Analysis of cardiac motion using MRI and nonrigid image registration

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Four-dimensional cardiac imaging in living embryos via postacquisition synchronization of nongated slice sequences

Being able to acquire, visualize, and analyze 3D time series (4D data) from living embryos makes it possible to understand complex dynamic movements at early stages of embryonic development. Despite recent technological breakthroughs in 2D dynamic imaging, confocal microscopes remain quite slow at capturing optical sections at successive depths. However, when the studied motion is periodic— such as for a beating heart—a way to circumvent this problem is to acquire, successively, sets of 2D+time slice sequences at increasing depths over at least one time period and later rearrange them to recover a 3D+time sequence. In other imaging modalities at macroscopic scales, external gating signals, e.g., an electro-cardiogram, have been used to achieve proper synchronization. Since gating signals are either unavailable or cumbersome to acquire in microscopic organisms, we have developed a procedure to reconstruct volumes based solely on the information contained in the image sequences. The central part of the algorithm is a least-squares minimization of an objective criterion that depends on the similarity between the data from neighboring depths. Owing to a wavelet-based multiresolution approach, our method is robust to common confocal microscopy artifacts. We validate the procedure on both simulated data and in vivo measurements from living zebrafish embryos

Quantification of ventricular mechanical dyssynchrony under stress

L'évaluation de l'asynchronisme mécanique ventriculaire sous stress a soulevé une attention importante en tant que facteur prédictif de la réponse au traitement de resynchronisation cardiaque (CRT). De plus, il semble exister une relation significative entre le devenir du patient et la présence d’asynchronisme au repos. Plusieurs méthodes échocardiographiques peuvent être utilisées pour évaluer l’asynchronisme. Cependant, parmi toutes les différentes méthodologies ou index existant dans ce domaine, aucun critère ne fait l’unanimité. Cette thèse étudie l'importance des techniques d'imagerie nucléaire dans le cadre de l’évaluation de l’asynchronisme cardiaque induit par le stress en utilisant trois différents modèles canins expérimentaux. Le premier chapitre vise à examiner les effets du stress sur le synchronisme de la contraction du ventricule gauche (VG) en utilisant l'imagerie synchronisée de perfusion myocardique dans une cohorte canine normale. Le stress a été induit par différents niveaux d’infusion de dobutamine sur six sujets sains. Les paramètres hémodynamiques et l’asynchronisme ont été évalués par des mesures de pressions ventriculaires. L'analyse de phase sur l’imagerie s’est effectuée en utilisant un logiciel commercialement disponible (QGS) et un logiciel interne (MHI4MPI), basée sur le déplacement et l’épaississement des parois ventriculaires. L’augmentation de la concentration de dobutamine a démontré une amélioration de la capacité fonctionnelle et une réduction de l’asynchronisme ventriculaire. L’analyse de l’asynchronisme calculée à partir de l’épaississement de la paroi semble plus robuste et plus sensible que l’utilisation du déplacement des parois. (Salimian et. al., J Nucl Cardiol., 2014) Le second chapitre étudie les différents paramètres d’asynchronisme au repos et à différents niveaux de stress dans un modèle de cardiomyopathie dilatée et à QRS étroit. Ce modèle a été créé sur dix chiens par tachycardie via stimulation de l'apex du ventricule droit pendant 3-4 semaines, permettant d’atteindre une fraction d'éjection cible de 35% ou moins. Le stress a ensuite été induit par une perfusion de dobutamine jusqu'à un maximum de 20 μg/kg/min. Les données hémodynamiques et l’asynchronisme ont été analysés par des mesures de pression ventriculaire et l’analyse de l’imagerie dynamique du compartiment sanguin. L’importante variabilité individuelle des sujets inclus dans notre cohorte empêche toute conclusion définitive sur la mesure de l’asynchronisme interventriculaire. Cependant, les différents niveaux de stress, même dans des intervalles rapprochés, ont démontré un effet significatif sur les paramètres hémodynamiques et l’asynchronisme. (Salimian et. al., J Nucl Cardiol., 2015) La troisième section vise à déterminer si l’estimation du mode de stimulation optimal effectuée au repos demeure le choix optimal lorsque le niveau d’activité cardiaque s’intensifie pour des sujets avec bloc auriculo-ventriculaire (AV) et fonction ventriculaire normale. Cinq chiens ont été soumis à une ablation du nœud AV et des sondes de stimulation ont été insérées dans l'oreillette droite pour la détection, l’apex du ventricule droit (VD) et une veine postérolatérale du VG pour la stimulation. Cinq modes de stimulation ont été utilisés : LV pur, biventriculaire (BiV) avec pré-activation de 20 ms du LV (LVRV20), BiV pur, BiV avec pré-activation de 20 ms du VD (RVLV20), VD pur. Des niveaux jusqu’à 20 μg/kg/min de dobutamine ont été atteints. Le stress a modifié l’étendue de l’asynchronisme de base et ce, pour tous les modes de stimulation. De plus, les effets physiologiques intrinsèques du stress permettent une évaluation plus précise de l’asynchronisme ventriculaire, diminuant la variabilité inter-sujet. Le mode de stimulation LVRV20 semble le mode optimal dans ce modèle, supportant l’utilisation de la stimulation bi-ventriculaire.Assessment of ventricular mechanical dyssynchrony (MD) under stress has attracted a large amount of attention as a stronger predictor of response to cardiac resynchronization therapy (CRT) and as a parameter whose variation bears a greater relationship to clinical outcomes than resting-MD either in CRT candidates or another subset of patients. Several echocardiographic methods can be used to assess stress-MD. However, no standardized approach is currently used to explore stress-induced variations in inter- and intraventricular MD. This dissertation studies the importance of nuclear imaging techniques in assessing stress-induced MD variations by providing three different experimental canine models. The first chapter sought to examine the impacts of stress on the left ventricular (LV) synchrony with phase analysis of gated SPECT myocardial perfusion imaging (GMPS) within a normal canine cohort. Stress was induced by different levels of dobutamine infusion in six healthy subjects. Hemodynamic and LV MD parameters were assessed by LV pressure measurements and phase analysis of GMPS using commercially available QGS software and in-house MHI4MPI software with thickening- and displacement-based methodology. The increase of dobutamine level was shown to be in accordance with the improvement of LV functional capacity and reduction of MD parameters. MD analysis based on wall thickening was more robust and sensitive than the global wall displacement. (Salimian et. al., J Nucl Cardiol., 2014) The second chapter investigated the range of difference in inter- and intraventricular MD parameters from rest to various levels of stress in a dilated cardiomyopathy (DCM) and narrow QRS complex model. Ten large dogs were submitted to tachycardia-induced DCM by pacing the right ventricular apex for 3-4 weeks to reach a target ejection fraction of 35% or less. Stress was then induced by infusion of dobutamine up to a maximum of 20 μg/kg/min. Hemodynamic and MD data were analyzed by LV pressure measurements and gated-blood pool SPECT (GBPS) imaging. Individual differences in the magnitude and pattern of change in the various levels of stress precluded any definitive conclusion about interventricular MD. However, different levels of stress, even in close intervals, showed a significant positive impact on hemodynamic and intraventricular MD parameters. (Salimian et. al., J Nucl Cardiol., 2015) The third chapter sought to examine if the optimal pacing mode at rest could be the best one during the maximum stress level in terms of MD parameters in subjects with an atrioventricular (AV) block and normal function. Five dogs were submitted to AV node ablation and pacing leads were placed in the right atrium for sensing, in right ventricular (RV) apex, and in posterolateral LV vein for pacing in five modes of LV, biventricular (BiV) with 20 ms of LV pre-activation (LVRV20), BiV, BiV with 20 ms of RV pre-activation (RVLV20) and RV pacing. Stress was induced by dobutamine infusion up to a maximum of 20 μg/kg/min. Data analyses were the same as chapter one. Dobutamine stress changed the extent of resting-LV MD at all pacing modes. Intrinsic physiologic effects of stress resulted in more accurate MD assessment with lesser variability in subjects who underwent pacing. LVRV20 was the preferred site of stimulation in this model rather than single-site pacing

