A Framework for the Generation of Realistic Synthetic Cardiac Ultrasound and Magnetic Resonance Imaging Sequences From the Same Virtual Patients.

The use of synthetic sequences is one of the most promising tools for advanced in silico evaluation of the quantification of cardiac deformation and strain through 3-D ultrasound (US) and magnetic resonance (MR) imaging. In this paper, we propose the first simulation framework which allows the generation of realistic 3-D synthetic cardiac US and MR (both cine and tagging) image sequences from the same virtual patient. A state-of-the-art electromechanical (E/M) model was exploited for simulating groundtruth cardiac motion fields ranging from healthy to various pathological cases, including both ventricular dyssynchrony and myocardial ischemia. The E/M groundtruth along with template MR/US images and physical simulators were combined in a unified framework for generating synthetic data. We efficiently merged several warping strategies to keep the full control of myocardial deformations while preserving realistic image texture. In total, we generated 18 virtual patients, each with synthetic 3-D US, cine MR, and tagged MR sequences. The simulated images were evaluated both qualitatively by showing realistic textures and quantitatively by observing myocardial intensity distributions similar to real data. In particular, the US simulation showed a smoother myocardium/background interface than the state-of-the-art. We also assessed the mechanical properties. The pathological subjects were discriminated from the healthy ones by both global indexes (ejection fraction and the global circumferential strain) and regional strain curves. The synthetic database is comprehensive in terms of both pathology and modality, and has a level of realism sufficient for validation purposes. All the 90 sequences are made publicly available to the research community via an open-access database.

A Pipeline for the Generation of Realistic 3D Synthetic Echocardiographic Sequences: Methodology and Open-Access Database.

Quantification of cardiac deformation and strain with 3D ultrasound takes considerable research efforts. Nevertheless, a widespread use of these techniques in clinical practice is still held back due to the lack of a solid verification process to quantify and compare performance. In this context, the use of fully synthetic sequences has become an established tool for initial in silico evaluation. Nevertheless, the realism of existing simulation techniques is still too limited to represent reliable benchmarking data. Moreover, the fact that different centers typically make use of in-house developed simulation pipelines makes a fair comparison difficult. In this context, this paper introduces a novel pipeline for the generation of synthetic 3D cardiac ultrasound image sequences. State-of-the art solutions in the fields of electromechanical modeling and ultrasound simulation are combined within an original framework that exploits a real ultrasound recording to learn and simulate realistic speckle textures. The simulated images show typical artifacts that make motion tracking in ultrasound challenging. The ground-truth displacement field is available voxelwise and is fully controlled by the electromechanical model. By progressively modifying mechanical and ultrasound parameters, the sensitivity of 3D strain algorithms to pathology and image properties can be evaluated. The proposed pipeline is used to generate an initial library of 8 sequences including healthy and pathological cases, which is made freely accessible to the research community via our project web-page.

Improved myocardial motion estimation combining tissue Doppler and B-mode echocardiographic images.

We propose a technique for myocardial motion estimation based on image registration using both B-mode echocardiographic images and tissue Doppler sequences acquired interleaved. The velocity field is modeled continuously using B-splines and the spatiotemporal transform is constrained to be diffeomorphic. Images before scan conversion are used to improve the accuracy of the estimation. The similarity measure includes a model of the speckle pattern distribution of B-mode images. It also penalizes the disagreement between tissue Doppler velocities and the estimated velocity field. Registration accuracy is evaluated and compared to other alternatives using a realistic synthetic dataset, obtaining mean displacement errors of about 1 mm. Finally, the method is demonstrated on data acquired from six volunteers, both at rest and during exercise. Robustness is tested against low image quality and fast heart rates during exercise. Results show that our method provides a robust motion estimate in these situations.

Personalization of a cardiac electromechanical model using reduced order unscented Kalman filtering from regional volumes.

