Objective: Clinical cardiac CT multiphase reconstructions generally provide acceptable image quality in end-diastole (ED) or end-systole (ES) phases, but in other phases may exhibit motion artifacts, especially in the right coronary artery (RCA). This limits ground-truth availability in 4D cardiac CT imaging research. We aim to construct a 4D cardiac CT dataset that is generally suitable to serve as pseudo ground truth. Methods: We propose Coronary Mask Guided Registration (CMGR) to produce a motion-preserved, artifact-reduced, and continuous-time 4D cardiac CT sequence from the clinical multiphase reconstruction of each patient. For artifact reduction, CMGR uses the ED or ES phase as the reference phase and warps the reference volume with deformation fields to produce the sequence. For motion preservation, CMGR registers the reference phase to each non-reference phase of the multiphase reconstruction. To capture the motion of both the RCA and other cardiac structures in each registration, CMGR regularizes RCA masks and incorporates them into image-domain registration. Time-continuity is achieved by interpolating the deformation fields for non-reference phases to arbitrary times. Results: CMGR outperformed representative image-domain registration methods in capturing RCA motion and providing reasonable RCA shape, and showed competitive performance in capturing whole-heart motion. Additionally, CMGR reduced motion artifacts from clinical multiphase reconstructions, and intermediate CMGR frames generally provided plausible transitions between discrete cardiac phases. Conclusion: CMGR provides an effective approach for constructing continuous-time 4D cardiac CT datasets. Significance: The dataset can be used in system design simulations and in reconstruction algorithm development, thereby facilitating advances in cardiac CT imaging.
Xiangyu Yin, Tatjana Paunesku, Letonia Copeland-Hardin +7cs.CV
Registering images acquired with different microscopy modalities is essential for relating complementary measurements of the same specimen. In correlative X-ray fluorescence (XRF) and optical microscopy, the XRF map often covers only a small region of an optical image acquired from the same or an adjacent tissue section. Field-of-view (FOV) localization is necessary but can be difficult when appearance and structure differ across modalities. Here we evaluate training-free vision language model (VLM) localization on two datasets representing same-section high-correspondence and adjacent-section low-correspondence imaging. We test unconstrained and metadata-constrained search and compare VLMs with geometric controls, classical template matching, and two alternative training-free approaches (DINOv2 and multiGradICON). Direct VLM prompting produced content-dependent spatial signals but was not reliable alone. Classical matching was most accurate when cross-modal structure was preserved but failed in the low-correspondence collection. A proposal-and-verify workflow used repeated VLM predictions as candidates and image-based similarity to select the final location. This workflow recovered useful localization in the low-correspondence regime.
Xiangyu Yin, Tatjana Paunesku, Letonia Copeland-Hardin +7cs.CV
X-ray fluorescence (XRF) microscopy maps elemental distributions, while optical microscopy can provide complementary morphological context. Localizing XRF fields of view (FOVs) in optical images is difficult because the two modalities differ in contrast mechanism and resolution. Most current workflows place each XRF tile independently, even when acquisition metadata already record the tiles' relative scan positions. This study formalizes XRF tile-group localization, in which one optical-frame placement is estimated for the whole group, constrained by acquisition geometry and quantified using group intersection-over-union (GroupIoU). In a controlled case study, independent localization failed with GroupIoU 0.000, whereas group localization achieved 0.931. Replacing the normalized cross-correlation (NCC) metric with mutual information (MI) gave nearly identical results, showing that the outcome is not specific to one local similarity metric. In another multiscale case study, using a coarse XRF survey scan to connect the fine-scale tile group to the optical image increased mean GroupIoU from 0.694 to 0.856. These case studies support using acquisition geometry as an explicit constraint when localizing related XRF tiles.
