While contrast-enhanced CT (CECT) is standard for assessing abdominal aortic aneurysms (AAA) , the required iodinated contrast agents pose significant risks, including patient allergies and environmental harm. To reduce contrast agent use, methods have focused on generating synthetic CECT from non-contrast CT (NCCT) scans. However, most adopt a multi-stage pipeline that first generates images and then performs segmentation, which leads to error accumulation and fails to leverage shared information. To address this, we propose a unified framework that generates synthetic CECT images from NCCT scans while simultaneously segmenting the aortic lumen and thrombus. Our approach integrates conditional diffusion models (CDM) with multi-task learning, enabling end-to-end joint optimization of image synthesis and anatomical segmentation. Unlike previous multitask diffusion models, our approach requires no initial predictions (e.g., a coarse segmentation mask), shares both encoder and decoder parameters across tasks, and employs a semi-supervised training strategy to learn from scans with missing segmentation labels, a common constraint in clinical data. Evaluated on a cohort of 264 patients, our method consistently outperformed state-of-the-art single-task and multi-stage models. For image synthesis, it achieved a PSNR of 25.61 dB, compared to 23.80 dB from a single-task CDM. For segmentation, it improved the lumen Dice score to 0.89 from 0.87 and the challenging thrombus Dice score to 0.53 from 0.48 (nnU-Net). These segmentation enhancements led to more accurate clinical measurements, reducing the lumen diameter MAE to 4.19 mm from 5.78 mm and the thrombus area error to 33.85% from 41.45%. Code is at https://github.com/yuxuanou623/AortaDiff.

Cardiovascular disease (CVD) is one of the leading causes of death and illness across the world. Especially, early prediction of heart failure (HF) is complicated due to the heterogeneity of its clinical presentations and symptoms. These challenges underscore the need for a multidisciplinary approach for comprehensive evaluation of cardiac state. To this end, we specifically select electrocardiogram (ECG) and 3D cardiac anatomy for their complementary coverage of cardiac electrical activities and fine-grained structural modeling. Building upon this, we present a novel pre-training framework, named Anatomy-Electrocardiogram Model (AEM), to explore their complex interactions. AEM adopts a multi-task self-supervised scheme that combines a masked reconstruction objective with a cardiac measurement (CM) regression branch to embed cardiac functional priors and structural details. Unlike image-domain models that typically localize the whole heart within the image, our 3D anatomy is background-free and continuous in 3D space. Hence, the model can naturally concentrate on finer structures at the patch level. The further integration with ECG captures functional dynamics through electrical conduction, encapsulating holistic cardiac representations. Extensive experiments are conducted on the multi-modal datasets collected from the UK Biobank, which contain paired biventricular point cloud anatomy and 12-lead ECG data. Our proposed AEM achieves an area under the receiver operating characteristic curve of 0.8192 for incident HF prediction and a concordance index of 0.6976 for survival prediction under linear evaluation, outperforming the state-of-the-art multi-modal methods. Additionally, we study the interpretability of the disease prediction by observing that our model effectively recognizes clinically plausible patterns and exhibits a high association with clinical features.

Medical image segmentation remains challenging due to the high cost of pixel-level annotations for training. In the context of weak supervision, clinician gaze data captures regions of diagnostic interest; however, its sparsity limits its use for segmentation. In contrast, vision-language models (VLMs) provide semantic context through textual descriptions but lack the explanation precision required. Recognizing that neither source alone suffices, we propose a teacher-student framework that integrates both gaze and language supervision, leveraging their complementary strengths. Our key insight is that gaze data indicates "where" clinicians focus during diagnosis, while VLMs explain "why" those regions are significant. To implement this, the teacher model first learns from gaze points enhanced by VLM-generated descriptions of lesion morphology, establishing a foundation for guiding the student model. The teacher then directs the student through three strategies: 1) Multi-scale feature alignment to fuse visual cues with textual semantics; 2) Confidence-weighted consistency constraints to focus on reliable predictions; 3) Adaptive masking to limit error propagation in uncertain areas. Experiments on the Kvasir-SEG, NCI-ISBI, and ISIC datasets show that our method achieves Dice scores of 80.78%, 80.53%, and 84.22%, respectively-improving 3-5% over gaze baselines without increasing the annotation burden. By preserving correlations among predictions, gaze data, and lesion descriptions, our framework also maintains clinical interpretability. This work illustrates how integrating human visual attention with AI-generated semantic context can effectively overcome the limitations of individual weak supervision signals, thereby advancing the development of deployable, annotation-efficient medical AI systems. Code is available at: https://github.com/jingkunchen/FGI.