4D Cardiac MRI Segmentation

Realitzat en col·laboració amb el centre o empresa: Northeastern Universit

Analysis of first pass myocardial perfusion imaging with magnetic resonance

Early diagnosis and localisation of myocardial perfusion defects is an important step in the treatment of coronary artery disease. Thus far, coronary angiography is the conventional standard investigation for patients with known or suspected coronary artery disease and it provides information about the presence and location of coronary stenoses. In recent years, the development of myocardial perfusion CMR has extended the role of MR in the evaluation of ischaemic heart disease beyond the situations where there have already been gross myocardial changes such as acute infarction or scarring. The ability to non-invasively evaluate cardiac perfusion abnormalities before pathologic effects occur, or as follow-up to therapy, is important to the management of patients with coronary artery disease. Whilst limited multi-slice 2D CMR perfusion studies are gaining increased clinical usage for quantifying gross ischaemic burden, research is now directed towards complete 3D coverage of the myocardium for accurate localisation of the extent of possible defects. In 3D myocardial perfusion imaging, a complete volumetric data set has to be acquired for each cardiac cycle in order to study the first pass of the contrast bolus. This normally requires a relatively large acquisition window within each cardiac cycle to ensure a comprehensive coverage of the myocardium and reasonably high resolution of the images. With multi-slice imaging, long axis cardiac motion during this large acquisition window can cause the myocardium imaged in different cross- sections to be mis-registered, i.e., some part of the myocardium may be imaged more than twice whereas other parts may be missed out completely. This type of mis-registration is difficult to correct for by using post-processing techniques. The purpose of this thesis is to investigate techniques for tracking through plane motion during 3D myocardial perfusion imaging, and a novel technique for extracting intrinsic relationships between 3D cardiac deformation due to respiration and multiple ID real-time measurable surface intensity traces is developed. Despite the fact that these surface intensity traces can be strongly coupled with each other but poorly correlated with respiratory induced cardiac deformation, we demonstrate how they can be used to accurately predict cardiac motion through the extraction of latent variables of both the input and output of the model. The proposed method allows cross-modality reconstruction of patient specific models for dense motion field prediction, which after initial modelling can be use in real-time prospective motion tracking or correction. In CMR, new imaging sequences have significantly reduced the acquisition window whilst maintaining the desired spatial resolution. Further improvements in perfusion imaging will require the application of parallel imaging techniques or making full use of the information content of the ¿-space data. With this thesis, we have proposed RR-UNFOLD and RR-RIGR for significantly reducing the amount of data that is required to reconstruct the perfusion image series. The methods use prospective diaphragmatic navigator echoes to ensure UNFOLD and RIGR are carried out on a series of images that are spatially registered. An adaptive real-time re-binning algorithm is developed for the creation of static image sub-series related to different levels of respiratory motion. Issues concerning temporal smoothing of tracer kinetic signals and residual motion artefact are discussed, and we have provided a critical comparison of the relative merit and potential pitfalls of the two techniques. In addition to the technical and theoretical descriptions of the new methods developed, we have also provided in this thesis a detailed literature review of the current state-of-the-art in myocardial perfusion imaging and some of the key technical challenges involved. Issues concerning the basic background of myocardial ischaemia and its functional significance are discussed. Practical solutions to motion tracking during imaging, predictive motion modelling, tracer kinetic modelling, RR-UNFOLD and RR-RIGR are discussed, all with validation using patient and normal subject data to demonstrate both the strength and potential clinical value of the proposed techniques.Open acces

Definition of a four-dimensional continuous planispheric transformation for the tracking and the analysis of left-ventricle motion

International audienceCardiologists assume that analysis of the motion of the heart (especially the left ventricle) can provide useful information about the health of the myocardium. A 4-D polar transformation is defined to describe the left-ventricle (LV) motion and a method is presented to estimate it from sequences of 3-D images. The transformation is defined in 3-D planispheric coordinates (3PC) by a small number of parameters involved in a set of simple linear equations. It is continuous and regular in time and space, and periodicity in time can be imposed. The local motion can be easily decomposed into a few canonical motions (radial motion, rotation around the long-axis, elevation). To recover the motion from original data, the 4-D polar transformation is calculated using an adaptation of the iterative closest-point algorithm. We present the mathematical framework and a demonstration of its feasability on a series of gated SPECT sequences

