their accuracy and robustness. Vision foundation models, such as the Segment Anything Model (SAM), can generate high-quality segmentation masks that provide explicit anatomical structure knowledge, addressing the limitations of traditional methods that depend only on intensity similarity. Based on this, we propose a novel SAM-assisted registration framework incorporating prototype learning and contour awareness. The framework includes: (1) Explicit anatomical information injection, where SAM-generated segmentation masks are used as auxiliary inputs throughout training and testing to ensure the consistency of anatomical information; (2) Prototype learning, which leverages segmentation masks to extract prototype features and aligns prototypes to optimize semantic correspondences between images; and (3) Contour-aware loss, a contour-aware loss is designed that leverages the edges of segmentation masks to improve the model's performance in fine-grained deformation fields. Extensive experiments demonstrate that the proposed framework significantly outperforms existing methods across multiple datasets, particularly in challenging scenarios with complex anatomical structures and ambiguous boundaries. Our code is available at https://github.com/HaoXu0507/IPMI25-SAM-Assisted-Registration.