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Computer aided pathological analysis has been the gold standard for tumor diagnosis, however domain shift is a significant problem in histopathology. It may be caused by variability in anatomical structures, tissue preparation, and imaging processes challenges the robustness of segmentation models. In this work, we present a framework consist of pre-trained encoder with a Swin-UNet architecture enhanced by a parallel cross-attention module to tackle the problem of adenocarcinoma segmentation across different organs and scanners, considering both morphological changes and scanner-induced domain variations. Experiment conducted on Cross-Organ and Cross-Scanner Adenocarcinoma Segmentation challenge dataset showed that our framework achieved segmentation scores of 0.7469 for the cross-organ track and 0.7597 for the cross-scanner track on the final challenge test sets, and effectively navigates diverse imaging conditions and improves segmentation accuracy across varying domains., Comment: 6 pages 2 figures

Cardiac magnetic resonance (CMR) imaging and computed tomography (CT) are two common non-invasive imaging methods for assessing patients with cardiovascular disease. CMR typically acquires multiple sparse 2D slices, with unavoidable respiratory motion artefacts between slices, whereas CT acquires isotropic dense data but uses ionising radiation. In this study, we explore the combination of Slice Shifting Algorithm (SSA), Spatial Transformer Network (STN), and Label Transformer Network (LTN) to: 1) correct respiratory motion between segmented slices, and 2) transform sparse segmentation data into dense segmentation. All combinations were validated using synthetic motion-corrupted CMR slice segmentation generated from CT in 1699 cases, where the dense CT serves as the ground truth. In 199 testing cases, SSA-LTN achieved the best results for Dice score and Huasdorff distance (94.0% and 4.7 mm respectively, average over 5 labels) but gave topological errors in 8 cases. STN was effective as a plug-in tool for correcting all topological errors with minimal impact on overall performance (93.5% and 5.0 mm respectively). SSA also proves to be a valuable plug-in tool, enhancing performance over both STN-based and LTN-based models. The code for these different combinations is available at https://github.com/XESchong/STACOM2024., Comment: 13 pages, STACOM2024

Automated segmentation of Cardiac Magnetic Resonance (CMR) plays a pivotal role in efficiently assessing cardiac function, offering rapid clinical evaluations that benefit both healthcare practitioners and patients. While recent research has primarily focused on delineating structures in the short-axis orientation, less attention has been given to long-axis representations, mainly due to the complex nature of structures in this orientation. Performing pixel-wise segmentation of the left ventricular (LV) myocardium and the four cardiac chambers in 2-D steady-state free precession (SSFP) cine sequences is a crucial preprocessing stage for various analyses. However, the challenge lies in the significant variability in contrast, appearance, orientation, and positioning of the heart across different patients, clinical views, scanners, and imaging protocols. Consequently, achieving fully automatic semantic segmentation in this context is notoriously challenging. 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 magnetic resonance images (MRI). Hence, there is a need for new methods to handle such structures' geometrical and textural complexities. We proposed 2D and 3D two-stage self-supervised deep learning segmentation hybrid transformer and CNN-based architectures for 4CH whole heart segmentation. Accurate segmentation of the ventricles and atria in 4CH views is crucial for analyzing heart health and reconstructing four-chamber meshes, which are essential for estimating various parameters to assess overall heart condition. Our proposed method outperformed state-of-the-art techniques, demonstrating superior performance in this domain., Comment: arXiv admin note: text overlap with arXiv:2206.07349 by other authors

Unlike Right Atrium (RA), Left Atrium (LA) presents distinctive challenges, including much thinner myocardial walls, complex and irregular morphology, as well as diversity in individual's structure, making off-the-shelf methods designed for the Left Ventricle (LV) may not work in the context of the left atrium. To overcome aforementioned challenges, we are the first to present comprehensive technical workflow designed for 4D registration modeling to automatically analyze LA motion using high-resolution 3D Cine MR images. We integrate segmentation network and 4D registration process to precisely delineate LA segmentation throughout the full cardiac cycle. Additionally, an image 4D registration network is employed to extract LA displacement vector fields (DVFs). Our findings show the potential of proposed end to end framework in providing clinicians with novel regional biomarkers for left atrium motion tracking and deformation, carrying significant clinical implications.