Patient-specific cardiac modeling can help in understanding pathophysiology and therapy planning. However it requires to combine functional and anatomical data in order to build accurate models and to personalize the model geometry, kinematics, electrophysiology and mechanics. Personalizing the electromechanical coupling from medical images is a challenging task. We use the Bestel-Clément-Sorine (BCS) electromechanical model of the heart, which provides reasonable accuracy with a reasonable number of parameters (14 for each ventricle) compared to the available clinical data at the organ level. We propose a personalization strategy from cine MRI data in two steps. We first estimate global parameters with an automatic calibration algorithm based on the Unscented Transform which allows to initialize the parameters while matching the volume and pressure curves. In a second step we locally personalize the contractilities of all AHA (American Heart Association) zones of the left ventricle using the reduced order unscented Kalman filtering on Regional Volumes. This personalization strategy was validated synthetically and tested successfully on eight healthy and three pathological cases.

Benchmarking framework for myocardial tracking and deformation algorithms: an open access database.

In this paper we present a benchmarking framework for the validation of cardiac motion analysis algorithms. The reported methods are the response to an open challenge that was issued to the medical imaging community through a MICCAI workshop. The database included magnetic resonance (MR) and 3D ultrasound (3DUS) datasets from a dynamic phantom and 15 healthy volunteers. Participants processed 3D tagged MR datasets (3DTAG), cine steady state free precession MR datasets (SSFP) and 3DUS datasets, amounting to 1158 image volumes. Ground-truth for motion tracking was based on 12 landmarks (4 walls at 3 ventricular levels). They were manually tracked by two observers in the 3DTAG data over the whole cardiac cycle, using an in-house application with 4D visualization capabilities. The median of the inter-observer variability was computed for the phantom dataset (0.77 mm) and for the volunteer datasets (0.84 mm). The ground-truth was registered to 3DUS coordinates using a point based similarity transform. Four institutions responded to the challenge by providing motion estimates for the data: Fraunhofer MEVIS (MEVIS), Bremen, Germany; Imperial College London - University College London (IUCL), UK; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Inria-Asclepios project (INRIA), France. Details on the implementation and evaluation of the four methodologies are presented in this manuscript. The manually tracked landmarks were used to evaluate tracking accuracy of all methodologies. For 3DTAG, median values were computed over all time frames for the phantom dataset (MEVIS=1.20mm, IUCL=0.73 mm, UPF=1.10mm, INRIA=1.09 mm) and for the volunteer datasets (MEVIS=1.33 mm, IUCL=1.52 mm, UPF=1.09 mm, INRIA=1.32 mm). For 3DUS, median values were computed at end diastole and end systole for the phantom dataset (MEVIS=4.40 mm, UPF=3.48 mm, INRIA=4.78 mm) and for the volunteer datasets (MEVIS=3.51 mm, UPF=3.71 mm, INRIA=4.07 mm). For SSFP, median values were computed at end diastole and end systole for the phantom dataset(UPF=6.18 mm, INRIA=3.93 mm) and for the volunteer datasets (UPF=3.09 mm, INRIA=4.78 mm). Finally, strain curves were generated and qualitatively compared. Good agreement was found between the different modalities and methodologies, except for radial strain that showed a high variability in cases of lower image quality.

3D strain assessment in ultrasound (Straus): a synthetic comparison of five tracking methodologies.

This paper evaluates five 3D ultrasound tracking algorithms regarding their ability to quantify abnormal deformation in timing or amplitude. A synthetic database of B-mode image sequences modeling healthy, ischemic and dyssynchrony cases was generated for that purpose. This database is made publicly available to the community. It combines recent advances in electromechanical and ultrasound modeling. For modeling heart mechanics, the Bestel-Clement-Sorine electromechanical model was applied to a realistic geometry. For ultrasound modeling, we applied a fast simulation technique to produce realistic images on a set of scatterers moving according to the electromechanical simulation result. Tracking and strain accuracies were computed and compared for all evaluated algorithms. For tracking, all methods were estimating myocardial displacements with an error below 1 mm on the ischemic sequences. The introduction of a dilated geometry was found to have a significant impact on accuracy. Regarding strain, all methods were able to recover timing differences between segments, as well as low strain values. On all cases, radial strain was found to have a low accuracy in comparison to longitudinal and circumferential components.