Junde Wu, Jiayuan Zhu, Yunli Qi, Jingkun Chen, Min Xu, Filippo Menolascina, Yueming Jin, Vicente Grau. Proceedings of the 63rd Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2025.

Cardiovascular diseases (CVDs) are the most common cause of death worldwide. Invasive x-ray coronary angiography (ICA) is one of the most important imaging modalities for the diagnosis of CVDs. ICA typically acquires only two 2D projections, which makes the 3D geometry of coronary vessels difficult to interpret, thus requiring 3D coronary artery tree reconstruction from two projections. State-of-the-art approaches require significant manual interactions and cannot correct the non-rigid cardiac and respiratory motions between non-simultaneous projections. In this study, we propose a novel deep learning pipeline named DeepCA. We leverage the Wasserstein conditional generative adversarial network with gradient penalty, latent convolutional transformer layers, and a dynamic snake convolutional critic to implicitly compensate for the non-rigid motion and provide 3D coronary artery tree reconstruction. Through simulating projections from coronary computed tomography angiography (CCTA), we achieve the generalisation of 3D coronary tree reconstruction on real non-simultaneous ICA projections. We incorporate an application-specific evaluation metric to validate our proposed model on both a CCTA dataset and a real ICA dataset, together with Chamfer £2 distance. The results demonstrate promising performance of our DeepCA model in vessel topology preservation, recovery of missing features, and generalisation ability to real ICA data. To the best of our knowledge, this is the first study that leverages deep learning to achieve 3D coronary tree reconstruction from two real non-simultaneous x-ray angiographic projections. The implementation of this work is available at: https//github.com/WangStephen/DeepCA.

Invasive coronary angiography (ICA) is the gold standard imaging modality during cardiac interventions. Accurate segmentation of coronary vessels in ICA is required for aiding diagnosis and creating treatment plans. Current automated algorithms for vessel segmentation face task-specific challenges, including motion artifacts and unevenly distributed contrast, as well as the general challenge inherent to X-ray imaging, which is the presence of shadows from overlapping organs in the background. To address these issues, we present Temporal Vessel Segmentation Network (TVS-Net) model that fuses sequential ICA information into a novel densely connected 3D encoder-2D decoder structure with a loss function based on elastic interaction. We develop our model using an ICA dataset comprising 323 samples, split into 173 for training, 82 for validation, and 68 for testing, with a relatively relaxed annotation protocol that produced coarse-grained samples, and achieve 83.4% Dice and 84.3% recall on the test dataset. We additionally perform an external evaluation over 60 images from a local hospital, achieving 78.5% Dice and 82.4% recall and outperforming the state-of-the-art approaches. We also conduct a detailed manual re-segmentation for evaluation only on a subset of the first dataset under strict annotation protocol, achieving a Dice score of 86.2% and recall of 86.3% and surpassing even the coarse-grained gold standard used in training. The results indicate our TVS-Net is effective for multi-frame ICA segmentation, highlights the network's generalizability and robustness across diverse settings, and showcases the feasibility of weak supervision in ICA segmentation.

Cardiac digital twins (CDTs) offer personalized in-silico cardiac representations for the inference of multi-scale properties tied to cardiac mechanisms. The creation of CDTs requires precise information about the electrode position on the torso, especially for the personalized electrocardiogram (ECG) calibration. However, current studies commonly rely on additional acquisition of torso imaging and manual/semi-automatic methods for ECG electrode localization. In this study, we propose a novel and efficient topology-informed model to fully automatically extract personalized ECG standard electrode locations from 2D clinically standard cardiac MRIs. Specifically, we obtain the sparse torso contours from the cardiac MRIs and then localize the standard electrodes of 12-lead ECG from the contours. Cardiac MRIs aim at imaging of the heart instead of the torso, leading to incomplete torso geometry within the imaging. To tackle the missing topology, we incorporate the electrodes as a subset of the keypoints, which can be explicitly aligned with the 3D torso topology. The experimental results demonstrate that the proposed model outperforms the time-consuming conventional model projection-based method in terms of accuracy (Euclidean distance: 1.24±0.293 cm vs. 1.48±0.362 cm) and efficiency (2 s vs. 30-35 min). We further demonstrate the effectiveness of using the detected electrodes for in-silico ECG simulation, highlighting their potential for creating accurate and efficient CDT models. The code is available at https://github.com/lileitech/12lead_ECG_electrode_localizer.