Cardiac digital twins provide a physics and physiology informed framework to deliver predictive and personalized medicine. However, high-fidelity multi-scale cardiac models remain a barrier to adoption due to their extensive computational costs and the high number of model evaluations needed for patient-specific personalization. Artificial Intelligence-based methods can make the creation of fast and accurate whole-heart digital twins feasible. In this work, we use Latent Neural Ordinary Differential Equations (LNODEs) to learn the temporal pressure-volume dynamics of a heart failure patient. Our surrogate model based on LNODEs is trained from 400 3D-0D whole-heart closed-loop electromechanical simulations while accounting for 43 model parameters, describing single cell through to whole organ and cardiovascular hemodynamics. The trained LNODEs provides a compact and efficient representation of the 3D-0D model in a latent space by means of a feedforward fully-connected Artificial Neural Network that retains 3 hidden layers with 13 neurons per layer and allows for 300x real-time numerical simulations of the cardiac function on a single processor of a standard laptop. This surrogate model is employed to perform global sensitivity analysis and robust parameter estimation with uncertainty quantification in 3 hours of computations, still on a single processor. We match pressure and volume time traces unseen by the LNODEs during the training phase and we calibrate 4 to 11 model parameters while also providing their posterior distribution. This paper introduces the most advanced surrogate model of cardiac function available in the literature and opens new important venues for parameter calibration in cardiac digital twins.

We present an open-source software pipeline to create patient-specific left atrial (LA) models with fibre orientations and a fibrosis map, suitable for electrophysiology simulations. The semi-automatic pipeline takes as input a contrast enhanced magnetic resonance angiogram, and a late gadolinium enhanced (LGE) contrast magnetic resonance (CMR). Five operators were allocated 20 cases each from a set of 50 CMR datasets to create a total of 100 models to evaluate inter/intra-operator variability. Each output model consisted of (1) a labelled surface mesh open at the pulmonary veins (PV) and mitral valve (MV), (2) fibre orientations mapped from a diffusion tensor MRI human atlas, (3) fibrosis map from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. We evaluated reproducibility in our pipeline by comparing agreement in shape of the output meshes, fibrosis distribution in the LA body, and fibre orientations; simulations outputs were evaluated comparing total activation times of LAT maps, mean conduction velocity (CV), and structural similarity index measure (SSIM) of PS maps. Our workflow allows a single model to be created in 16.72 +/- 12.25 minutes. Results in this abstract are reported as inter/intra. Shape only differed noticeably with users' selection of the MV and the length of the PV from the ostia to the distal end; fibrosis agreement (0.91/0.99 ICC) and fibre orientation agreement (60.63/71.77 %) were high. LAT maps showed good agreement, the median of the absolute difference of the total activation times was 2.02ms/1.37ms. The average of the mean CV difference was -4.04mm/s / 2.1mm/s. PS maps showed a moderately good agreement with SSIM of 0.648/0.608. Although we found notable differences in the models due to user input, our tests show that operator variability was comparable to that of image resolution or fibre estimation., Comment: 17 pages, 7 figures, submitted for review at Journal of Computers in Biology and Medicine (in press)

Over the past two decades there has been a steady trend towards the development of realistic models of cardiac conduction with increasing levels of detail. However, making models more realistic complicates their personalization and use in clinical practice due to limited availability of tissue and cellular scale data. One such limitation is obtaining information about myocardial fiber organization in the clinical setting. In this study, we investigated a chimeric model of the left atrium utilizing clinically derived patient-specific atrial geometry and a realistic, yet foreign for a given patient fiber organization. We discovered that even significant variability of fiber organization had a relatively small effect on the spatio-temporal activation pattern during regular pacing. For a given pacing site, the activation maps were very similar across all fiber organizations tested.

