Foundation models, pre-trained on large image datasets and capable of capturing rich feature representations, have recently shown potential for zero-shot image registration. However, their performance has mostly been tested in the context of rigid or less complex structures, such as the brain or abdominal organs, and it remains unclear whether these models can handle more challenging, deformable anatomy. Breast MRI registration is particularly difficult due to significant anatomical variation between patients, deformation caused by patient positioning, and the presence of thin and complex internal structure of fibroglandular tissue, where accurate alignment is crucial. Whether foundation model-based registration algorithms can address this level of complexity remains an open question. In this study, we provide a comprehensive evaluation of foundation model-based registration algorithms for breast MRI. We assess five pre-trained encoders, including DINO-v2, SAM, MedSAM, SSLSAM, and MedCLIP, across four key breast registration tasks that capture variations in different years and dates, sequences, modalities, and patient disease status (lesion versus no lesion). Our results show that foundation model-based algorithms such as SAM outperform traditional registration baselines for overall breast alignment, especially under large domain shifts, but struggle with capturing fine details of fibroglandular tissue. Interestingly, additional pre-training or fine-tuning on medical or breast-specific images in MedSAM and SSLSAM, does not improve registration performance and may even decrease it in some cases. Further work is needed to understand how domain-specific training influences registration and to explore targeted strategies that improve both global alignment and fine structure accuracy. We also publicly release our code at \href{https://github.com/mazurowski-lab/Foundation-based-reg}{Github}.
Effective representation of Regions of Interest (ROI) and independent alignment of these ROIs can significantly enhance the performance of deformable medical image registration (DMIR). However, current learning-based DMIR methods have limitations. Unsupervised techniques disregard ROI representation and proceed directly with aligning pairs of images, while weakly-supervised methods heavily depend on label constraints to facilitate registration. To address these issues, we introduce a novel ROI-based registration approach named EASR-DCN. Our method represents medical images through effective ROIs and achieves independent alignment of these ROIs without requiring labels. Specifically, we first used a Gaussian mixture model for intensity analysis to represent images using multiple effective ROIs with distinct intensities. Furthermore, we propose a novel Divide-and-Conquer Network (DCN) to process these ROIs through separate channels to learn feature alignments for each ROI. The resultant correspondences are seamlessly integrated to generate a comprehensive displacement vector field. Extensive experiments were performed on three MRI and one CT datasets to showcase the superior accuracy and deformation reduction efficacy of our EASR-DCN. Compared to VoxelMorph, our EASR-DCN achieved improvements of 10.31\% in the Dice score for brain MRI, 13.01\% for cardiac MRI, and 5.75\% for hippocampus MRI, highlighting its promising potential for clinical applications. The code for this work will be released upon acceptance of the paper.
Deformable medical image registration is an essential task in computer-assisted interventions. This problem is particularly relevant to oncological treatments, where precise image alignment is necessary for tracking tumor growth, assessing treatment response, and ensuring accurate delivery of therapies. Recent AI methods can outperform traditional techniques in accuracy and speed, yet they often produce unreliable deformations that limit their clinical adoption. In this work, we address this challenge and introduce a novel implicit registration framework that can predict accurate and reliable deformations. Our insight is to reformulate image registration as a signal reconstruction problem: we learn a kernel function that can recover the dense displacement field from sparse keypoint correspondences. We integrate our method in a novel hierarchical architecture, and estimate the displacement field in a coarse-to-fine manner. Our formulation also allows for efficient refinement at test time, permitting clinicians to easily adjust registrations when needed. We validate our method on challenging intra-patient thoracic and abdominal zero-shot registration tasks, using public and internal datasets from the local University Hospital. Our method not only shows competitive accuracy to state-of-the-art approaches, but also bridges the generalization gap between implicit and explicit registration techniques. In particular, our method generates deformations that better preserve anatomical relationships and matches the performance of specialized commercial systems, underscoring its potential for clinical adoption.
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.
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.
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.
Medical image registration plays a vital role in medical image processing. Extracting expressive representations for medical images is crucial for improving the registration quality. One common practice for this end is constructing a convolutional backbone to enable interactions with skip connections among feature extraction layers. The de facto structure, U-Net-like networks, has attempted to design skip connections such as nested or full-scale ones to connect one single encoder and one single decoder to improve its representation capacity. Despite being effective, it still does not fully explore interactions with a single encoder and decoder architectures. In this paper, we embrace this observation and introduce a simple yet effective alternative strategy to enhance the representations for registrations by appending one additional decoder. The new decoder is designed to interact with both the original encoder and decoder. In this way, it not only reuses feature presentation from corresponding layers in the encoder but also interacts with the original decoder to corporately give more accurate registration results. The new architecture is concise yet generalized, with only one encoder and two decoders forming a ``Tetrahedron'' structure, thereby dubbed Tetrahedron-Net. Three instantiations of Tetrahedron-Net are further constructed regarding the different structures of the appended decoder. Our extensive experiments prove that superior performance can be obtained on several representative benchmarks of medical image registration. Finally, such a ``Tetrahedron'' design can also be easily integrated into popular U-Net-like architectures including VoxelMorph, ViT-V-Net, and TransMorph, leading to consistent performance gains.