Preliminary specificity study of the Bestel-Clément-Sorine electromechanical model of the heart using parameter calibration from medical images.

Patient-specific cardiac modelling can help in understanding pathophysiology and predict therapy effects. This requires the personalization of the geometry, kinematics, electrophysiology and mechanics. We use the Bestel-Clément-Sorine (BCS) electromechanical model of the heart, which provides reasonable accuracy with a reduced parameter number compared to the available clinical data at the organ level. We propose a preliminary specificity study to determine the relevant global parameters able to differentiate the pathological cases from the healthy controls. To this end, a calibration algorithm on global measurements is developed. This calibration method was tested successfully on 6 volunteers and 2 heart failure cases and enabled to tune up to 7 out of the 14 necessary parameters of the BCS model, from the volume and pressure curves. This specificity study confirmed domain-knowledge that the relaxation rate is impaired in post-myocardial infarction heart failure and the myocardial stiffness is increased in dilated cardiomyopathy heart failures.

Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models.

This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection.

Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: a preliminary clinical validation.

Cardiac resynchronisation therapy (CRT) is an effective treatment for patients with congestive heart failure and a wide QRS complex. However, up to 30% of patients are non-responders to therapy in terms of exercise capacity or left ventricular reverse remodelling. A number of controversies still remain surrounding patient selection, targeted lead implantation and optimisation of this important treatment. The development of biophysical models to predict the response to CRT represents a potential strategy to address these issues. In this article, we present how the personalisation of an electromechanical model of the myocardium can predict the acute haemodynamic changes associated with CRT. In order to introduce such an approach as a clinical application, we needed to design models that can be individualised from images and electrophysiological mapping of the left ventricle. In this paper the personalisation of the anatomy, the electrophysiology, the kinematics and the mechanics are described. The acute effects of pacing on pressure development were predicted with the in silico model for several pacing conditions on two patients, achieving good agreement with invasive haemodynamic measurements: the mean error on dP/dt(max) is 47.5±35mmHgs(-1), less than 5% error. These promising results demonstrate the potential of physiological models personalised from images and electrophysiology signals to improve patient selection and plan CRT.

A statistical model for quantification and prediction of cardiac remodelling: application to tetralogy of Fallot.

Cardiac remodelling plays a crucial role in heart diseases. Analyzing how the heart grows and remodels over time can provide precious insights into pathological mechanisms, eventually resulting in quantitative metrics for disease evaluation and therapy planning. This study aims to quantify the regional impacts of valve regurgitation and heart growth upon the end-diastolic right ventricle (RV) in patients with tetralogy of Fallot, a severe congenital heart defect. The ultimate goal is to determine, among clinical variables, predictors for the RV shape from which a statistical model that predicts RV remodelling is built. Our approach relies on a forward model based on currents and a diffeomorphic surface registration algorithm to estimate an unbiased template. Local effects of RV regurgitation upon the RV shape were assessed with Principal Component Analysis (PCA) and cross-sectional multivariate design. A generative 3-D model of RV growth was then estimated using partial least squares (PLS) and canonical correlation analysis (CCA). Applied on a retrospective population of 49 patients, cross-effects between growth and pathology could be identified. Qualitatively, the statistical findings were found realistic by cardiologists. 10-fold cross-validation demonstrated a promising generalization and stability of the growth model. Compared to PCA regression, PLS was more compact, more precise and provided better predictions.

Inter-model consistency and complementarity: learning from ex-vivo imaging and electrophysiological data towards an integrated understanding of cardiac physiology.