Heart failure (HF) poses a significant public health challenge, with a rising global mortality rate. Early detection and prevention of HF could significantly reduce its impact. We introduce a novel methodology for predicting HF risk using 12-lead electrocardiograms (ECGs). We present a novel, lightweight dual attention ECG network designed to capture complex ECG features essential for early HF risk prediction, despite the notable imbalance between low and high-risk groups. This network incorporates a cross-lead attention module and 12 lead-specific temporal attention modules, focusing on cross-lead interactions and each lead's local dynamics. To further alleviate model overfitting, we leverage a large language model (LLM) with a public ECG-Report dataset for pretraining on an ECG-Report alignment task. The network is then fine-tuned for HF risk prediction using two specific cohorts from the UK Biobank study, focusing on patients with hypertension (UKB-HYP) and those who have had a myocardial infarction (UKB-MI). The results reveal that LLM-informed pre-training substantially enhances HF risk prediction in these cohorts. The dual attention design not only improves interpretability but also predictive accuracy, outperforming existing competitive methods with C-index scores of 0.6349 for UKB-HYP and 0.5805 for UKB-MI. This demonstrates our method's potential in advancing HF risk assessment with clinical complex ECG data.

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions.

Global single-valued biomarkers, such as ejection fraction, are widely used in clinical practice to assess cardiac function. However, they only approximate the heart's true 3D deformation process, thus limiting diagnostic accuracy and the understanding of cardiac mechanics. Metrics based on 3D shape have been proposed to alleviate these shortcomings. In this work, we present the Point Cloud Deformation Network (PCD-Net) as a novel geometric deep learning approach for direct modeling of 3D cardiac mechanics of the biventricular anatomy between the extreme ends of the cardiac cycle. Its encoder-decoder architecture combines a low-dimensional latent space with recent advances in point cloud deep learning for effective multi-scale feature learning directly on flexible and memory-efficient point cloud representations of the cardiac anatomy. We first evaluate the PCD-Net's predictive capability for both cardiac contraction and relaxation on a large UK Biobank dataset of over 10,000 subjects and find average Chamfer distances between the predicted and ground truth anatomies below the pixel resolution of the underlying image acquisition. We then show the PCD-Net's ability to capture subpopulation-specific differences in 3D cardiac mechanics between normal and myocardial infarction (MI) subjects and visualize abnormal phenotypes between predicted normal 3D shapes and corresponding observed ones. Finally, we demonstrate that the PCD-Net's learned 3D deformation encodings outperform multiple clinical and machine learning benchmarks by 11% in terms of area under the receiver operating characteristic curve for the tasks of prevalent MI detection and incident MI prediction and by 7% in terms of Harrell's concordance index for MI survival analysis.

Cardiac digital twins (CDTs) have the potential to offer individualized evaluation of cardiac function in a non-invasive manner, making them a promising approach for personalized diagnosis and treatment planning of myocardial infarction (MI). The inference of accurate myocardial tissue properties is crucial in creating a reliable CDT of MI. In this work, we investigate the feasibility of inferring myocardial tissue properties from the electrocardiogram (ECG) within a CDT platform. The platform integrates multi-modal data, such as cardiac MRI and ECG, to enhance the accuracy and reliability of the inferred tissue properties. We perform a sensitivity analysis based on computer simulations, systematically exploring the effects of infarct location, size, degree of transmurality, and electrical activity alteration on the simulated QRS complex of ECG, to establish the limits of the approach. We subsequently present a novel deep computational model, comprising a dual-branch variational autoencoder and an inference model, to infer infarct location and distribution from the simulated QRS. The proposed model achieves mean Dice scores of 0.457 ±0.317 and 0.302 ±0.273 for the inference of left ventricle scars and border zone, respectively. The sensitivity analysis enhances our understanding of the complex relationship between infarct characteristics and electrophysiological features. The in silico experimental results show that the model can effectively capture the relationship for the inverse inference, with promising potential for clinical application in the future. The code is available at https://github.com/lileitech/MI_inverse_inference.