Rudolf L. M. van Herten, Robert Graf, Paula Feldman +1cs.CV
Aligning intraoperative biplanar digital subtraction angiography (DSA) to pre-procedural computed tomography angiography (CTA) requires rapid and accurate 3D-to-2D registration. Optimization-based methods are sensitive to initialization and may require hundreds of iterations, whereas learning-based approaches commonly rely on patient-specific training. We propose GeoPose, a population-trained framework that estimates the C-arm pose in a learned canonical frame and transfers it to the native frame of an unseen CTA through projection-space calibration and transform composition. A population-trained residual network refines the pose, followed optionally by low-budget image-driven optimization. GeoPose requires neither patient-specific adaptation nor explicit inter-volume preregistration. On 80 DSA observations from 20 held-out patients, optimization-free GeoPose achieved a carotid mean projected centerline distance (mPCD) of 5.8 mm and a clDice of 0.45, compared with 14.5 mm and 0.28 for the best-performing baseline, while requiring only 0.15 s. After 25 optimization iterations, GeoPose reached an mPCD of 4.6 mm and a clDice of 0.58 in approximately two seconds. Under the same budget, native-initialized optimization achieved 14.6 mm and 0.15, respectively. GeoPose thus provides rapid native-frame registration with fixed population-level weights and the geometric correspondence required for downstream biplanar 3D vascular reconstruction.
Bo Wen, Nehal Nailesh Mehta, Melanie Tran +3eess.IV cs.CV
Retinal image registration is essential for ophthalmic diagnosis, longitudinal disease monitoring, and multimodal retinal image analysis. Existing retinal registration methods are typically modality-dependent: they are designed or optimized either for a single imaging modality in mono-modal registration or for a fixed pair of modalities in cross-modal registration. This limits their flexibility and applicability in practical scenarios involving diverse retinal imaging modalities and different combinations of them. In this work, we propose a generalizable two-stage, modality-invariant framework for retinal image registration. First, we introduce a sparse feature-matching model driven by a universal retinal vessel segmentation to achieve robust coarse global alignment across modalities. Second, we develop a modality-invariant optical flow estimation network, termed MI-RAFT, to refine the alignment through dense local registration. Extensive experiments demonstrate that the proposed method can handle diverse combinations of commonly used retinal imaging modalities, exhibiting strong modality invariance while outperforming state-of-the-art modality-dependent registration methods.
Jingru Fu, Kathleen E. Larson, Douglas N. Greve +2eess.IV cs.AI q-bio.QM
Longitudinal MRI enables sensitive measurement of structural brain change for studying aging and neurodegenerative disease. Deformable image registration is a key tool for estimating such change by computing a dense deformation that captures geometric differences between longitudinal scans. However, MRI scanners introduce geometric distortions that vary across acquisition systems and protocols, such as gradient non-linearity (GNL) distortion. Existing registration methods estimate a single field that conflates biological and technical effects, potentially biasing downstream morphometric measurements if distortions remain (partially) uncorrected. We propose $\texttt{DisMorph}$, a registration framework trained entirely on synthetic data that explicitly decomposes longitudinal deformation into technical and anatomical transforms. It predicts two dense deformations, each encoding one effect. During training, a novel generative model synthesizes both effects separately to provide disentanglement supervision, while domain randomization promotes generalization across imaging protocols. We evaluate our method in three complementary settings. On simulated data with known ground truth, our method detects anatomical change more accurately and consistently than conventional registration. On real image pairs that differ only by GNL distortion, our method assigns most geometric change to the distortion field, demonstrating specificity in the absence of anatomical change. On longitudinal Alzheimer's disease (AD) pairs, our method detects anatomical change in AD-related brain structures while identifying residual distortion left after standard correction. By disentangling MRI-induced distortion from biological change in the longitudinal deformation, our method paves the way for more accurate longitudinal morphometry in clinical settings where maintaining acquisition consistency is challenging.
Registration-based Few-shot medical image segmentation (RFMIS) aims to generate pseudo-labels for unlabeled images by warping a labeled image through registration. However, existing methods primarily perform pixel-level optimization and inference in Euclidean space, treating anatomical structures as flat and disjoint. This neglect of inherent hierarchies degrades pseudo-label quality and weakens the discrimination of ambiguous regions, limiting the segmentation performance. To overcome this challenge, we propose a Hyperbolic Hierarchy-aware Aggregative Learning framework for RFMIS, termed H2AL, that enhances both deformation plausibility and anatomical discrimination for dual-task learning. Specifically, we introduce a Hyperbolic Hierarchy-aware Infusion (H2I) module, which leverages the hierarchical modeling capability of hyperbolic space to learn precise hierarchy-aware representations via transformation-guided supervised hyperbolic contrastive learning, and injects such hierarchical priors into Euclidean space through a gated infusion block while preserving semantic richness. Furthermore, we propose an end-to-end joint optimization algorithm by gradient aggregation, where the gradients from the registration and segmentation decoders, embedding semantic and hierarchical cues, are aggregated to update the shared encoder to promote collaborative learning across tasks. Extensive experiments on two anatomical regions, with five experimental settings, demonstrate the effectiveness and efficiency of our method in both registration and segmentation. The code is publicly available at https://github.com/JiamingCai469/H2AL.
