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Intensity-based image registration approaches rely on similarity measures to guide the search for geometric correspondences with high affinity between images. The properties of the used measure are vital for the robustness and accuracy of the registration. In this study a symmetric, intensity interpolation-free, affine registration framework based on a combination of intensity and spatial information is proposed. The excellent performance of the framework is demonstrated on a combination of synthetic tests, recovering known transformations in the presence of noise, and real applications in biomedical and medical image registration, for both 2D and 3D images. The method exhibits greater robustness and higher accuracy than similarity measures in common use, when inserted into a standard gradientbased registration framework available as part of the open source Insight Segmentation and Registration Toolkit (ITK). The method is also empirically shown to have a low computational cost, making it practical for real applications. Source code is available.

Distance transforms (DTs) are standard tools in image analysis, with applications in image registration and segmentation. The DT is based on extremal (minimal) distance values and is therefore highly sensitive to noise. We present a stochastic distance transform (SDT) based on discrete random sets, in which a model of element-wise probability is utilized and the SDT is computed as the first moment of the distance distribution to the random set. We present two methods for computing the SDT and analyze them w.r.t. accuracy and complexity. Further, we propose a method, utilizing kernel density estimation, for estimating probability functions and associated random sets to use with the SDT. We evaluate the accuracy of the SDT and the proposed framework on images of thin line structures and disks corrupted by salt and pepper noise and observe excellent performance. We also insert the SDT into a segmentation framework and apply it to overlapping objects, where it provides substantially improved performance over previous methods. Finally, we evaluate the SDT and observe very good performance, on simulated images from localization microscopy, a state-of-the-art super-resolution microscopy technique which yields highly spatially localized but noisy point-clouds.

We present INSPIRE, a top-performing general-purpose method for deformable image registration. INSPIRE brings distance measures which combine intensity and spatial information into an elastic B-splines-based transformation model and incorporates an inverse inconsistency penalization supporting symmetric registration performance. We introduce several theoretical and algorithmic solutions which provide high computational efficiency and thereby applicability of the proposed framework in a wide range of real scenarios. We show that INSPIRE delivers highly accurate, as well as stable and robust registration results. We evaluate the method on a 2D dataset created from retinal images, characterized by presence of networks of thin structures. Here INSPIRE exhibits excellent performance, substantially outperforming the widely used reference methods. We also evaluate INSPIRE on the Fundus Image Registration Dataset (FIRE), which consists of 134 pairs of separately acquired retinal images. INSPIRE exhibits excellent performance on the FIRE dataset, substantially outperforming several domain-specific methods. We also evaluate the method on four benchmark datasets of 3D magnetic resonance images of brains, for a total of 2088 pairwise registrations. A comparison with 17 other state-of-the-art methods reveals that INSPIRE provides the best overall performance. Code is available at github.com/MIDA-group/inspire

Multimodal image alignment is the process of finding spatial correspondences between images formed by different imaging techniques or under different conditions, to facilitate heterogeneous data fusion and correlative analysis. The information-theoretic concept of mutual information (MI) is widely used as a similarity measure to guide multimodal alignment processes, where most works have focused on local maximization of MI, which typically works well only for small displacements. This points to a need for global maximization of MI, which has previously been computationally infeasible due to the high run-time complexity of existing algorithms. We propose an efficient algorithm for computing MI for all discrete displacements (formalized as the cross-mutual information function (CMIF)), which is based on cross-correlation computed in the frequency domain. We show that the algorithm is equivalent to a direct method while superior in terms of run-time. Furthermore, we propose a method for multimodal image alignment for transformation models with few degrees of freedom (e.g., rigid) based on the proposed CMIF-algorithm. We evaluate the efficacy of the proposed method on three distinct benchmark datasets, containing remote sensing images, cytological images, and histological images, and we observe excellent success-rates (in recovering known rigid transformations), overall outperforming alternative methods, including local optimization of MI, as well as several recent deep learning-based approaches. We also evaluate the run-times of a GPU implementation of the proposed algorithm and observe speed-ups from 100 to more than 10,000 times for realistic image sizes compared to a GPU implementation of a direct method. Code is shared as open-source at github.com/MIDA-group/globalign.

Multimodal image alignment involves finding spatial correspondences between volumes varying in appearance and structure. Automated alignment methods are often based on local optimization that can be highly sensitive to their initialization. We propose a global optimization method for rigid multimodal 3D image alignment, based on a novel efficient algorithm for computing similarity of normalized gradient fields (NGF) in the frequency domain. We validate the method experimentally on a dataset comprised of 20 brain volumes acquired in four modalities (T1w, Flair, CT, [18F] FDG PET), synthetically displaced with known transformations. The proposed method exhibits excellent performance on all six possible modality combinations, and outperforms all four reference methods by a large margin. The method is fast; a 3.4Mvoxel global rigid alignment requires approximately 40 seconds of computation, and the proposed algorithm outperforms a direct algorithm for the same task by more than three orders of magnitude. Open-source implementation is provided.

We propose contrastive coding to learn shared, dense image representations, referred to as CoMIRs (Contrastive Multimodal Image Representations). CoMIRs enable the registration of multimodal images where existing registration methods often fail due to a lack of sufficiently similar image structures. CoMIRs reduce the multimodal registration problem to a monomodal one, in which general intensity-based, as well as feature-based, registration algorithms can be applied. The method involves training one neural network per modality on aligned images, using a contrastive loss based on noise-contrastive estimation (InfoNCE). Unlike other contrastive coding methods, used for, e.g., classification, our approach generates image-like representations that contain the information shared between modalities. We introduce a novel, hyperparameter-free modification to InfoNCE, to enforce rotational equivariance of the learnt representations, a property essential to the registration task. We assess the extent of achieved rotational equivariance and the stability of the representations with respect to weight initialization, training set, and hyperparameter settings, on a remote sensing dataset of RGB and near-infrared images. We evaluate the learnt representations through registration of a biomedical dataset of bright-field and second-harmonic generation microscopy images; two modalities with very little apparent correlation. The proposed approach based on CoMIRs significantly outperforms registration of representations created by GAN-based image-to-image translation, as well as a state-of-the-art, application-specific method which takes additional knowledge about the data into account. Code is available at: https://github.com/MIDA-group/CoMIR.

Despite current advancement in the field of biomedical image processing, propelled by the deep learning revolution, multimodal image registration, due to its several challenges, is still often performed manually by specialists. The recent success of image-to-image (I2I) translation in computer vision applications and its growing use in biomedical areas provide a tempting possibility of transforming the multimodal registration problem into a, potentially easier, monomodal one. We conduct an empirical study of the applicability of modern I2I translation methods for the task of multimodal biomedical image registration. We compare the performance of four Generative Adversarial Network (GAN)-based methods and one contrastive representation learning method, subsequently combined with two representative monomodal registration methods, to judge the effectiveness of modality translation for multimodal image registration. We evaluate these method combinations on three publicly available multimodal datasets of increasing difficulty, and compare with the performance of registration by Mutual Information maximisation and one modern data-specific multimodal registration method. Our results suggest that, although I2I translation may be helpful when the modalities to register are clearly correlated, registration of modalities which express distinctly different properties of the sample are not well handled by the I2I translation approach. When less information is shared between the modalities, the I2I translation methods struggle to provide good predictions, which impairs the registration performance. The evaluated representation learning method, which aims to find an in-between representation, manages better, and so does the Mutual Information maximisation approach. We share our complete experimental setup as open-source https://github.com/Noodles-321/Registration.