Computational models of the heart at various scales and levels of complexity have been independently developed, parameterised and validated using a wide range of experimental data for over four decades. However, despite remarkable progress, the lack of coordinated efforts to compare and combine these computational models has limited their impact on the numerous open questions in cardiac physiology. To address this issue, a comprehensive dataset has previously been made available to the community that contains the cardiac anatomy and fibre orientations from magnetic resonance imaging as well as epicardial transmembrane potentials from optical mapping measured on a perfused ex-vivo porcine heart. This data was used to develop and customize four models of cardiac electrophysiology with different level of details, including a personalized fast conduction Purkinje system, a maximum a posteriori estimation of the 3D distribution of transmembrane potential, the personalization of a simplified reaction-diffusion model, and a detailed biophysical model with generic conduction parameters. This study proposes the integration of these four models into a single modelling and simulation pipeline, after analyzing their common features and discrepancies. The proposed integrated pipeline demonstrates an increase prediction power of depolarization isochrones in different pacing conditions.

Coupled personalisation of electrophysiology models for simulation of induced ischemic ventricular tachycardia.

Despite recent efforts in cardiac electrophysiology modelling, there is still a strong need to make macroscopic models usable in planning and assistance of the clinical procedures. This requires model personalisation i.e. estimation of patient-specific model parameters and computations compatible with clinical constraints. Fast macroscopic models allow a quick estimation of the tissue conductivity, but are often unreliable in prediction of arrhythmias. On the other side, complex biophysical models are quite expensive for the tissue conductivity estimation, but are well suited for arrhythmia predictions. Here we present a coupled personalisation framework, which combines the benefits of the two models. A fast Eikonal (EK) model is used to estimate the conductivity parameters, which are then used to set the parameters of a biophysical model, the Mitchell-Schaeffer (MS) model. Additional parameters related to Action Potential Duration (APD) and APD restitution curves for the tissue are estimated for the MS model. This framework is applied to a clinical dataset provided with an hybrid X-Ray/MR imaging on an ischemic patient. This personalised MS Model is then used for in silico simulation of clinical Ventricular Tachycardia (VT) stimulation protocol to predict the induction of VT. This proof of concept opens up possibilities of using VT induction modelling directly in the intervention room, in order to plan the radio-frequency ablation lines.

LogDemons revisited: consistent regularisation and incompressibility constraint for soft tissue tracking in medical images.

Non-linear image registration is a standard approach to track soft tissues in medical images. By estimating spatial transformations between images, visible structures can be followed over time. For clinical applications the model of transformation must be consistent with the properties of the biological tissue, such as incompressibility. LogDemons is a fast non-linear registration algorithm that provides diffusion-like diffeomorphic transformations parameterised by stationary velocity fields. Yet, its use for tissue tracking has been limited because of the ad-hoc Gaussian regularisation that prevents implementing other transformation models. In this paper, we propose a mathematical formulation of demons regularisation that fits into LogDemons framework. This formulation enables to ensure volume-preserving deformations by minimising the energy functional directly under the linear divergence-free constraint, yielding little computational overhead. Tests on synthetic incompressible fields showed that our approach outperforms the original logDemons in terms of incompressible deformation recovery. The algorithm showed promising results on one patient for the automatic recovery of myocardium strain from cardiac anatomical and 3D tagged MRI.

Cardiac electrophysiology model adjustment using the fusion of MR and optical imaging.

Despite important recent efforts in cardiac electrophysiology modelling, there is still a strong need for validating macroscopic models, that are well suited for diagnosis and treatment planning. In this paper we present a method to adjust the parameters of a macroscopic electrophysiology model on depolarisation and repolarisation maps obtained ex-vivo from optical imaging. With this imaging technique, optical fluorescence data are recorded with high spatial and temporal resolution on a large healthy porcine heart. A model of the myocardium is built from the MR images of the same heart, which also integrates the myocardial fibre orientation measured with DTI. We then present the first quantitative adjustment of a personalised volumetric model of the myocardium.

Anisotropic wave propagation and apparent conductivity estimation in a fast electrophysiological model: application to XMR interventional imaging.