Models of electrical excitation and recovery in the heart have become increasingly detailed, but have yet to be used routinely in the clinical setting to guide personalized intervention in patients. One of the main challenges is calibrating models from the limited measurements that can be made in a patient during a standard clinical procedure. In this work, we propose a novel framework for the probabilistic calibration of electrophysiology parameters on the left atrium of the heart using local measurements of cardiac excitability. Parameter fields are represented as Gaussian processes on manifolds and are linked to measurements via surrogate functions that map from local parameter values to measurements. The posterior distribution of parameter fields is then obtained. We show that our method can recover parameter fields used to generate localised synthetic measurements of effective refractory period. Our methodology is applicable to other measurement types collected with clinical protocols, and more generally for calibration where model parameters vary over a manifold., Comment: 14 pages, 6 figures, preprint

Coronary computed tomography angiography (CCTA) provides detailed an-atomical information on all chambers of the heart. Existing segmentation tools can label the gross anatomy, but addition of application-specific labels can require detailed and often manual refinement. We developed a U-Net based framework to i) extrapolate a new label from existing labels, and ii) parcellate one label into multiple labels, both using label-to-label mapping, to create a desired segmentation that could then be learnt directly from the image (image- to-label mapping). This approach only required manual correction in a small subset of cases (80 for extrapolation, 50 for parcella-tion, compared with 260 for initial labels). An initial 6-label segmentation (left ventricle, left ventricular myocardium, right ventricle, left atrium, right atrium and aorta) was refined to a 10-label segmentation that added a label for the pulmonary artery and divided the left atrium label into body, left and right veins and appendage components. The final method was tested using 30 cases, 10 each from Philips, Siemens and Toshiba scanners. In addition to the new labels, the median Dice scores were improved for all the initial 6 labels to be above 95% in the 10-label segmentation, e.g. from 91% to 97% for the left atrium body and from 92% to 96% for the right ventricle. This method provides a simple framework for flexible refinement of anatomical labels. The code and executables are available at cemrg.com., Comment: 9 pages, 5 figures, presented at Functional Imaging and Modeling of the Heart 2021

Computational Fluid Dynamics (CFD) is used to assist in designing artificial valves and planning procedures, focusing on local flow features. However, assessing the impact on overall cardiovascular function or predicting longer-term outcomes may require more comprehensive whole heart CFD models. Fitting such models to patient data requires numerous computationally expensive simulations, and depends on specific clinical measurements to constrain model parameters, hampering clinical adoption. Surrogate models can help to accelerate the fitting process while accounting for the added uncertainty. We create a validated patient-specific four-chamber heart CFD model based on the Navier-Stokes-Brinkman (NSB) equations and test Gaussian Process Emulators (GPEs) as a surrogate model for performing a variance-based global sensitivity analysis (GSA). GSA identified preload as the dominant driver of flow in both the right and left side of the heart, respectively. Left-right differences were seen in terms of vascular outflow resistances, with pulmonary artery resistance having a much larger impact on flow than aortic resistance. Our results suggest that GPEs can be used to identify parameters in personalized whole heart CFD models, and highlight the importance of accurate preload measurements., Comment: 8 pages plus 15 pages supplement, 6 figures, 3 tables, submitted to IEEE Transactions on Biomedical Engineering

Catheter ablation is currently the only curative treatment for scar-related ventricular tachycardias (VTs). However, not only are ablation procedures long, with relatively high risk, but success rates are punitively low, with frequent VT recurrence. Personalized in-silico approaches have the opportunity to address these limitations. However, state-of-the-art reaction diffusion (R-D) simulations of VT induction and subsequent circuits used for in-silico ablation target identification require long execution times, along with vast computational resources, which are incompatible with the clinical workflow. Here, we present the Virtual Induction and Treatment of Arrhythmias (VITA), a novel, rapid and fully automated computational approach that uses reaction-Eikonal methodology to induce VT and identify subsequent ablation targets. The rationale for VITA is based on finding isosurfaces associated with an activation wavefront that splits in the ventricles due to the presence of an isolated isthmus of conduction within the scar; once identified, each isthmus may be assessed for their vulnerability to sustain a reentrant circuit, and the corresponding exit site automatically identified for potential ablation targeting. VITA was tested on a virtual cohort of 7 post-infarcted porcine hearts and the results compared to R-D simulations. Using only a standard desktop machine, VITA could detect all scar-related VTs, simulating activation time maps and ECGs (for clinical comparison) as well as computing ablation targets in 48 minutes. The comparable VTs probed by the R-D simulations took 68.5 hours on 256 cores of high-performance computing infrastructure. The set of lesions computed by VITA was shown to render the ventricular model VT-free. VITA could be used in near real-time as a complementary modality aiding in clinical decision-making in the treatment of post-infarction VTs.