Foetal echocardiographic segmentation

Congenital heart disease affects just under one percentage of all live births [1]. Those defects that manifest themselves as changes to the cardiac chamber volumes are the motivation for the research presented in this thesis. Blood volume measurements in vivo require delineation of the cardiac chambers and manual tracing of foetal cardiac chambers is very time consuming and operator dependent. This thesis presents a multi region based level set snake deformable model applied in both 2D and 3D which can automatically adapt to some extent towards ultrasound noise such as attenuation, speckle and partial occlusion artefacts. The algorithm presented is named Mumford Shah Sarti Collision Detection (MSSCD). The level set methods presented in this thesis have an optional shape prior term for constraining the segmentation by a template registered to the image in the presence of shadowing and heavy noise. When applied to real data in the absence of the template the MSSCD algorithm is initialised from seed primitives placed at the centre of each cardiac chamber. The voxel statistics inside the chamber is determined before evolution. The MSSCD stops at open boundaries between two chambers as the two approaching level set fronts meet. This has significance when determining volumes for all cardiac compartments since cardiac indices assume that each chamber is treated in isolation. Comparison of the segmentation results from the implemented snakes including a previous level set method in the foetal cardiac literature show that in both 2D and 3D on both real and synthetic data, the MSSCD formulation is better suited to these types of data. All the algorithms tested in this thesis are within 2mm error to manually traced segmentation of the foetal cardiac datasets. This corresponds to less than 10% of the length of a foetal heart. In addition to comparison with manual tracings all the amorphous deformable model segmentations in this thesis are validated using a physical phantom. The volume estimation of the phantom by the MSSCD segmentation is to within 13% of the physically determined volume

