Septal Flash Assessment on CRT Candidates Based on Statistical Atlases of Motion

International audienceIn this paper, we propose a complete framework for the automatic detection and quantification of abnormal heart motion patterns using Statistical Atlases of Motion built from healthy populations. The method is illustrated on CRT patients with identified cardiac dyssyn-chrony and abnormal septal motion on 2D ultrasound (US) sequences. The use of the 2D US modality guarantees that the temporal resolution of the image sequences is high enough to work under a small displacements hypothesis. Under this assumption, the computed displacement fields can be directly considered as cardiac velocities. Comparison of subjects acquired with different spatiotemporal resolutions implies the reorientation and temporal normalization of velocity fields in a common space of coordinates. Statistics are then performed on the reoriented vector fields. Results show the ability of the method to correctly detect abnormal motion patterns and quantify their distance to normality. The use of local p-values for quantifying abnormal motion patterns is believed to be a promising strategy for computing new markers of cardiac dyssynchrony for better characterizing CRT candidates

Atlas-Based Quantification of Myocardial Motion Abnormalities: Added-Value for Understanding the Effect of Cardiac Resynchronization Therapy

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A spatiotemporal statistical atlas of motion for the quantification of abnormal myocardial tissue velocities

International audienceIn this paper, we present a new method for the automatic comparison of myocardial motion patterns and the characterization of their degree of abnormality, based on a statistical atlas of motion built from a reference healthy population. Our main contribution is the computation of atlas-based indexes that quantify the abnormality in the motion of a given subject against a reference population, at every location in time and space. The critical computational cost inherent to the construction of an atlas is highly reduced by the definition of myocardial velocities under a small displacements hypothesis. The indexes we propose are of notable interest for the assessment of anomalies in cardiac mobility and synchronicity when applied, for instance, to candidate selection for cardiac resynchronization therapy (CRT). We built an atlas of normality using 2D ultrasound cardiac sequences from 21 healthy volunteers, to which we compared 14 CRT patients with left ventricular dyssynchrony (LVDYS). We illustrate the potential of our approach in characterizing septal flash, a specific motion pattern related to LVDYS and recently introduced as a very good predictor of response to CRT

Atlas-based Quantification of Myocardial Motion Abnormalities: Added-value for the Understanding of CRT Outcome?

International audienceIn this paper, we present the use of atlas-based indexes of abnormality for the quantification of cardiac resynchronization therapy (CRT) outcome in terms of motion. We build an atlas of normal motion from 21 healthy volunteers to which we compare 88 CRT candidates before and after the therapy. Abnormal motion is quantified locally in time and space using a statistical distance to normality, and changes induced by the therapy are related with clinical measurements of CRT outcome. Results correlate with recent clinical hypothesis about CRT response, namely that the correction of specific mechanisms responsible for cardiac dyssynchrony conditions the response to the therapy

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

Constrained manifold learning for the characterization of pathological deviations from normality

International audienceThis paper describes a technique to (1) learn the representation of a pathological motion pattern from a given population, and (2) compare individuals to this population. Our hypothesis is that this pattern can be modeled as a deviation from normal motion by means of non-linear embedding techniques. Each subject is represented by a 2D map of local motion abnormalities, obtained from a statistical atlas of myocardial motion built from a healthy population. The algorithm estimates a manifold from a set of patients with varying degrees of the same disease, and compares individuals to the training population using a mapping to the manifold and a distance to normality along the manifold. The approach extends recent manifold learning techniques by constraining the manifold to pass by a physiologically meaningful origin representing a normal motion pattern. Interpolation techniques using locally adjustable kernel improve the accuracy of the method. The technique is applied in the context of cardiac resynchronization therapy (CRT), focusing on a specific motion pattern of intra-ventricular dyssynchrony called septal flash (SF). We estimate the manifold from 50 CRT candidates with SF and test it on 37 CRT candidates and 21 healthy volunteers. Experiments highlight the relevance of nonlinear techniques to model a pathological pattern from the training set and compare new individuals to this pattern

A groupwise mutual information metric for cost efficient selection of a suitable reference in cardiac computational atlas construction

International audienceComputational atlases based on nonrigid registration have found much use in the medical imaging community. To avoid bias to any single element of the training set, there are two main approaches: using a (random) subject to serve as an initial reference and posteriorly removing bias, and a true groupwise registration with a constraint of zero average transformation for direct computation of the atlas. Major drawbacks are the possible selection of an outlier on one side, and an initialization with an invalid instance on the other. In both cases there is great potential for affecting registration performance, and producing a final average image in which the structure of interest deviates from the central anatomy of the population under study. We propose an inexpensive means of reference selection based on a groupwise correspondence measure, which avoids the selection of an outlier and is independent from the atlas construction approach that follows. Thus, it improves tractability of reference selection and robustness of automated atlas construction. We illustrate the method using a set of 20 cardiac multislice computed tomography volumes