In modern cancer research, the vast volume of medical data generated is often underutilised due to challenges related to patient privacy. The OncoReg Challenge addresses this issue by enabling researchers to develop and validate image registration methods through a two-phase framework that ensures patient privacy while fostering the development of more generalisable AI models. Phase one involves working with a publicly available dataset, while phase two focuses on training models on a private dataset within secure hospital networks. OncoReg builds upon the foundation established by the Learn2Reg Challenge by incorporating the registration of interventional cone-beam computed tomography (CBCT) with standard planning fan-beam CT (FBCT) images in radiotherapy. Accurate image registration is crucial in oncology, particularly for dynamic treatment adjustments in image-guided radiotherapy, where precise alignment is necessary to minimise radiation exposure to healthy tissues while effectively targeting tumours. This work details the methodology and data behind the OncoReg Challenge and provides a comprehensive analysis of the competition entries and results. Findings reveal that feature extraction plays a pivotal role in this registration task. A new method emerging from this challenge demonstrated its versatility, while established approaches continue to perform comparably to newer techniques. Both deep learning and classical approaches still play significant roles in image registration, with the combination of methods - particularly in feature extraction - proving most effective.
Image registration is fundamental in medical imaging, enabling precise alignment of anatomical structures for diagnosis, treatment planning, image-guided interventions, and longitudinal monitoring. This work introduces IMPACT (Image Metric with Pretrained model-Agnostic Comparison for Transmodality registration), a novel similarity metric designed for robust multimodal image registration. Rather than relying on raw intensities, handcrafted descriptors, or task-specific training, IMPACT defines a semantic similarity measure based on the comparison of deep features extracted from large-scale pretrained segmentation models. By leveraging representations from models such as TotalSegmentator, Segment Anything (SAM), and other foundation networks, IMPACT provides a task-agnostic, training-free solution that generalizes across imaging modalities. These features, originally trained for segmentation, offer strong spatial correspondence and semantic alignment capabilities, making them naturally suited for registration. The method integrates seamlessly into both algorithmic (Elastix) and learning-based (VoxelMorph) frameworks, leveraging the strengths of each. IMPACT was evaluated on five challenging 3D registration tasks involving thoracic CT/CBCT and pelvic MR/CT datasets. Quantitative metrics, including Target Registration Error and Dice Similarity Coefficient, demonstrated consistent improvements in anatomical alignment over baseline methods. Qualitative analyses further highlighted the robustness of the proposed metric in the presence of noise, artifacts, and modality variations. With its versatility, efficiency, and strong performance across diverse tasks, IMPACT offers a powerful solution for advancing multimodal image registration in both clinical and research settings.
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 .
Deformable image registration is a fundamental task in medical image processing. Traditional optimization-based methods often struggle with accuracy in dealing with complex deformation. Recently, learning-based methods have achieved good performance on public datasets, but the scarcity of medical image data makes it challenging to build a generalizable model to handle diverse real-world scenarios. To address this, we propose a training-data-free learning-based method, Neural Correspondence Field (NCF), which can learn from just one data pair. Our approach employs a compact neural network to model the correspondence field and optimize model parameters for each individual image pair. Consequently, each pair has a unique set of network weights. Notably, our model is highly efficient, utilizing only 0.06 million parameters. Evaluation results showed that the proposed method achieved superior performance on a public Lung CT dataset and outperformed a traditional method on a head and neck dataset, demonstrating both its effectiveness and efficiency.