Development of novel quantitative medical imaging techniques for MPI and MRI

Tomographic imaging has become indispensable in the clinical routine. In a tomographic scan, images of the inner human body are produced without the need of dissecting the human skin. The common types of medical images are two-dimensional slices and entire three-dimensional volumes. To image dynamic processes such as organ function or perfusion, time series are produced at multiple spatial locations. To date, the most common medical imaging modalities are X-ray imaging, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) or tracer-based imaging such as Positron-Emission Tomography (PET) or Single-Photon Emission Tomography (SPECT). Next to the common modalities, a novel medical imaging modality called Magnetic Particle Imaging (MPI) has been introduced, and its position between the established modalities still needs to be defined. In general, cardiovascular applications impose specific challenges on medical imaging. Imaging speed is required to compensate for respiratory and cardiac motions, and to capture rapid uptake rates of contrast agents in the heart tissue. At the same time, high spatial resolution is demanded to accurately assess cardiac anatomy. In this work, we focus on two main cardiovascular applications: cardiac perfusion imaging and cardiac function imaging. Each imaging modality stands out with particular advantages and drawbacks for cardiovascular imaging. Magnetic Resonance Imaging (MRI), for example, has its main advantage in the use of non-ionizing radiation and its superb soft-tissue contrast and is hence suitable for cardiac function assessment. However, due to non-linearity of the MR signal with the contrast concentration, an application such as cardiac perfusion imaging is challenging and requires complex mathematical and practical treatment to measure the arterial input function. A more adequate tool for application on perfusion imaging would be Magnetic Particle Imaging (MPI) since its signal is linear with the contrast concentration over a wide range of concentration. Yet, a drawback of MPI is that no anatomic information is inside the MPI images since it is a purely tracer-based imaging method such as PET or SPECT. Therefore, image registration is required to fuse anatomic reference scans with MRI or CT with obtained MPI images in order to locate cardiac tissues. Magnetic Particle Imaging (MPI) renders for the application on cardiac perfusion imaging, due to its high spatial and temporal resolution and the linearity of the signal with the contrast concentration. Nevertheless, spatial coverage of MPI is currently limited to small volumes, thus there is a need for extended spatial coverage to assess human tissue structures maintaining high temporal resolution. In this work, methods are explored to extend spatial coverage with the aim to improve image registration of MPI images with anatomic reference scans from MRI or CT. Magnetic Resonance Imaging (MRI) is a suitable tool for cardiac function assessment. Cardiac cine imaging is the standard method to acquire heart motion during the entire cardiac cycle. Though, practical challenges still remain in the clinical application of cardiac cine MRI. The common way to obtain cine images is a stack of slices in short axis and long axis orientation, each acquired during 10-12 separate breath-holds. This is a time-consuming task and can be a tedious procedure especially for elder or illed patients in a clinical scenario. Additionally, due to possible patient movements between the breath-holds, slices at different locations can be miss-aligned leading to decreased accuracy in the assessment of cardiac function. We introduce and implement in this work a novel method for cardiac cine MRI called VF 3D-BRISA (“Very Fast 3D Breath-hold ISotropic Imaging using Spatio-temporal Acceleration”) allowing high image acceleration rates of over 30 and implement it on a real 3T MRI system. The high image acceleration is appreciated to perform non-angulated isotropic 3D cine imaging in a single breath-hold, overcoming the challenges of multi-slice 2D cine imaging. For the objective of this thesis, 2D and 3D experiments are conducted to assess optimal imaging parameters for VF 3D-BRISA. Furthermore, we conduct an in-vivo validation study of VF 3D-BRISA to demonstrate that cardiac function can be assessed with the same accuracy as with a reference method of 2D multi-slice cine imaging.Obtener imágenes mediante equipos de tomografía se ha convertido en una parte indispensable en la rutina clínica. Durante una examinación tomográfica, se producen imágenes del interior del cuerpo humano sin la necesidad disectar la piel humana. La forma más común es a través cortes bidimensionales o volúmenes tridimensionales completos. Para capturar procesos dinámicos tales como la función o la