Cine magnetic resonance imaging (MRI) is the current gold standard for the assessment of cardiac anatomy and function. However, it typically only acquires a set of two-dimensional (2D) slices of the underlying three-dimensional (3D) anatomy of the heart, thus limiting the understanding and analysis of both healthy and pathological cardiac morphology and physiology. In this paper, we propose a novel fully automatic surface reconstruction pipeline capable of reconstructing multi-class 3D cardiac anatomy meshes from raw cine MRI acquisitions. Its key component is a multi-class point cloud completion network (PCCN) capable of correcting both the sparsity and misalignment issues of the 3D reconstruction task in a unified model. We first evaluate the PCCN on a large synthetic dataset of biventricular anatomies and observe Chamfer distances between reconstructed and gold standard anatomies below or similar to the underlying image resolution for multiple levels of slice misalignment. Furthermore, we find a reduction in reconstruction error compared to a benchmark 3D U-Net by 32% and 24% in terms of Hausdorff distance and mean surface distance, respectively. We then apply the PCCN as part of our automated reconstruction pipeline to 1000 subjects from the UK Biobank study in a cross-domain transfer setting and demonstrate its ability to reconstruct accurate and topologically plausible biventricular heart meshes with clinical metrics comparable to the previous literature. Finally, we investigate the robustness of our proposed approach and observe its capacity to successfully handle multiple common outlier conditions.

Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, either combining information from different modalities or transferring information across modalities. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, modality selection, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future.

In recent years, several deep learning models have been proposed to accurately quantify and diagnose cardiac pathologies. These automated tools heavily rely on the accurate segmentation of cardiac structures in MRI images. However, segmentation of the right ventricle is challenging due to its highly complex shape and ill-defined borders. Hence, there is a need for new methods to handle such structure's geometrical and textural complexities, notably in the presence of pathologies such as Dilated Right Ventricle, Tricuspid Regurgitation, Arrhythmogenesis, Tetralogy of Fallot, and Inter-atrial Communication. The last MICCAI challenge on right ventricle segmentation was held in 2012 and included only 48 cases from a single clinical center. As part of the 12th Workshop on Statistical Atlases and Computational Models of the Heart (STACOM 2021), the M&Ms-2 challenge was organized to promote the interest of the research community around right ventricle segmentation in multi-disease, multi-view, and multi-center cardiac MRI. Three hundred sixty CMR cases, including short-axis and long-axis 4-chamber views, were collected from three Spanish hospitals using nine different scanners from three different vendors, and included a diverse set of right and left ventricle pathologies. The solutions provided by the participants show that nnU-Net achieved the best results overall. However, multi-view approaches were able to capture additional information, highlighting the need to integrate multiple cardiac diseases, views, scanners, and acquisition protocols to produce reliable automatic cardiac segmentation algorithms.

The realisation of precision cardiology requires novel techniques for the non-invasive characterisation of individual patients’ cardiac function to inform therapeutic and diagnostic decision-making. Both electrocardiography and imaging are used for the clinical diagnosis of cardiac disease. The integration of multi-modal datasets through advanced computational methods could enable the development of the cardiac ‘digital twin’, a comprehensive virtual tool that mechanistically reveals a patient's heart condition from clinical data and simulates treatment outcomes. The adoption of cardiac digital twins requires the non-invasive efficient personalisation of the electrophysiological properties in cardiac models. This study develops new computational techniques to estimate key ventricular activation properties for individual subjects by exploiting the synergy between non-invasive electrocardiography, cardiac magnetic resonance (CMR) imaging and modelling and simulation. More precisely, we present an efficient sequential Monte Carlo approximate Bayesian computation-based inference method, integrated with Eikonal simulations and torso-biventricular models constructed based on clinical CMR imaging. The method also includes a novel strategy to treat combined continuous (conduction speeds) and discrete (earliest activation sites) parameter spaces and an efficient dynamic time warping-based ECG comparison algorithm. We demonstrate results from our inference method on a cohort of twenty virtual subjects with cardiac ventricular myocardial-mass volumes ranging from 74 cm3 to 171 cm3 and considering low versus high resolution for the endocardial discretisation (which determines possible locations of the earliest activation sites). Results show that our method can successfully infer the ventricular activation properties in sinus rhythm from non-invasive epicardial activation time maps and ECG recordings, achieving higher accuracy for the endocardial speed and sheet (transmural) speed than for the fibre or sheet-normal directed speeds.

