NOVEL STRATEGIES FOR THE MORPHOLOGICAL AND BIOMECHANICAL ANALYSIS OF THE CARDIAC VALVES BASED ON VOLUMETRIC CLINICAL IMAGES

This work was focused on the morphological and biomechanical analysis of the heart valves exploiting the volumetric data. Novel methods were implemented to perform cardiac valve structure and sub-structure segmentation by defining long axis planes evenly rotated around the long axis of the valve. These methods were exploited to successfully reconstruct the 3D geometry of the mitral, tricuspid and aortic valve structures. Firstly, the reconstructed models were used for the morphological analysis providing a detailed description of the geometry of the valve structures, also computing novel indexes that could improve the description of the valvular apparatus and help their clinical assessment. Additionally, the models obtained for the mitral valve complex were adopted for the development of a novel biomechanical approach to simulate the systolic closure of the valve, relying on highly-efficient mass-spring models thus obtaining a good trade-off between the accuracy and the computational cost of the numerical simulations. In specific: \u2022 First, an innovative and semi-automated method was implemented to generate the 3D model of the aortic valve and of its calcifications, to quantitively describe its 3D morphology and to compute the anatomical aortic valve area (AVA) based on multi-detector computed tomography images. The comparison of the obtained results vs. effective AVA measurements showed a good correlation. Additionally, these methods accounted for asymmetries or anatomical derangements, which would be difficult to correctly capture through either effective AVA or planimetric AVA. \u2022 Second, a tool to quantitively assess the geometry of the tricuspid valve during the cardiac cycle using multidetector CT was developed, in particular focusing on the 3D spatial relationship between the tricuspid annulus and the right coronary artery. The morphological analysis of the annulus and leaflets confirmed data reported in literature. The qualitative and quantitative analysis of the spatial relationship could standardize the analysis protocol and be pivotal in the procedure planning of the percutaneous device implantation that interact with the tricuspid annulus. \u2022 Third, we simulated the systolic closure of three patient specific mitral valve models, derived from CMR datasets, by means of the mass spring model approach. The comparison of the obtained results vs. finite element analyses (considered as the gold-standard) was performed tuning the parameters of the mass spring model, so to obtain the best trade-off between computational expense and accuracy of the results. A configuration mismatch between the two models lower than two times the in-plane resolution of starting imaging data was yielded using a mass spring model set-up that requires, on average, only ten minutes to simulate the valve closure. \u2022 Finally, in the last chapter, we performed a comprehensive analysis which aimed at exploring the morphological and mechanical changes induced by the myxomatous pathologies in the mitral valve tissue. The analysis of mitral valve thickness confirmed the data and patterns reported in literature, while the mechanical test accurately described the behavior of the pathological tissue. A preliminary implementation of this data into finite element simulations suggested that the use of more reliable patient-specific and pathology-specific characterization of the model could improve the realism and the accuracy of the biomechanical simulations

Modelling mitral valvular dynamics–current trend and future directions

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state-of-the-art modelling of the mitral valve, including static and dynamics models, models with fluid-structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed

Computed Tomography-Derived 3D Modeling to Guide Sizing and Planning of Transcatheter Mitral Valve Interventions

A plethora of catheter-based strategies have been developed to treat mitral valve disease. Evolving 3-dimensional (3D) multidetector computed tomography (MDCT) technology can accurately reconstruct the mitral valve by means of 3-dimensional computational modeling (3DCM) to allow virtual implantation of catheter-based devices. 3D printing complements computational modeling and offers implanting physician teams the opportunity to evaluate devices in life-size replicas of patient-specific cardiac anatomy. MDCT-derived 3D computational and 3D-printed modeling provides unprecedented insights to facilitate hands-on procedural planning, device training, and retrospective procedural evaluation. This overview summarizes current concepts and provides insight into the application of MDCT-derived 3DCM and 3D printing for the planning of transcatheter mitral valve replacement and closure of paravalvular leaks. Additionally, future directions in the development of 3DCM will be discussed

