Advances in computational modelling for personalised medicine after myocardial infarction

Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners

A patient-specific echogenic soft robotic left ventricle embedded into a closed-loop cardiovascular simulator for advanced device testing

Cardiovascular medical devices undergo a large number of pre- and post-market tests before their approval for clinical practice use. Sophisticated cardiovascular simulators can significantly expedite the evaluation process by providing a safe and controlled environment and representing clinically relevant case scenarios. The complex nature of the cardiovascular system affected by severe pathologies and the inherently intricate patient-device interaction creates a need for high-fidelity test benches able to reproduce intra- and inter-patient variability of disease states. Therefore, we propose an innovative cardiovascular simulator that combines in silico and in vitro modeling techniques with a soft robotic left ventricle. The simulator leverages patient-specific and echogenic soft robotic phantoms used to recreate the intracardiac pressure and volume waveforms, combined with an in silico lumped parameter model of the remaining cardiovascular system. Three different patient-specific profiles were recreated, to assess the capability of the simulator to represent a variety of working conditions and mechanical properties of the left ventricle. The simulator is shown to provide a realistic physiological and anatomical representation thanks to the use of soft robotics combined with in silico modeling. This tool proves valuable for optimizing and validating medical devices and delineating specific indications and boundary conditions.</p

Apprentissage statistique pour la personnalisation de modèles cardiaques à partir de données d’imagerie

This thesis focuses on the calibration of an electromechanical model of the heart from patient-specific, image-based data; and on the related task of extracting the cardiac motion from 4D images. Long-term perspectives for personalized computer simulation of the cardiac function include aid to the diagnosis, aid to the planning of therapy and prevention of risks. To this end, we explore tools and possibilities offered by statistical learning. To personalize cardiac mechanics, we introduce an efficient framework coupling machine learning and an original statistical representation of shape & motion based on 3D+t currents. The method relies on a reduced mapping between the space of mechanical parameters and the space of cardiac motion. The second focus of the thesis is on cardiac motion tracking, a key processing step in the calibration pipeline, with an emphasis on quantification of uncertainty. We develop a generic sparse Bayesian model of image registration with three main contributions: an extended image similarity term, the automated tuning of registration parameters and uncertainty quantification. We propose an approximate inference scheme that is tractable on 4D clinical data. Finally, we wish to evaluate the quality of uncertainty estimates returned by the approximate inference scheme. We compare the predictions of the approximate scheme with those of an inference scheme developed on the grounds of reversible jump MCMC. We provide more insight into the theoretical properties of the sparse structured Bayesian model and into the empirical behaviour of both inference schemesCette thèse porte sur un problème de calibration d'un modèle électromécanique de cœur, personnalisé à partir de données d'imagerie médicale 3D+t ; et sur celui - en amont - de suivi du mouvement cardiaque. A cette fin, nous adoptons une méthodologie fondée sur l'apprentissage statistique. Pour la calibration du modèle mécanique, nous introduisons une méthode efficace mêlant apprentissage automatique et une description statistique originale du mouvement cardiaque utilisant la représentation des courants 3D+t. Notre approche repose sur la construction d'un modèle statistique réduit reliant l'espace des paramètres mécaniques à celui du mouvement cardiaque. L'extraction du mouvement à partir d'images médicales avec quantification d'incertitude apparaît essentielle pour cette calibration, et constitue l'objet de la seconde partie de cette thèse. Plus généralement, nous développons un modèle bayésien parcimonieux pour le problème de recalage d'images médicales. Notre contribution est triple et porte sur un modèle étendu de similarité entre images, sur l'ajustement automatique des paramètres du recalage et sur la quantification de l'incertitude. Nous proposons une technique rapide d'inférence gloutonne, applicable à des données cliniques 4D. Enfin, nous nous intéressons de plus près à la qualité des estimations d'incertitude fournies par le modèle. Nous comparons les prédictions du schéma d'inférence gloutonne avec celles données par une procédure d'inférence fidèle au modèle, que nous développons sur la base de techniques MCMC. Nous approfondissons les propriétés théoriques et empiriques du modèle bayésien parcimonieux et des deux schémas d'inférenc

Atlas construction and image analysis using statistical cardiac models

International audienceThis paper presents a brief overview of current trends in the construction of population and multi-modal heart atlases in our group and their application to atlas-based cardiac image analysis. The technical challenges around the construction of these atlases are organized around two main axes: groupwise image registration of anatomical, motion and fiber images and construction of statistical shape models. Application-wise, this paper focuses on the extraction of atlas-based biomarkers for the detection of local shape or motion abnormalities, addressing several cardiac applications where the extracted information is used to study and grade different pathologies. The paper is concluded with a discussion about the role of statistical atlases in the integration of multiple information sources and the potential this can bring to in-silico simulations

Guest Editorial Special Issue on Medical Imaging and Image Computing in Computational Physiology

International audienceThe January 2013 Special Issue of IEEE transactions on medical imaging discusses papers on medical imaging and image computing in computational physiology. Aslanid and co-researchers present an experimental technique based on stained micro computed tomography (CT) images to construct very detailed atrial models of the canine heart. The paper by Sebastian proposes a model of the cardiac conduction system (CCS) based on structural information derived from stained calf tissue. Ho, Mithraratne and Hunter present a numerical simulation of detailed cerebral venous flow. The third category of papers deals with computational methods for simulating medical imagery and incorporate knowledge of imaging physics and physiology/biophysics. The work by Morales showed how the combination of device modeling and virtual deployment, in addition to patient-specific image-based anatomical modeling, can help to carry out patient-specific treatment plans and assess alternative therapeutic strategies