Automatic quantification of the left ventricle (LV) from cardiac magnetic resonance (CMR) images plays an important role in making the diagnosis procedure efficient, reliable, and alleviating the laborious reading work for physicians. Considerable efforts have been devoted to LV quantification using different strategies that include segmentation-based (SG) methods and the recent direct regression (DR) methods. Although both SG and DR methods have obtained great success for the task, a systematic platform to benchmark them remains absent because of differences in label information during model learning. In this paper, we conducted an unbiased evaluation and comparison of cardiac LV quantification methods that were submitted to the Left Ventricle Quantification (LVQuan) challenge, which was held in conjunction with the Statistical Atlases and Computational Modeling of the Heart (STACOM) workshop at the MICCAI 2018. The challenge was targeted at the quantification of 1) areas of LV cavity and myocardium, 2) dimensions of the LV cavity, 3) regional wall thicknesses (RWT), and 4) the cardiac phase, from mid-ventricle short-axis CMR images. First, we constructed a public quantification dataset Cardiac-DIG with ground truth labels for both the myocardium mask and these quantification targets across the entire cardiac cycle. Then, the key techniques employed by each submission were described. Next, quantitative validation of these submissions were conducted with the constructed dataset. The evaluation results revealed that both SG and DR methods can offer good LV quantification performance, even though DR methods do not require densely labeled masks for supervision. Among the 12 submissions, the DR method LDAMT offered the best performance, with a mean estimation error of 301 mm2for the two areas, 2.15 mm for the cavity dimensions, 2.03 mm for RWTs, and a 9.5% error rate for the cardiac phase classification. Three of the SG methods also delivered comparable performances. Finally, we discussed the advantages and disadvantages of SG and DR methods, as well as the unsolved problems in automatic cardiac quantification for clinical practice applications.

X-ray angiography is the most commonly used imaging modality for the detection of coronary stenoses due to its high spatial and temporal resolution of lumen contour and its utility to guide coronary interventions in real time. However, the high inter- and intra-observer variability in interpreting the geometry of 3D vascular structure based on multiple 2D image projections is a limitation in the accurate determination of lesion severity. This could be addressed by the 3D reconstruction of the coronary arterial (CA) tree. The automated reconstruction of 3D CA tree from 2D projections is challenging due to the existence of several imaging artifacts, such as vessel overlap, foreshortening, and most importantly respiratory and cardiac motion. Along with these artifacts, the acquisition geometry introduces the possibility of generating false vessel segments in the reconstruction. Our approach aims to reduce the motion artifacts in angiographic projections by developing a new method for rigid and non-rigid motion correction. A novel point-cloud based approach is subsequently introduced for reconstruction of 3D vessel centerlines by iteratively minimizing the reconstruction error. The performance of the proposed 3D reconstruction is evaluated using angiographic projections from 45 patients, producing average reprojection errors of 0.092 ±0.055 mm and 0.910 ±0.352 mm for 3D centerlines reconstruction, when co-registered with the parent vessels on projection planes that were/were not used to derive the 3D reconstruction, respectively. A comparison of the reconstructed 3D lumen surface with optical coherence tomography (OCT) measurements has been performed, showing no statistically significant difference in the luminal cross-sections reconstructed with our method, compared to OCT.

Vasculature is known to be of key biological significance, especially in the study of tumors. As such, considerable effort has been focused on the automated segmentation of vasculature in medical and pre-clinical images. The majority of vascular segmentation methods focus on bloodpool labeling methods; however, particularly, in the study of tumors, it is of particular interest to be able to visualize both the perfused and the non-perfused vasculature. Imaging vasculature by highlighting the endothelium provides a way to separate the morphology of vasculature from the potentially confounding factor of perfusion. Here, we present a method for the segmentation of tumor vasculature in 3D fluorescence microscopic images using signals from the endothelial and surrounding cells. We show that our method can provide complete and semantically meaningful segmentations of complex vasculature using a supervoxel-Markov random field approach. We show that in terms of extracting meaningful segmentations of the vasculature, our method outperforms both state-of-the-art method, specific to these data, as well as more classical vasculature segmentation methods.