In digital dentistry and oral surgery, the registration of jawbone CT and intraoral scanner (IOS) data is essential for integrating internal bone structure with high-resolution dental surface geometry. However, this registration is challenging because the two modalities share only a limited region in common, and their true correspondence is generally unknown. This uncertainty has prevented rigorous quantitative evaluation of registration accuracy. In this study, we propose a pseudoIOS evaluation framework in which a point cloud emulating an intraoral scan is generated from CT data within the same coordinate frame, so that the transformation between them is known by construction and can serve as a true ground truth. Using this framework, we propose a coarse-to-fine registration method that combines a domain-generalizable local descriptor (GeDi) for initialization-independent global alignment with the iterative closest point (ICP) algorithm for local refinement, and also evaluate the influence of metal artifacts on registration. In experiments on seven cases, ICP alone frequently converged to local minima from a perturbed initial position, whereas GeDi$+$ICP maintained submillimeter mean absolute error (MAE) across all evaluated jaw and artifact conditions (0.55-0.69 mm). A three-way repeated-measures analysis confirmed that GeDi$+$ICP was significantly more accurate than GeDi alone. Metal artifacts had a statistically detectable overall effect, but their absolute impact on GeDi$+$ICP was small.
White-light imaging (WLI) and narrow-band imaging (NBI) provide complementary views of endoscopic lesions, but their paired observations are often spatially misaligned due to viewpoint changes, tissue deformation, and sequential handheld acquisition. This makes direct WLI/NBI fusion prone to mixing non-corresponding regions and may even degrade segmentation around lesion boundaries. To address this problem, we propose a reliability-aware complex-domain fusion framework for paired-but-unregistered WLI/NBI lesion segmentation. The framework first establishes topology-regularized feature correspondence and further estimates where the cross-modal correspondence is reliable. Guided by this reliability, the model selectively fuses WLI and NBI features in a learnable complex representation. In this representation, WLI-derived cues mainly provide appearance-related magnitude responses, while NBI-derived cues provide structure-sensitive phase responses. Unlike conventional real-valued or symmetric multimodal fusion, the proposed method explicitly models the different roles of WLI and NBI and suppresses unreliable cross-modal interaction in locally mismatched regions. Experiments on paired WLI/NBI endoscopic datasets show that the proposed reliability-aware registration grounding and complex-domain fusion consistently improve lesion segmentation performance. Role-reversal and module ablation studies further validate the necessity of both the modality-role design and reliability-guided cross-modal interaction.
Antoine Legouhy, Ross Callaghan, Yuchuan Qiao +4cs.CV
Diffusion MRI (dMRI) relies on diffusion-weighted echo-planar imaging, which is highly susceptible to eddy-current-induced geometric distortions. These distortions vary across diffusion volumes according to gradient strength and direction, causing between-volume misalignment that can bias downstream microstructural analyses. Current state-of-the-art correction methods, such as FSL Eddy, achieve high-quality correction through iterative prediction-correction schemes but are computationally expensive. We propose Eddeep, a deep-learning framework for fast eddy-current distortion correction in dMRI. Eddeep decomposes the problem into two stages. First, a supervised image translation network standardises the appearance of diffusion-weighted and b=0 images, removing contrast differences that hinder reliable registration. Second, an unsupervised registration network estimates both eddy-current distortion and between-volume head motion parameters under a physics-constrained quadratic distortion model, enabling correction in a single forward pass. The method was trained on UK Biobank data and evaluated on both in-domain (UK Biobank) and out-of-domain (Memodyn) datasets. Across a range of complementary metrics, including between-volume jitter, diffusion kurtosis imaging residuals, signal irregularity, and mutual information, Eddeep achieved correction quality comparable to that of FSL Eddy while substantially reducing inference time. These results demonstrate that deep learning can provide accurate and efficient eddy-current distortion correction without relying on iterative optimisation, supporting the development of faster diffusion MRI processing pipelines for large-scale studies and clinical deployment. The code is available at: https://github.com/CIG-UCL/eddeep.
