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.
Spatial transformations that capture population-level morphological statistics are critical for medical image analysis. Commonly used smoothness regularizers for image registration fail to integrate population statistics, leading to anatomically inconsistent transformations. Inverse consistency regularizers promote geometric consistency but lack population morphometrics integration. Regularizers that constrain deformation to low-dimensional manifold methods address this. However, they prioritize reconstruction over interpretability and neglect diffeomorphic properties, such as group composition and inverse consistency. We introduce MORPH-LER, a Log-Euclidean regularization framework for population-aware unsupervised image registration. MORPH-LER learns population morphometrics from spatial transformations to guide and regularize registration networks, ensuring anatomically plausible deformations. It features a bottleneck autoencoder that computes the principal logarithm of deformation fields via iterative square-root predictions. It creates a linearized latent space that respects diffeomorphic properties and enforces inverse consistency. By integrating a registration network with a diffeomorphic autoencoder, MORPH-LER produces smooth, meaningful deformation fields. The framework offers two main contributions: (1) a data-driven regularization strategy that incorporates population-level anatomical statistics to enhance transformation validity and (2) a linearized latent space that enables compact and interpretable deformation fields for efficient population morphometrics analysis. We validate MORPH-LER across two families of deep learning-based registration networks, demonstrating its ability to produce anatomically accurate, computationally efficient, and statistically meaningful transformations on the OASIS-1 brain imaging dataset.
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.
U-Net style networks are commonly utilized in unsupervised image registration to predict dense displacement fields, which for high-resolution volumetric image data is a resource-intensive and time-consuming task. To tackle this challenge, we first propose Fourier-Net, which replaces the costly U-Net style expansive path with a parameter-free model-driven decoder. Instead of directly predicting a full-resolution displacement field, our Fourier-Net learns a low-dimensional representation of the displacement field in the band-limited Fourier domain which our model-driven decoder converts to a full-resolution displacement field in the spatial domain. Expanding upon Fourier-Net, we then introduce Fourier-Net+, which additionally takes the band-limited spatial representation of the images as input and further reduces the number of convolutional layers in the U-Net style network's contracting path. Finally, to enhance the registration performance, we propose a cascaded version of Fourier-Net+. We evaluate our proposed methods on three datasets, on which our proposed Fourier-Net and its variants achieve comparable results with current state-of-the art methods, while exhibiting faster inference speeds, lower memory footprint, and fewer multiply-add operations. With such small computational cost, our Fourier-Net+ enables the efficient training of large-scale 3D registration on low-VRAM GPUs. Our code is publicly available at \url{https://github.com/xi-jia/Fourier-Net}.
The Swin transformer has recently attracted attention in medical image analysis due to its computational efficiency and long-range modeling capability. Owing to these properties, the Swin Transformer is suitable for establishing more distant relationships between corresponding voxels in different positions in complex abdominal image registration tasks. However, the registration models based on transformers combine multiple voxels into a single semantic token. This merging process limits the transformers to model and generate coarse-grained spatial information. To address this issue, we propose Recovery Feature Resolution Network (RFRNet), which allows the transformer to contribute fine-grained spatial information and rich semantic correspondences to higher resolution levels. Furthermore, shifted window partitioning operations are inflexible, indicating that they cannot perceive the semantic information over uncertain distances and automatically bridge the global connections between windows. Therefore, we present a Weighted Window Attention (WWA) to build global interactions between windows automatically. It is implemented after the regular and cyclic shift window partitioning operations within the Swin transformer block. The proposed unsupervised deformable image registration model, named RFR-WWANet, detects the long-range correlations, and facilitates meaningful semantic relevance of anatomical structures. Qualitative and quantitative results show that RFR-WWANet achieves significant improvements over the current state-of-the-art methods. Ablation experiments demonstrate the effectiveness of the RFRNet and WWA designs. Our code is available at \url{https://github.com/MingR-Ma/RFR-WWANet}.
Unsupervised image registration commonly adopts U-Net style networks to predict dense displacement fields in the full-resolution spatial domain. For high-resolution volumetric image data, this process is however resource-intensive and time-consuming. To tackle this problem, we propose the Fourier-Net, replacing the expansive path in a U-Net style network with a parameter-free model-driven decoder. Specifically, instead of our Fourier-Net learning to output a full-resolution displacement field in the spatial domain, we learn its low-dimensional representation in a band-limited Fourier domain. This representation is then decoded by our devised model-driven decoder (consisting of a zero padding layer and an inverse discrete Fourier transform layer) to the dense, full-resolution displacement field in the spatial domain. These changes allow our unsupervised Fourier-Net to contain fewer parameters and computational operations, resulting in faster inference speeds. Fourier-Net is then evaluated on two public 3D brain datasets against various state-of-the-art approaches. For example, when compared to a recent transformer-based method, named TransMorph, our Fourier-Net, which only uses 2.2\% of its parameters and 6.66\% of the multiply-add operations, achieves a 0.5\% higher Dice score and an 11.48 times faster inference speed. Code is available at \url{https://github.com/xi-jia/Fourier-Net}.