Statistical shape modeling is a powerful tool for visualizing and quantifying geometric and functional patterns of the heart. After myocardial infarction (MI), the left ventricle typically remodels in response to physiological challenges. Several methods have been proposed in the literature to describe statistical shape changes. Which method best characterizes left ventricular remodeling after MI is an open research question. A better descriptor of remodeling is expected to provide a more accurate evaluation of disease status in MI patients. We therefore designed a challenge to test shape characterization in MI given a set of three-dimensional left ventricular surface points. The training set comprised 100 MI patients, and 100 asymptomatic volunteers (AV). The challenge was initiated in 2015 at the Statistical Atlases and Computational Models of the Heart workshop, in conjunction with the MICCAI conference. The training set with labels was provided to participants, who were asked to submit the likelihood of MI from a different (validation) set of 200 cases (100 AV and 100 MI). Sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were used as the outcome measures. The goals of this challenge were to (1) establish a common dataset for evaluating statistical shape modeling algorithms in MI, and (2) test whether statistical shape modeling provides additional information characterizing MI patients over standard clinical measures. Eleven groups with a wide variety of classification and feature extraction approaches participated in this challenge. All methods achieved excellent classification results with accuracy ranges from 0.83 to 0.98. The areas under the receiver operating characteristic curves were all above 0.90. Four methods showed significantly higher performance than standard clinical measures. The dataset and software for evaluation are available from the Cardiac Atlas Project website1.

Traditional histology is the gold standard for tissue studies, but it is intrinsically reliant on two-dimensional (2D) images. Study of volumetric tissue samples such as whole hearts produces a stack of misaligned and distorted 2D images that need to be reconstructed to recover a congruent volume with the original sample's shape. In this paper, we develop a mathematical framework called Transformation Diffusion (TD) for stack alignment refinement as a solution to the heat diffusion equation. This general framework does not require contour segmentation, is independent of the registration method used, and is trivially parallelizable. After the first stack sweep, we also replace registration operations by operations in the space of transformations, several orders of magnitude faster and less memory-consuming. Implementing TD with operations in the space of transformations produces our Transformation Diffusion Reconstruction (TDR) algorithm, applicable to general transformations that are closed under inversion and composition. In particular, we provide formulas for translation and affine transformations. We also propose an Approximated TDR (ATDR) algorithm that extends the same principles to tensor-product B-spline transformations. Using TDR and ATDR, we reconstruct a full mouse heart at pixel size 0.92µm×0.92µm, cut 10µm thick, spaced 20µm (84G). Our algorithms employ only local information from transformations between neighboring slices, but the TD framework allows theoretical analysis of the refinement as applying a global Gaussian low-pass filter to the unknown stack misalignments. We also show that reconstruction without an external reference produces large shape artifacts in a cardiac specimen while still optimizing slice-to-slice alignment. To overcome this problem, we use a pre-cutting blockface imaging process previously developed by our group that takes advantage of Brewster's angle and a polarizer to capture the outline of only the topmost layer of wax in the block containing embedded tissue for histological sectioning.

A model of cardiac microstructure and diffusion MRI is presented, and compared with experimental data from ex vivo rat hearts. The model includes a simplified representation of individual cells, with physiologically correct cell size and orientation, as well as intra- to extracellular volume ratio. Diffusion MRI is simulated using a Monte Carlo model and realistic MRI sequences. The results show good correspondence between the simulated and experimental MRI signals. Similar patterns are observed in the eigenvalues of the diffusion tensor, the mean diffusivity (MD), and the fractional anisotropy (FA). A sensitivity analysis shows that the diffusivity is the dominant influence on all three eigenvalues of the diffusion tensor, the MD, and the FA. The area and aspect ratio of the cell cross-section affect the secondary and tertiary eigenvalues, and hence the FA. Within biological norms, the cell length, volume fraction of cells, and rate of change of helix angle play a relatively small role in influencing tissue diffusion. Results suggest that the model could be used to improve understanding of the relationship between cardiac microstructure and diffusion MRI measurements, as well as in testing and refinement of cardiac diffusion MRI protocols.