Functional magnetic resonance imaging (fMRI) utilizes echo-planar imaging (EPI) to capture blood-oxygen-level-dependent (BOLD) signals with high temporal resolution. However, EPI is inherently sensitive to magnetic field inhomogeneities, resulting in susceptibility-induced geometric distortions along the phase-encoding (PE) direction. To correct these distortions, conventional approaches rely on additional calibration scans, such as field maps or reverse PE acquisitions, which are not always available in practice. To overcome this limitation, we propose SACRED, a calibration scan-free susceptibility distortion correction framework that corrects geometric distortions via image translation-based registration using only a routinely acquired anatomical T1-weighted (T1w) image and a unidirectional PE BOLD image. SACRED employs an invertible neural network as the image translation backbone to bridge the contrast gap between BOLD and T1w images while enforcing structural consistency through a modality independent neighborhood descriptor. This design enables the use of a mono-contrast similarity objective to train the registration network in an unsupervised manner without requiring distortion-corrected BOLD images. In addition, we incorporate test-time adaptation (TTA) to further enhance performance on out-of-distribution (OOD) data at inference time. SACRED was evaluated on one in-distribution (ID) dataset and two OOD datasets, and was compared with representative fMRI distortion correction methods. The results demonstrate that SACRED significantly outperforms competing methods on both ID and OOD datasets, exhibiting robustness to scanner and population shifts, partly enabled by TTA. The code will be made publicly available upon acceptance.
Anna Bicchi, Alberto Rota, Leonardo Passoni +5cs.CV
Hyperspectral Imaging (HSI) is a promising modality for intraoperative assessment of resection margins in Breast-Conserving Surgery (BCS), but its clinical translation requires aligning the inherently 2D spectral information onto the 3D shape of the excised tissue so that suspicious regions can be precisely localized for targeted follow-up. We present a fully automated, calibration-free pipeline that produces a 3D hyperspectral point cloud of an ex-vivo lumpectomy specimen from a set of consumer-camera RGB images and a single top-down HSI acquisition. The 3D geometry is reconstructed with a deep-learning Structure-from-Motion backbone, stabilized in a metric reference frame by a custom bundle adjustment that enforces consistency on the corners of four ArUco markers placed around the specimen. The HSI cube is then registered to the reconstruction without recovering the HSI camera pose: the markers, visible in both modalities, define 16 corner correspondences that drive a planar homography, and 3D coordinates are recovered by lookup on an orthographically rendered depth map. Evaluated on two ex-vivo lumpectomy specimens, the pipeline achieves a median 3D registration error below 1~mm and a 2D reprojection error below 0.02 mm, with a total per-specimen processing time under 4 minutes on accelerated hardware. These results support the feasibility of integrating HSI-guided spatial localization into intraoperative margin assessment workflows for breast-conserving surgery.
Ana Sofia Santos, André Ferreira, Gijs Luijten +6eess.IV cs.AI cs.CV cs.LG
The nnU-Net has demonstrated continuous success in medical segmentation tasks, which heavily rely on the availability and diversity of annotated biomedical data. However, assembling medical imaging cohorts remains challenging due to numerous factors such as privacy regulations and annotation costs. As a result, data augmentation plays a crucial role in increasing data availability while maintaining anatomical feasibility. Hence, we propose the ++nnU-Net, a novel data augmentation module based on image registration that operates prior to preprocessing and training take place. Our framework was evaluated across five different 2D datasets. In this workflow, image data go through a two-stage registration process, generating new warped images. The transformations are then applied to the respective segmentation. In addition, the pipeline computes available disk space, generates supplementary binary synthetic masks and generates checkpoints. We demonstrate that the ++nnU-Net outperforms the nnU-Net baseline, yielding improvements in Dice Similarity Coefficient scores. In the most prominent cases, we observe performance gains of approximately 22\%. These findings highlight the effectiveness of registration-based data augmentation, particularly for 2D medical imaging datasets and suggest that the ++nnU-Net provides a practical and scalable approach for enhancing segmentation performance in data-limited settings. The source code for the ++nnU-Net is available at: https://github.com/sofia-adelie/plusplusnnunet.git
Santiago Cepeda, Olga Esteban-Sinovas, Ignacio Arrese +1cs.CV cs.LG
Maximal safe resection is the primary objective in glioma surgery. Neuronavigation guidance is progressively degraded by brain shift after dural opening. Intraoperative MRI can compensate but needs dedicated infrastructure and is rarely available, whereas intraoperative ultrasound (ioUS) is inexpensive, repeatable, and compatible with routine workflows. Navigation systems combining ioUS with preoperative MRI usually rely on rigid registration; even deformable multimodal registration is limited by ultrasound speckle contrast, a narrow field of view, and the inability to represent structures absent from the preoperative scan, most critically the resection cavity and residual tumor. We propose an end-to-end pipeline that generates a new whole-brain MRI volume in the preoperative imaging space by merging the preoperative MRI, a synthetic MRI generated from the ioUS, and a deformable registration anchored on that synthetic image. It integrates a 2.5D residual-transformer synthesis backbone (ResViT-2.5D) and a two-stage registration coupling NiftyReg with a synthesis-anchored SynthMorph stage, operating directly on raw scanner inputs. On a post-resection ReMIND cohort, ResViT-2.5D produced synthetic images closely matching the intraoperative T2 across structural, intensity, and perceptual metrics. In 14 subjects with 215 expert landmarks, the synthesis-anchored registration reduced the mean target registration error from 6.27 to 5.86 mm, matching a strong classical NiftyReg baseline (5.85 mm) while yielding a diffeomorphic deformation field in every subject. The contribution is not a gain in registration accuracy but the integrated volume itself, which inside the ultrasound field of view it reflects the intraoperative post-resection state. This provides the surgeon with an MRI-like update of the operative field with potential for integration into surgical-navigation workflows.