perfusión de un órgano, se adquieren en diferentes momentos y ubicaciones espaciales. Las técnicas de imagen más comunes son típicas de imágenes de rayos X, tomografía computarizada (TAC), resonancia magnética (RM) o de imágenes basadas en trazador: como Tomografía por Emisión de Positrones (PET) o tomografía por emisión de fotón único (SPECT). Paralelo a las modalidades comunes, se ha introducido una técnica nueva llamada Imaging de Partículas Magnéticas (MPI) y su posición entre las modalidades establecidas todavía está por definirse. En general, se imponen retos específicos sobre una aplicación cardiovascular de equipos tomográficos. Se requiere velocidad de adquisición para compensar los movimientos respiratorios y cardíacos, y para capturar bien las tasas de absorción rápida de agentes de contraste en el tejido cardíaco. Al mismo tiempo, se exige una alta resolución espacial para evaluar con más precisión la función cardíaca. En esta tesis, nos centramos en las dos principales aplicaciones cardiovasculares: La imagen de perfusión cardiaca y la imagen de función cardíaca. Cada modalidad de tomografía se destaca con sus ventajas e inconvenientes particulares para aplicaciones cardiovasculares. Imagen por Resonancia Magnética (RM), por ejemplo, tiene su principal ventaja en el uso de las radiaciones no ionizantes y su excelente contraste de los tejidos blandos y, por tanto, es adecuada para la evaluación de la función cardíaco. Sin embargo, debido a la no-linealidad de la señal de RM con la concentración de contraste, obtener imágenes de perfusión cardiaca con la RM es difícil y requiere tratamiento matemático y un manejo complejo para medir la función de entrada arterial (“arterial input function”, AIF). Una herramienta más adecuada para la aplicación en imágenes de perfusión es Imaging de partículas magnéticas (MPI), ya que su señal es lineal con la concentración de contraste en un amplio intervalo de concentración. Sin embargo, un inconveniente de MPI es que no hay información anatómica dentro de las imágenes MPI ya que es un método de formación de imágenes basado a trazadores tal como PET o SPECT, por lo que requiere exploraciones de referencia anatómicos con RM o TAC para la fusión de imágenes con imágenes MPI para localizar la ubicación de tejido cardiaco. Imaging de Partículas Magnéticas (MPI) puede ser adecuada para la aplicación de imágenes de perfusión cardiaca, debido a su alta resolución espacial y temporal y la linealidad de la señal con la concentración de contraste. No obstante, la cobertura espacial de MPI se limita actualmente a pequeños volúmenes, por lo tanto se desea una necesidad de cobertura espacial extendida para evaluar las estructuras de tejido humano. En esta tesis, se trabajan métodos para ampliar la cobertura espacial manteniendo alta resolución temporal. Se estima que una cobertura espacial más amplia mejora el registro de imágenes, de imágenes MPI con imágenes de referencia anatómicas por resonancia magnética o tomografía computarizada. La Resonancia Magnética (RM) es adecuada para la evaluación de la función cardíaca. Es el método estándar para adquirir el latido del ventrículo izquierdo durante todo el ciclo cardíaco a través de las imágenes “cine” cardiaca. Aunque, prevalecen desafíos prácticos aún en la aplicación clínica de MRI cine cardíaco. La forma más común de obtener imágenes de cine cardiacas es a través de un grupo de cortes de orientación en eje corto y eje largo, cada uno adquirido en 10-12 apneas separadas. Esta tarea consume tiempo y puede ser un procedimiento tedioso, especialmente para pacientes ancianos y/o enfermos en un escenario clínico. Además, debido a posibles movimientos del paciente entre la retención de respiración, sectores en diferentes lugares pueden ser mal alineados reduciendo la exactitud en la evaluación de la función cardíaca. En esta tesis, se introduce un nuevo método para resonancia magnética cardiaca llamada VF-3D BRISA ("Very Fast 3D Breath-hold ISotropic Imaging using Spatio-temporal Acceleration") que permite grados altos de aceleración de cine RM cardiaca. Se implementa BRISA en un sistema de RM 3T. Se aprecia esta aceleración alta para adquirir imágenes cine 3D isótropo completo en una sola apnea, superando los retos de la adquisición en múltiples cortes 2D en el estándar cine durante múltiples apneas. Se llevan a cabo experimentos en 2D y 3D para evaluar los parámetros óptimos para la formación de imágenes en 3D VF-BRISA. Además, se lleva a cabo un estudio de validación en vivo de la 3D-VF-BRISA para demostrar que la función cardiaca puede evaluarse con la misma precisión que con el método de referencia utilizando el estándar 2D cine de cortes múltiples.Programa Oficial de Doctorado en Multimedia y ComunicacionesPresidente: Leoncio Garrido Fernández.- Secretario: Juan José Vaquero López.- Vocal: Pedro Luis Sánchez Fernánde