Vision foundation models (VFMs) are pre-trained on extensive image datasets to learn general representations for diverse types of data. These models can subsequently be fine-tuned for specific downstream tasks, significantly boosting performance across a broad range of applications. However, existing vision foundation models that claim to be applicable to various radiology tasks are mostly pre-trained on 3D computed tomography (CT), which benefits from the availability of extensive 3D CT databases. Significant differences between CT and magnetic resonance imaging (MRI) in imaging principles, signal characteristics, and data distribution may hinder their practical performance and versatility in MRI-specific applications. Here, we propose Triad, a vision foundation model for 3D MRI. Triad adopts a widely used autoencoder architecture to learn robust representations from 131,170 3D MRI volumes and uses organ-independent imaging descriptions to constrain the semantic distribution of the visual modality. The above pre-training dataset is called Triad-131K, which is currently the largest 3D MRI pre-training dataset. We evaluate Triad across three tasks, namely, organ/tumor segmentation, organ/cancer classification, and medical image registration, in two data modalities (within-domain and out-of-domain) settings using 25 downstream datasets. By initializing models with Triad's pre-trained weights, nnUNet-Triad improves segmentation performance by 6.88% compared to nnUNet-Scratch across 17 datasets. Swin-B-Triad achieves a 3.97% improvement over Swin-B-Scratch in classification tasks across five datasets. SwinUNETR-Triad improves by 4.00% compared to SwinUNETR-Scratch in registration tasks across two datasets. Our study demonstrates that pre-training can maximize performance when the data modalities and organs of upstream and downstream tasks are consistent.
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.
Deformable image registration is a fundamental requirement for medical image analysis. Recently, transformers have been widely used in deep learning-based registration methods for their ability to capture long-range dependency via self-attention (SA). However, the high computation and memory loads of SA (growing quadratically with the spatial resolution) hinder transformers from processing subtle textural information in high-resolution image features, e.g., at the full and half image resolutions. This limits deformable registration as the high-resolution textural information is crucial for finding precise pixel-wise correspondence between subtle anatomical structures. Cross-covariance Attention (XCA), as a "transposed" version of SA that operates across feature channels, has complexity growing linearly with the spatial resolution, providing the feasibility of capturing long-range dependency among high-resolution image features. However, existing XCA-based transformers merely capture coarse global long-range dependency, which are unsuitable for deformable image registration relying primarily on fine-grained local correspondence. In this study, we propose to improve existing deep learning-based registration methods by embedding a new XCA mechanism. To this end, we design an XCA-based transformer block optimized for deformable medical image registration, named Multi-Axis XCA (MAXCA). Our MAXCA serves as a general network block that can be embedded into various registration network architectures. It can capture both global and local long-range dependency among high-resolution image features by applying regional and dilated XCA in parallel via a multi-axis design. Extensive experiments on two well-benchmarked inter-/intra-patient registration tasks with seven public medical datasets demonstrate that our MAXCA block enables state-of-the-art registration performance.
Image registration is fundamental in medical imaging applications, such as disease progression analysis or radiation therapy planning. The primary objective of image registration is to precisely capture the deformation between two or more images, typically achieved by minimizing an optimization problem. Due to its inherent ill-posedness, regularization is a key component in driving the solution toward anatomically meaningful deformations. A wide range of regularization methods has been proposed for both conventional and deep learning-based registration. However, the appropriate application of regularization techniques often depends on the specific registration problem, and no one-fits-all method exists. Despite its importance, regularization is often overlooked or addressed with default approaches, assuming existing methods are sufficient. A comprehensive and structured review remains missing. This review addresses this gap by introducing a novel taxonomy that systematically categorizes the diverse range of proposed regularization methods. It highlights the emerging field of learned regularization, which leverages data-driven techniques to automatically derive deformation properties from the data. Moreover, this review examines the transfer of regularization methods from conventional to learning-based registration, identifies open challenges, and outlines future research directions. By emphasizing the critical role of regularization in image registration, we hope to inspire the research community to reconsider regularization strategies in modern registration algorithms and to explore this rapidly evolving field further.
Deformable image registration plays an essential role in various medical image tasks. Existing deep learning-based deformable registration frameworks primarily utilize convolutional neural networks (CNNs) or Transformers to learn features to predict the deformations. However, the lack of semantic information in the learned features limits the registration performance. Furthermore, the similarity metric of the loss function is often evaluated only in the pixel space, which ignores the matching of high-level anatomical features and can lead to deformation folding. To address these issues, in this work, we proposed LDM-Morph, an unsupervised deformable registration algorithm for medical image registration. LDM-Morph integrated features extracted from the latent diffusion model (LDM) to enrich the semantic information. Additionally, a latent and global feature-based cross-attention module (LGCA) was designed to enhance the interaction of semantic information from LDM and global information from multi-head self-attention operations. Finally, a hierarchical metric was proposed to evaluate the similarity of image pairs in both the original pixel space and latent-feature space, enhancing topology preservation while improving registration accuracy. Extensive experiments on four public 2D cardiac image datasets show that the proposed LDM-Morph framework outperformed existing state-of-the-art CNNs- and Transformers-based registration methods regarding accuracy and topology preservation with comparable computational efficiency. Our code is publicly available at https://github.com/wujiong-hub/LDM-Morph.