Early Detection of Doxorubicin-Induced Cardiotoxicity Using Combined Biomechanical Modeling and Multi-Parametric Cardiovascular MRI

RÉSUMÉ La chimiothérapie à la doxorubicine est efficace et est largement utilisée pour traiter la leucémie lymphoblastique aiguë. Toutefois, son efficacité est entravée par un large spectre de cardiotoxicités incluant des changements affectant à la fois la morphologie et la fonction du myocarde. Ces changements dépendent principalement de la dose cumulée administrée au patient. Actuellement, très peu de techniques sont disponibles pour détecter de telles cardiotoxicités. L'utilisation d’images de fibres musculaires (par exemple, à l’aide de l’imagerie des tenseurs de diffusion par IRM) ou des techniques d'imagerie 3D (par exemple, ciné DENSE IRM) sont des alternatives prometteuses, cependant, leur application en clinique est limitée en raison du temps d'acquisition d’images et les erreurs d'estimation qui en résultent. En revanche, l'utilisation de l'IRM multi-paramétrique ainsi que le ciné IRM sont des alternatives prometteuses, puisque ces techniques sont déjà disponibles au niveau clinique. L’IRM multiparamétrique incluant l’imagerie des temps de relaxation T1 et T2 peut être utile dans la détection des lésions dans le tissu du myocarde alors que l’imagerie ciné IRM peut être plus appropriée pour détecter les changements fonctionnels au sein du myocarde. La combinaison de ces deux techniques peut également permettre une caractérisation complète de la fonction du tissu myocardique. Dans ce projet, l'utilisation des temps de relaxation T1 pré- et post-gadolinium et T2 est d'abord évaluée et proposée pour détecter les dommages myocardiques induits par la chimiothérapie à la doxorubicine. En second lieu, l'utilisation de patrons 2D de déplacements myocardiques est évaluée dans le cadre de la détection des dommages myocardiques et altération fonctionnelle due au traitement à la doxorubicine. Enfin, l'utilisation de la modélisation par éléments finis, incluant les contraintes et déformations mécaniques est proposée pour évaluer les changements dans les propriétés mécaniques au niveau du myocarde, avec l’hypothèse que le traitement à base de doxorubicine induit des changements importants à la fois dans le tissu et au niveau de la fonction myocardique. Dans notre cohorte de survivants de cancer, des changements myocardiques locaux ont été trouvés entre le groupe à risque standard et le groupe à risque élevé lorsque le T1 pré-gadolinium fut utilisé. Ces changements ont été amplifiés avec l’utilisation d’agent de contraste tel que confirmé par le coefficient de partition, ce qui suggère que l’utilisation du T1 post-gadolonium et le coefficient de----------ABSTRACT Doxorubicin chemotherapy is effective and widely used to treat acute lymphoblastic leukemia. However, its effectiveness is hampered by a wide spectrum of dose-dependent cardiotoxicity including both morphological and functional changes affecting the myocardium. Currently, very few techniques are available for detecting such cardiotoxic effect. The use of muscle fibers orientation (e.g., diffusion tensor imaging DT-MRI) or 3D imaging techniques (e.g., cine DENSE MRI) are possible alternatives, however, their clinical application is limited due to the acquisition time and their estimation errors. In contrast, the use of multi-parametric MRI along with cine MRI is a promising alternative, since theses techniques are already available at a clinical level. Multiparametric MRI including T1 and T2 imaging may be helpful in detecting myocardial tissue damage, while cine MRI may be more appropriate to detect functional changes within the myocardium. The combination of these two techniques may further allow an extensive characterization of myocardial tissue function. In this doctoral project, the use of pre- and post-gadolinium T1 and T2 relaxation times is firstly assessed and proposed to detect myocardial damage induced by doxorubicin chemotherapy. Secondly, the use of 2D myocardial displacement patterns is assessed in detecting myocardial damage and functional alteration due to doxorubicin-based treatment. Finally, the use of finite element modeling including mechanical strains and stresses to evaluate mechanical properties changes within the myocardium is alternatively proposed, assuming that doxorubicin-based treatment induces significant changes to both myocardial tissue morphology and function. In our cohort of cancer survivors, local myocardial changes were found between standard risk and high risks group using pre-gadolinium T1 relaxation times. These changes were further amplified with gadolinium enhancement, as confirmed by the use of partition coefficient, suggesting this MRI parameter along with partition coefficient as candidates imaging markers of doxorubicin induced cardiomyopathy. The use of T2 on the other hand showed that the high risk group of cancer survivors had higher T2 relaxation times compared to the standard risk group and similar to reported values. Though, a larger cohort of cancer survivors may be required to assess the use of T1 and T2 relaxation time as possible indices for myocardial tissue damage in the onset of doxorubicin-induced cardiotoxicity