Lung Imaging and Function Assessment using Non-Contrast-Enhanced Magnetic Resonance Imaging

Measurement of pulmonary ventilation and perfusion has significant clinical value for the diagnosis and monitoring of prevalent lung diseases. To this end, non-contrast-enhanced MRI techniques have emerged as a promising alternative to scintigraphical measurements, computed tomography, and contrast-enhanced MRI. Although these techniques allow the acquisition of both structural and functional information in the same scan session, they are prone to robustness issues related to imaging artifacts and post-processing techniques, limiting their clinical utilization. In this work, new acquisition and post-processing techniques were introduced for improving the robustness of non-contrast-enhanced MRI based functional lung imaging. Furthermore, pulmonary functional maps were acquired in 2-year-old congenital diaphragmatic hernia (CDH) patients to demonstrate the feasibility of non-contrast-enhanced MRI methods for functional lung imaging. In the first study, a multi-acquisition framework was developed to improve robustness against field inhomogeneity artifacts. This method was evaluated at 1.5T and 3T field strengths via acquisitions obtained from healthy volunteers. The results demonstrate that the proposed acquisition framework significantly improved ventilation map homogeneity p<0.05. In the second study, a post-processing method based on dynamic mode decomposition (DMD) was developed to accurately identify dominant spatiotemporal patterns in the acquisitions. This method was demonstrated on digital lung phantoms and in vivo acquisitions. The findings indicate that the proposed method led to a significant reduction in dispersion of estimated ventilation and perfusion map amplitudes across different number of measurements when compared with competing methods p<0.05. In the third study, the free-breathing non-contrast-enhanced dynamic acquisitions were obtained from 2-year-old patients after CDH repair, and then processed using the DMD to obtain pulmonary functional maps. Afterwards, functional differences between ipsilateral and contralateral lungs were assessed and compared with results obtained using contrast-enhanced MRI measurements. The results demonstrate that pulmonary ventilation and perfusion maps can be generated from dynamic acquisitions successfully without the need for ionizing radiation or contrast agents. Furthermore, lung perfusion parameters obtained with DMD MRI correlate very strongly with parameters obtained using dynamic contrast-enhanced MRI. In conclusion, the presented work improves the robustness and accuracy of non-contrast-enhanced functional lung imaging using MRI. Overall, the methods introduced in this work may serve as a valuable tool in the clinical adaptation of non-contrast-enhanced imaging methods and may be used for longitudinal assessments of pulmonary functional changes