Diffeomorphic image registration is crucial for various medical imaging applications because it can preserve the topology of the transformation. This study introduces DCCNN-LSTM-Reg, a learning framework that evolves dynamically and learns a symmetrical registration path by satisfying a specified control increment system. This framework aims to obtain symmetric diffeomorphic deformations between moving and fixed images. To achieve this, we combine deep learning networks with diffeomorphic mathematical mechanisms to create a continuous and dynamic registration architecture, which consists of multiple Symmetric Registration (SR) modules cascaded on five different scales. Specifically, our method first uses two U-nets with shared parameters to extract multiscale feature pyramids from the images. We then develop an SR-module comprising a sequential CNN-LSTM architecture to progressively correct the forward and reverse multiscale deformation fields using control increment learning and the homotopy continuation technique. Through extensive experiments on three 3D registration tasks, we demonstrate that our method outperforms existing approaches in both quantitative and qualitative evaluations.
Medical image registration is a critical process that aligns various patient scans, facilitating tasks like diagnosis, surgical planning, and tracking. Traditional optimization based methods are slow, prompting the use of Deep Learning (DL) techniques, such as VoxelMorph and Transformer-based strategies, for faster results. However, these DL methods often impose significant resource demands. In response to these challenges, we present NCA-Morph, an innovative approach that seamlessly blends DL with a bio-inspired communication and networking approach, enabled by Neural Cellular Automata (NCAs). NCA-Morph not only harnesses the power of DL for efficient image registration but also builds a network of local communications between cells and respective voxels over time, mimicking the interaction observed in living systems. In our extensive experiments, we subject NCA-Morph to evaluations across three distinct 3D registration tasks, encompassing Brain, Prostate and Hippocampus images from both healthy and diseased patients. The results showcase NCA-Morph's ability to achieve state-of-the-art performance. Notably, NCA-Morph distinguishes itself as a lightweight architecture with significantly fewer parameters; 60% and 99.7% less than VoxelMorph and TransMorph. This characteristic positions NCA-Morph as an ideal solution for resource-constrained medical applications, such as primary care settings and operating rooms.
Complicated image registration is a key issue in medical image analysis, and deep learning-based methods have achieved better results than traditional methods. The methods include ConvNet-based and Transformer-based methods. Although ConvNets can effectively utilize local information to reduce redundancy via small neighborhood convolution, the limited receptive field results in the inability to capture global dependencies. Transformers can establish long-distance dependencies via a self-attention mechanism; however, the intense calculation of the relationships among all tokens leads to high redundancy. We propose a novel unsupervised image registration method named the unified Transformer and superresolution (UTSRMorph) network, which can enhance feature representation learning in the encoder and generate detailed displacement fields in the decoder to overcome these problems. We first propose a fusion attention block to integrate the advantages of ConvNets and Transformers, which inserts a ConvNet-based channel attention module into a multihead self-attention module. The overlapping attention block, a novel cross-attention method, uses overlapping windows to obtain abundant correlations with match information of a pair of images. Then, the blocks are flexibly stacked into a new powerful encoder. The decoder generation process of a high-resolution deformation displacement field from low-resolution features is considered as a superresolution process. Specifically, the superresolution module was employed to replace interpolation upsampling, which can overcome feature degradation. UTSRMorph was compared to state-of-the-art registration methods in the 3D brain MR (OASIS, IXI) and MR-CT datasets. The qualitative and quantitative results indicate that UTSRMorph achieves relatively better performance. The code and datasets are publicly available at https://github.com/Runshi-Zhang/UTSRMorph.
Currently, cortical surface registration techniques based on classical methods have been well developed. However, a key issue with classical methods is that for each pair of images to be registered, it is necessary to search for the optimal transformation in the deformation space according to a specific optimization algorithm until the similarity measure function converges, which cannot meet the requirements of real-time and high-precision in medical image registration. Researching cortical surface registration based on deep learning models has become a new direction. But so far, there are still only a few studies on cortical surface image registration based on deep learning. Moreover, although deep learning methods theoretically have stronger representation capabilities, surpassing the most advanced classical methods in registration accuracy and distortion control remains a challenge. Therefore, to address this challenge, this paper constructs a deep learning model to study the technology of cortical surface image registration. The specific work is as follows: (1) An unsupervised cortical surface registration network based on a multi-scale cascaded structure is designed, and a convolution method based on spherical harmonic transformation is introduced to register cortical surface data. This solves the problem of scale-inflexibility of spherical feature transformation and optimizes the multi-scale registration process. (2)By integrating the attention mechanism, a graph-enhenced module is introduced into the registration network, using the graph attention module to help the network learn global features of cortical surface data, enhancing the learning ability of the network. The results show that the graph attention module effectively enhances the network's ability to extract global features, and its registration results have significant advantages over other methods.