Cardiac arrhythmias are increasingly being treated using ablation procedures. Development of fast electrophysiological models and estimation of parameters related to conduction pathologies can aid in the investigation of better treatment strategies during Radio-frequency ablations. We present a fast electrophysiological model incorporating anisotropy of the cardiac tissue. A global-local estimation procedure is also outlined to estimate a hidden parameter (apparent electrical conductivity) present in the model. The proposed model is tested on synthetic and real data derived using XMR imaging. We demonstrate a qualitative match between the estimated conductivity parameter and possible pathology locations. This approach opens up possibilities to directly integrate modelling in the intervention room.

Cardiac function estimation from MRI using a heart model and data assimilation: advances and difficulties.

In this paper, we present a framework to estimate local ventricular myocardium contractility using clinical MRI, a heart model and data assimilation. First, we build a generic anatomical model of the ventricles including muscle fibre orientations and anatomical subdivisions. Then, this model is deformed to fit a clinical MRI, using a semi-automatic fuzzy segmentation, an affine registration method and a local deformable biomechanical model. An electromechanical model of the heart is then presented and simulated. Finally, a data assimilation procedure is described, and applied to this model. Data assimilation makes it possible to estimate local contractility from given displacements. Presented results on fitting to patient-specific anatomy and assimilation with simulated data are very promising. Current work on model calibration and estimation of patient parameters opens up possibilities to apply this framework in a clinical environment.

An electromechanical model of the heart for image analysis and simulation.

This paper presents a new three-dimensional electromechanical model of the two cardiac ventricles designed both for the simulation of their electrical and mechanical activity, and for the segmentation of time series of medical images. First, we present the volumetric biomechanical models built. Then the transmembrane potential propagation is simulated, based on FitzHugh-Nagumo reaction-diffusion equations. The myocardium contraction is modeled through a constitutive law including an electromechanical coupling. Simulation of a cardiac cycle, with boundary conditions representing blood pressure and volume constraints, leads to the correct estimation of global and local parameters of the cardiac function. This model enables the introduction of pathologies and the simulation of electrophysiology interventions. Moreover, it can be used for cardiac image analysis. A new proactive deformable model of the heart is introduced to segment the two ventricles in time series of cardiac images. Preliminary results indicate that this proactive model, which integrates a priori knowledge on the cardiac anatomy and on its dynamical behavior, can improve the accuracy and robustness of the extraction of functional parameters from cardiac images even in the presence of noisy or sparse data. Such a model also allows the simulation of cardiovascular pathologies in order to test therapy strategies and to plan interventions.

Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging.

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and for therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between X-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium using XMR imaging. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patient data. Pathologies are introduced in the model and simulations are compared to measured data. Initial qualitative comparison on the two clinical cases presented is encouraging. Once fully validated, these models will make it possible to simulate different interventional strategies.

Localization of abnormal conduction pathways for tachyarrhythmia treatment using tagged MRI.

Tachyarrhythmias are pathological fast heart rhythms often caused by abnormally conducting myocardial areas (foci). Treatment by radio-frequency (RF) ablation uses electrode-catheters to monitor and destroy foci. The procedure is normally guided with x-rays (2D), and thus prone to errors in location and excessive radiation exposure. Our main goal is to provide pre- and intra-operative 3D MR guidance in XMR systems by locating the abnormal conduction pathways. We address the inverse electro-mechanical relation by using motion in order to infer electrical propagation. For this purpose we define a probabilistic measure of the onset of regional myocardial activation, derived from 3D motion fields obtained by tracking tagged MR sequences with non-rigid registration. Activation isochrones are then derived to determine activation onset. We also compare regional motion between two different image acquisitions, thus assisting in diagnosing arrhythmia, in follow up of treatment, and in determining whether the ablation was successful. Difference maps of isochrones and other motion descriptors are computed to determine abnormal patterns. Validation was carried out using an electromechanical model of the heart, synthetic data, a cardiac MRI atlas of motion and geometry, MRI data from 6 healthy volunteers (one of them subjected to stress), and an MRI study on a patient with tachyarrhythmia, before and after RF ablation. A pre-operative MRI study on a second patient with tachyarrhythmia was used to test the methodology in a clinical scenario, predicting the abnormally conducting region.