Diffusion in biological tissues is known to be hindered by the structural complexity of the underlying medium. In the heart, improved characterisation on how this complexity influences acquired diffusion weighted signals is key to advancing our interpretation of diffusion magnetic resonance imaging, as well as to propose novel biomarkers to further characterise myocardial microstructure. In this work, we propose stretched Mittag-Leffler signal decay models for the quantification of the anomalous decay observed in acquired diffusion weighted signals. Our results, analysed in ex vivo healthy, fixed rat ventricles, indicate that such a representation suffices to capture the anomalous signal decay observed in the myocardial syncytium. The subdiffusive order of signal decay is shown to encode independent information to that encapsulated by standard diffusion tensor metrics, and thus may provide additional information on tissue microstructure. Moreover, subdiffusion gradients are shown to be indicative of the total structural heterogeneity spanning the left ventricular wall, which includes progressive myolaminae branching and spatially varying densities of perimysial collagen, microvasculature and adipose tissue. The proposed approach may therefore have important implications for the characterisation of tissue microstructure, both in cardiac and other tissue types.

A novel method for real-time magnetic resonance imaging for the assessment of cardiac function in mice at 9.4 T is proposed. The technique combines a highly undersampled radial gradient echo acquisition with an image reconstruction utilizing both parallel imaging and compressed sensing. Simulations on an in silico phantom were performed to determine the achievable acceleration factor and to optimize regularization parameters. Several parameters characterizing the quality of the reconstructed images (such as spatial and temporal image sharpness or compartment areas) were calculated for this purpose. Subsequently, double-gated segmented cine data as well as non-gated undersampled real-time data using only six projections per timeframe (temporal resolution ∼ 10 ms) were acquired in a mid-ventricular slice of four normal mouse hearts in vivo. The highly accelerated data sets were then subjected to the introduced reconstruction technique and results were validated against the fully sampled references. Functional parameters obtained from real-time and fully sampled data agreed well with a comparable accuracy for left-ventricular volumes and a slightly larger scatter for mass. This study introduces and validates a real-time cine-MRI technique, which significantly reduces scan time in preclinical cardiac functional imaging and has the potential to investigate mouse models with abnormal heart rhythm.

BACKGROUND: Microscopy image segmentation lays the foundation for shape analysis, motion tracking, and classification of biological objects. Despite its importance, automated segmentation remains challenging for several widely used non-fluorescence, interference-based microscopy imaging modalities. For example in differential interference contrast microscopy which plays an important role in modern bacterial cell biology. Therefore, new revolutions in the field require the development of tools, technologies and work-flows to extract and exploit information from interference-based imaging data so as to achieve new fundamental biological insights and understanding. RESULTS: We have developed and evaluated a high-throughput image analysis and processing approach to detect and characterize bacterial cells and chemotaxis proteins. Its performance was evaluated using differential interference contrast and fluorescence microscopy images of Rhodobacter sphaeroides. CONCLUSIONS: Results demonstrate that the proposed approach provides a fast and robust method for detection and analysis of spatial relationship between bacterial cells and their chemotaxis proteins.

The aim of this study was to develop a novel method to reconstruct 3-D coronary vasculature from cryomicrotome images, comprised of two distinct sets of data-fluorescent microsphere beads and coronary vasculature. Fluorescent beads and cast injected into the vasculature were separately imaged with different filter settings to obtain the microsphere and vascular data, respectively. To extract the vascular anatomy, light scattering in the tissue was modelled using a point spread function (PSF). The PSF was parametrized by optical tissue excitation and emission attenuation coefficients, which were estimated by fitting simulated images of microspheres convolved with the PSF model to the experimental microsphere images. These parameters were then applied within a new model-based method for vessel radius estimation. Current state-of-the-art radii estimation methods and the proposed model-based method were applied on vessel phantoms. In this validation study, the full-width half-maximum method of radii estimation, when performed on the raw data without correcting for the optical blurring, resulted in 42.9% error on average for the 170 μm vessel. In comparison, the model-based method resulted in 0.6% error on average for the same phantom. Whole-organ porcine coronary vasculature was automatically reconstructed with the new model-based vascular extraction method.