Cardiac MRI in the evaluation of Acute Cardiac Toxicity following Cancer Therapy, with a focus on Radiation

Studies have shown that radiation related cardiac toxicity, initially thought to be a late phenomena, may have an acute impact on the heart. Understanding of functional and anatomical changes occurring in acute radiation cardiac toxicity is limited. Several studies have demonstrated sonographically derived reduction in myocardial strain following radiation with some studies suggesting a correlation between strain reduction and radiation dose. Cardiac MRI is a novel imaging modality in oncology. The aims of this study were to characterise the acute toxicities of radiation treatment and correlate these changes with radiation dose. A feasibility trial using cardiac MRI was performed with recruitment of a mixed cohort of cancer patients; breast cancer, thoracic malignancies and in haematological patients. Cardiac MRIs were performed at baseline prior to treatment, with additional imaging performed 6-8 following each treatment, before a final 12 months post treatment scan in order to determine changes in myocardial tissue (myocardial mapping) and myocardial function (strain). Doses were determined to cardiac substructures as individual segments of the left ventricle which were then correlated with these imaging changes to determine the absence or presence of a dose response relationship. This study resulted in the development of a novel contouring technique which has enabled more precise dosimetry to the cardiac substructures, including individual segments of the left ventricle. In the setting of breast cancer cardiac MRI has detected subtle ventricular changes which are suggestive of subacute myocardial inflammation and oedema. No changes were however noted in myocardial strain potentially suggesting the inferiority of cardiac MRI when compared to echocardiography in detecting strain abnormalities. A dose response relationship was seen between radiation strain and myocardial tissue changes. Recruitment of haematological and thoracic cancer patients into this study with a high imaging burden has proved challenging. This study adds to the body of evidence surrounding acute myocardial changes following radiation therapy. This study has allowed more accurate delineation of radiation dose to cardiac substructures and segments of the left ventricle. Cardiac MRI is a novel technique in the setting of acute radiation cardiotoxicity and may show promise in detecting acute tissue changes in breast cancer, however this warrants further study

Design and clinical validation of novel imaging strategies for analysis of arrhythmogenic substrate

_CURRENT CHALLENGES IN ELECTROPHYSIOLOGY_ Technical advances in cardiovascular electrophysiology have resulted in an increasing number of catheter ablation procedures reaching 200 000 in Europe for the year 2013. These advanced interventions are often complex and time consuming and may cause significant radiation exposure. Furthermore, a substantial number of ablation procedures remain associated with poor (initial) outcomes and frequently require ≥1 redo procedures. Innovations in modalities for substrate imaging could facilitate our understanding of the arrhythmogenic substrate, improve the design of patient-specific ablation strategies and improve the results of ablation procedures. _NOVEL SUBSTRATE IMAGING MODALITIES_ __Cardiac magnetic resonance__ Cardiac magnetic resonance imaging (CMR) can be considered the most comprehensive and suitable modality for the complete electrophysiology and catheter ablation workup (including patient selection, procedural guidance, and [procedural] follow-up). Utilizing inversion recovery CMR, fibrotic myocardium can be visualized and quantified 10–15 min after intravenous administration of Gadolinium contrast. This imaging technique is known as late Gadolinium enhancement (LGE) imaging. Experimental models have shown excellent agreement between size and shape in LGE CMR and areas of myocardial infarction by histopathology. Recent studies have also demonstrated how scar size, shape and location from pre-procedural LGE can be useful in guiding ventricular tachycardia’s (VT) ablation or atrial fibrillation (AF) ablation. These procedures are often time-consuming due to the preceding electrophysiological mapping study required to identify slow conduction zones involved in re-entry circuits. Post-processed LGE images provide scar maps, which could be integrated with electroanatomic mapping systems to facilitate these procedures. __Inverse potential mapping__ Through the years, various noninvasive electrocardiographic imaging techniques have emerged that estimate epicardial potentials or myocardial activation times from potentials recorded on the thorax. Utilizing an inverse procedure, the potentials on the heart surface or activation times of the myocardium are estimated with the recorded body surface potentials as source data. Although this procedure only estimates the time course of unipolar epicardial electrograms, several studies have demonstrated that the epicardial potentials and electrograms provide substantial information about intramyocardial activity and have great potential to facilitate risk-stratification and generate personalized ablation strategies. __Objectives of this thesis__ 1. To evaluate the utility of cardiac magnetic resonance derived geometrical and tissue characteristic information for patient stratification and guidance of AF ablation. 2. To design and evaluate the performance of a finite element model based inverse potential mapping in predicting the arrhythmogenic focus in idiopathic ventricular tachycardia using invasive electro-anatomical activation mapping as a reference standard