Medical image registration is a fundamental and critical task in medical image analysis. With the rapid development of deep learning, convolutional neural networks (CNN) have dominated the medical image registration field. Due to the disadvantage of the local receptive field of CNN, some recent registration methods have focused on using transformers for non-local registration. However, the standard Transformer has a vast number of parameters and high computational complexity, which causes Transformer can only be applied at the bottom of the registration models. As a result, only coarse information is available at the lowest resolution, limiting the contribution of Transformer in their models. To address these challenges, we propose a convolution-based efficient multi-head self-attention (CEMSA) block, which reduces the parameters of the traditional Transformer and captures local spatial context information for reducing semantic ambiguity in the attention mechanism. Based on the proposed CEMSA, we present a novel Symmetric Transformer-based model (SymTrans). SymTrans employs the Transformer blocks in the encoder and the decoder respectively to model the long-range spatial cross-image relevance. We apply SymTrans to the displacement field and diffeomorphic registration. Experimental results show that our proposed method achieves state-of-the-art performance in image registration. Our code is publicly available at \url{https://github.com/MingR-Ma/SymTrans}.
In current biological and medical research, statistical shape modeling (SSM) provides an essential framework for the characterization of anatomy/morphology. Such analysis is often driven by the identification of a relatively small number of geometrically consistent features found across the samples of a population. These features can subsequently provide information about the population shape variation. Dense correspondence models can provide ease of computation and yield an interpretable low-dimensional shape descriptor when followed by dimensionality reduction. However, automatic methods for obtaining such correspondences usually require image segmentation followed by significant preprocessing, which is taxing in terms of both computation as well as human resources. In many cases, the segmentation and subsequent processing require manual guidance and anatomy specific domain expertise. This paper proposes a self-supervised deep learning approach for discovering landmarks from images that can directly be used as a shape descriptor for subsequent analysis. We use landmark-driven image registration as the primary task to force the neural network to discover landmarks that register the images well. We also propose a regularization term that allows for robust optimization of the neural network and ensures that the landmarks uniformly span the image domain. The proposed method circumvents segmentation and preprocessing and directly produces a usable shape descriptor using just 2D or 3D images. In addition, we also propose two variants on the training loss function that allows for prior shape information to be integrated into the model. We apply this framework on several 2D and 3D datasets to obtain their shape descriptors, and analyze their utility for various applications.
We propose FlowReg, a deep learning-based framework for unsupervised image registration for neuroimaging applications. The system is composed of two architectures that are trained sequentially: FlowReg-A which affinely corrects for gross differences between moving and fixed volumes in 3D followed by FlowReg-O which performs pixel-wise deformations on a slice-by-slice basis for fine tuning in 2D. The affine network regresses the 3D affine matrix based on a correlation loss function that enforces global similarity. The deformable network operates on 2D image slices based on the optical flow network FlowNet-Simple but with three loss components. The photometric loss minimizes pixel intensity differences differences, the smoothness loss encourages similar magnitudes between neighbouring vectors, and a correlation loss that is used to maintain the intensity similarity between fixed and moving image slices. The proposed method is compared to four open source registration techniques ANTs, Demons, SE, and Voxelmorph. In total, 4643 FLAIR MR imaging volumes are used from dementia and vascular disease cohorts, acquired from over 60 international centres with varying acquisition parameters. A battery of quantitative novel registration validation metrics are proposed that focus on the structural integrity of tissues, spatial alignment, and intensity similarity. Experimental results show FlowReg (FlowReg-A+O) performs better than iterative-based registration algorithms for intensity and spatial alignment metrics with a Pixelwise Agreement of 0.65, correlation coefficient of 0.80, and Mutual Information of 0.29. Among the deep learning frameworks, FlowReg-A or FlowReg-A+O provided the highest performance over all but one of the metrics. Results show that FlowReg is able to obtain high intensity and spatial similarity while maintaining the shape and structure of anatomy and pathology.
In this work, we present a novel unsupervised image registration algorithm. It is differentiable end-to-end and can be used for both multi-modal and mono-modal registration. This is done using mutual information (MI) as a metric. The novelty here is that rather than using traditional ways of approximating MI, we use a neural estimator called MINE and supplement it with matrix exponential for transformation matrix computation. This leads to improved results as compared to the standard algorithms available out-of-the-box in state-of-the-art image registration toolboxes.