MOTIVATION: Fungi form extensive interconnected mycelial networks that scavenge efficiently for scarce resources in a heterogeneous environment. The architecture of the network is highly responsive to local nutritional cues, damage or predation, and continuously adapts through growth, branching, fusion or regression. These networks also provide an example of an experimental planar network system that can be subjected to both theoretical analysis and experimental manipulation in multiple replicates. For high-throughput measurements, with hundreds of thousands of branches on each image, manual detection is not a realistic option, especially if extended time series are captured. Furthermore, branches typically show considerable variation in contrast as the individual cords span several orders of magnitude and the compressed soil substrate is not homogeneous in texture making automated segmentation challenging. RESULTS: We have developed and evaluated a high-throughput automated image analysis and processing approach using Phase Congruency Tensors and watershed segmentation to characterize complex fungal networks. The performance of the proposed approach is evaluated using complex images of saprotrophic fungal networks with 10(5)-10(6) edges. The results obtained demonstrate that this approach provides a fast and robust solution for detection and graph-based representation of complex curvilinear networks. AVAILABILITY AND IMPLEMENTATION: The Matlab toolbox is freely available through the Oxford e-Research Centre website: http://www.oerc.ox.ac.uk/research/bioimage/software CONTACTS: [email protected].

Many biomedical applications require detection of curvilinear structures in images and would benefit from automatic or semiautomatic segmentation to allow high-throughput measurements. Here, we propose a contrast-independent approach to identify curvilinear structures based on oriented phase congruency, i.e., the phase congruency tensor (PCT). We show that the proposed method is largely insensitive to intensity variations along the curve and provides successful detection within noisy regions. The performance of the PCT is evaluated by comparing it with state-of-the-art intensity-based approaches on both synthetic and real biological images.

Real-time 3-D echocardiography opens up the possibility of interactive, fast 3-D analysis of cardiac anatomy and function. However, at the present time its quantitative power cannot be fully exploited due to the limited quality of the images. In this paper, we present an algorithm to register apical and parasternal echocardiographic datasets that uses a new similarity measure, based on local orientation and phase differences. By using phase and orientation to guide registration, the effect of artifacts intrinsic to ultrasound images is minimized. The presented method is fully automatic except for initialization. The accuracy of the method was validated qualitatively, resulting in 85% of the cardiac segments estimated having a registration error smaller than 2 mm, and no segments with an error larger than 5 mm. Robustness with respect to landmark initialization was validated quantitatively, with average errors smaller than 0.2 mm and 0.5 degrees for initialization landmarks rotations of up to 15 degrees and translations of up to 10 mm.

The study of the architecture of the optic nerve head (ONH) may provide valuable information about the development and progression of glaucoma. To this end, we have generated three-dimensional datasets from monkey eyes under controlled intraocular pressure (IOP). Segmentation of the connective tissues in this area is crucial to obtain an accurate measurement of geometrical parameters and to build mechanical models. However, this segmentation is made difficult by the complicated geometry and the artifacts introduced in the dataset building process. We present a novel segmentation algorithm, based on expectation-maximization, which incorporates an anisotropic Markov random field (MRF) to introduce prior knowledge about the geometry of the structure. The structure tensor is used to characterize the predominant structure direction and the spatial coherence at each point. The algorithm, which has been validated on an artificial validation dataset that mimics our ONH datasets, shows significant improvement over an isotropic MRF. Results on the real datasets demonstrate the ability of the new algorithm to obtain accurate, spatially consistent segmentations of this structure.

The watershed transform has interesting properties that make it useful for many different image segmentation applications: it is simple and intuitive, can be parallelized, and always produces a complete division of the image. However, when applied to medical image analysis, it has important drawbacks (oversegmentation, sensitivity to noise, poor detection of thin or low signal to noise ratio structures). We present an improvement to the watershed transform that enables the introduction of prior information in its calculation. We propose to introduce this information via the use of a previous probability calculation. Furthermore, we introduce a method to combine the watershed transform and atlas registration, through the use of markers. We have applied our new algorithm to two challenging applications: knee cartilage and gray matter/white matter segmentation in MR images. Numerical validation of the results is provided, demonstrating the strength of the algorithm for medical image segmentation.