A variety of optimal control, estimation, system identification and design problems can be formulated as functional optimization problems with differential equality and inequality constraints. Since these problems are infinite-dimensional and often do not have a known analytical solution, one has to resort to numerical methods to compute an approximate solution. This paper uses a unifying notation to outline some of the techniques used in the transcription step of simultaneous direct methods (which discretize-then-optimize) for solving continuous-time dynamic optimization problems. We focus on collocation, integrated residual and Runge-Kutta schemes. These transcription methods are then applied to a simulation case study to answer a question that arose during the COVID-19 pandemic, namely: If there are not enough ventilators, is it possible to ventilate more than one patient on a single ventilator? The results suggest that it is possible, in principle, to estimate individual patient parameters sufficiently accurately, using a relatively small number of flow rate measurements, without needing to disconnect a patient from the system or needing more than one flow rate sensor. We also show that it is possible to ensure that two different patients can indeed receive their desired tidal volume, by modifying the resistance experienced by the air flow to each patient and controlling the ventilator pressure., Comment: Accepted to 59th IEEE Conference on Decision and Control, Jeju Island, Republic of Korea, December 14th-18th 2020

Simulating the interaction of fluids with immersed moving solids is playing an important role for gaining a better quantitative understanding of how fluid dynamics is altered by the presence of obstacles and which forces are exerted on the solids by the moving fluid. Such problems appear in various contexts, ranging from numerous technical applications such as turbines to medical problems such as the regulation of hemodyamics by valves. Typically, the numerical treatment of such problems is posed within a fluid structure interaction (FSI) framework. General FSI models are able to capture bidirectional interactions, but are challenging to solve and computationally expensive. Simplified methods offer a possible remedy by achieving better computational efficiency to broaden the scope to demanding application problems with focus on understanding the effect of solids on altering fluid dynamics. In this study we report on the development of a novel method for such applications. In our method rigid moving obstacles are incorporated in a fluid dynamics context using concepts from porous media theory. Based on the Navier-Stokes-Brinkman equations which augments the Navier-Stokes equation with a Darcy drag term our method represents solid obstacles as time-varying regions containing a porous medium of vanishing permeability. Numerical stabilization and turbulence modeling is dealt with by using a residual based variational multiscale formulation. The key advantages of our approach -- computational efficiency and ease of implementation -- are demonstrated by solving a standard benchmark problem of a rotating blood pump posed by the Food and Drug Administration Agency (FDA). Validity is demonstrated by conducting a mesh convergence study and by comparison against the extensive set of experimental data provided for this benchmark.

The use of heuristics to assess the convergence and compress the output of Markov chain Monte Carlo can be sub-optimal in terms of the empirical approximations that are produced. Typically a number of the initial states are attributed to "burn in" and removed, whilst the remainder of the chain is "thinned" if compression is also required. In this paper we consider the problem of retrospectively selecting a subset of states, of fixed cardinality, from the sample path such that the approximation provided by their empirical distribution is close to optimal. A novel method is proposed, based on greedy minimisation of a kernel Stein discrepancy, that is suitable for problems where heavy compression is required. Theoretical results guarantee consistency of the method and its effectiveness is demonstrated in the challenging context of parameter inference for ordinary differential equations. Software is available in the Stein Thinning package in Python, R and MATLAB., Comment: To appear in the Journal of the Royal Statistical Society, Series B, 2022+

In patients with atrial fibrillation, local activation time (LAT) maps are routinely used for characterising patient pathophysiology. The gradient of LAT maps can be used to calculate conduction velocity (CV), which directly relates to material conductivity and may provide an important measure of atrial substrate properties. Including uncertainty in CV calculations would help with interpreting the reliability of these measurements. Here, we build upon a recent insight into reduced-rank Gaussian processes (GP) to perform probabilistic interpolation of uncertain LAT directly on human atrial manifolds. Our Gaussian Process Manifold Interpolation (GPMI) method accounts for the topology of the atria, and allows for calculation of statistics for predicted CV. We demonstrate our method on two clinical cases, and perform validation against a simulated ground truth. CV uncertainty depends on data density, wave propagation direction, and CV magnitude. GPMI is suitable for probabilistic interpolation of other uncertain quantities on non-Euclidean manifolds.