Roman Flepp, Arend Nieuwland, Bastian Sigrist +3cs.CV
Accurate execution of preoperative plans in corrective femoral osteotomies remains challenging. Current techniques are limited by variable accuracy, invasiveness, and radiation exposure, with free-hand methods and patient-specific instrumentation (PSI) often requiring >30 and >6 fluoroscopic images, respectively. We present an integrated, electromagnetic tracking (EMT)-based navigation system for femoral osteotomies that minimizes dissection and intraoperative fluoroscopy. The system couples CT-based preoperative planning with one-time intraoperative C-arm calibration and accurate X-ray-to-CT registration from two fluoroscopic images acquired at initialization. This enables real-time, fluoroscopy-free EMT navigation of the saw blade and bone fragments relative to the preoperative plan, and is compatible with uniplanar and biplanar osteotomies. In a feasibility study using 18 synthetic femora, EMT guidance significantly outperformed free-hand execution in total angular error ($(3.05 \pm 0.75)^\circ$ vs.\ $(6.32 \pm 2.36)^\circ$, $p=0.031$), assuming the same minimal surgical exposure for both. No EMT-guided trials exceeded the >5° clinical threshold, whereas free-hand produced 4 outliers of 6 trials. The system achieved statistical equivalence ($\pm 2^\circ$, $\pm 2,\text{mm}$) to PSI for total angular ($p \le 0.02$) and total translational ($p=0.048$) errors, with no significant differences in user questionnaire scores. By transferring preoperative plans using only two fluoroscopic images while matching PSI accuracy without additional surgical exposure, the proposed system motivates subsequent cadaveric and clinical validation.
Computed tomography (CT) is indispensable for clinical diagnosis and image-guided interventions but exposes patients to ionizing radiation, motivating the development of safer imaging alternatives. Ultrasound (US) is non-ionizing and widely accessible; however, it is highly operator dependent and lacks quantitative tissue characterization, often leading to diagnostic uncertainty and unnecessary CT examinations. This work presents a 3D ultrasound-derived pseudo-CT (UD-pCT) framework that generates CT-like anatomical reference volumes inferred from US, without aiming to reproduce physically accurate Hounsfield Units. Paired 3D kidney US and CT volumes from the TRUSTED dataset are first spatially aligned using a landmark-based multimodal registration pipeline, creating high-quality paired inputs for supervised training of an adversarial framework. The proposed Bottleneck Transformer Residual U-Net3D (BT-ResUNet3D) model employs a 3D residual encoder-decoder generator augmented with a transformer bottleneck, enabling effective modeling of fine-grained local anatomical structures as well as long-range volumetric dependencies, while a 3D Conditional PatchGAN discriminator enforces local structural realism in the synthesized pseudo-CT volumes. Quantitative evaluation using PSNR and SSIM demonstrates that the proposed method outperforms established baselines in structural fidelity and perceptual image quality. The UD-pCT volumes provide real-time anatomical reference for operator guidance, potentially reducing acquisition variability and unnecessary CT use. A limitation of this study is the relatively small paired dataset, which may limit the generalizability of the proposed model.