Quantitative imaging in cardiovascular CT angiography

In de afgelopen decennia is computertomografie (CT) een prominente niet-invasieve modaliteit om hart- en vaatziekten te evalueren geworden. Dit proefschrift heeft als doel de rol van CT in de therapeutische behandeling van coronaire hartziekte (CAD) en klepaandoeningen te onderzoeken.De relatie tussen kransslagadergeometrie (statisch en dynamisch) en aanwezigheid en omvang van CAD met CT werd onderzocht. De resultaten suggereren dat de statische geometrie van de kransslagader significant gerelateerd is aan de aanwezigheid van plaque en stenose. Er was echter geen verband tussen dynamische verandering van de coronaire arterie-geometrie en de ernst van CAD. Een algoritme om de invloed van intraluminair contrastmiddel op niet-verkalkte atherosclerotische plaque Hounsfield-Unit-waarden te corrigeren werd gepresenteerd en gevalideerd met behulp van fantomen.Diagnose en operatieplanning kunnen cruciale gevolgen hebben voor de klinische uitkomst van chirurgische ingrepen. In dit proefschrift wordt beschreven dat halfautomatische softwareprogramma’s het kwantificeren van het aortaklepgebied betere reproduceerbare resultaten toonden in vergelijking met handmatige metingen, en vergelijkbare resultaten met de huidige gouden standaard, de echocardiografie. Een systematische review over het dynamische gedrag van de aorta-annulus toont aan dat de vorm van de aorta-annulus tijdens de hartcyclus verandert, wat impliceert dat er bij het bepalen van een prothese rekening moet worden gehouden met meerdere fasen. Een andere review beschrijft het gebruik van 3D-printen in de chirurgische planning samen met andere toepassingen voor de behandeling van hartklepaandoeningen.CT is de belangrijkste beeldvormingsmodaliteit in deze onderzoeken, die gericht waren op de therapeutische behandeling van hart- en vaatziekten, van vroege risicobepaling tot diagnose en chirurgische planning.In the recent decades computed tomography (CT) has emerged as a dominant non-invasive modality to evaluate cardiovascular diseases. This thesis aimed to explore the role of CT in the therapeutic management of coronary artery disease (CAD) and valvular diseases.The relationship between both static and dynamic coronary artery geometry and presence and extent of CAD using CT was investigated. The results suggest that the static coronary artery geometry is significantly related to presence of plaque and significant stenosis. However, there were no such relationship between dynamic change of coronary artery geometry and severity of CAD. As part of this thesis an algorithm to correct the influence of lumen contrast enhancement on non-calcified atherosclerotic plaque Hounsfield-Unit values was presented. The algorithm was validated using phantoms. The diagnosis and surgical planning may have crucial impact on clinical outcome. Semi-automatic software for aortic valve area quantification presented in this thesis was proven to be more repeatable and similar to gold standard echocardiography in comparison to manual measurements. The systematic review regarding the dynamic behavior of aortic annulus revealed that aortic annulus geometry changes throughout the cardiac cycle which implies that multiple phases should be taken into account for prosthesis sizing. Another review in this thesis discusses the use of 3D printing in the surgical planning along with other applications for the treatment of valvular diseases.CT is the main imaging modality in these studies which were focused on the therapeutic management of cardiovascular diseases from early risk determination to diagnosis and surgical planning

Investigation and Validation of Imaging Techniques for Mitral Valve Disease Diagnosis and Intervention

Mitral Valve Disease (MVD) describes a variety of pathologies that result in regurgitation of blood during the systolic phase of the cardiac cycle. Decisions in valvular disease management rely heavily on non-invasive imaging. Transesophageal echocardiography (TEE) is widely recognized as the key evaluation technique where backflow of high velocity blood can be visualized under Doppler. In most cases, TEE imaging is adequate for identifying mitral valve pathology, though the modality is often limited from signal dropout, artifacts and a restricted field of view. Quantitative analysis is an integral part of the overall assessment of valve morphology and gives objective evidence for both classification and guiding intervention of regurgitation. In addition, patient-specific models derived from diagnostic TEE images allow clinicians to gain insight into uniquely intricate anatomy prior to surgery. However, the heavy reliance on TEE segmentation for diagnosis and modelling has necessitated an evaluation of the accuracy of the oft-used mitral valve imaging modality. Dynamic cardiac 4D-Computed Tomography (4D-CT) is emerging as a valuable tool for diagnosis, quantification and assessment of cardiac diseases. This modality has the potential to provide a high quality rendering of the mitral valve and subvalvular apparatus, to provide a more complete picture of the underlying morphology. However, application of dynamic CT to mitral valve imaging is especially challenging due to the large and rapid motion of the valve leaflets. It is therefore necessary to investigate the accuracy and level of precision by which dynamic CT captures mitral valve motion throughout the cardiac cycle. To do this, we design and construct a silicone and bovine quasi-static mitral valve phantom which can simulate a range of ECG-gated heart rates and reproduce physiologic valve motion over the cardiac cycle. In this study, we discovered that the dynamic CT accurately captures the underlying valve movement, but with a higher prevalence of image artifacts as leaflet and chordae motion increases due to elevated heart rates. In a subsequent study, we acquire simultaneous CT and TEE images of both a silicone mitral valve phantom and an iodine-stained bovine mitral valve. We propose a pipeline to use CT as the ground truth to study the relationship between TEE intensities and the underlying valve morphology. Preliminary results demonstrate that with an optimized threshold selection based solely on TEE pixel intensities, only 40\% of pixels are correctly classified as part of the valve. In addition, we have shown that emphasizing the centre-line rather than the boundaries of high intensity TEE image regions provides a better representation and segmentation of the valve morphology. This work has the potential to inform and augment the use of TEE for diagnosis and modelling of the mitral valve in the clinical workflow for MVD

Including coronary ostia in patient-specific 3D models of the whole aortic valve apparatus, derived from TEE, for biomechanical simulations

There is an increasing interest in the numerical modeling and simulation of the aortic valve behavior and functioning, on the different stages involved as healthy, stenotic or replacement procedure. As echocardiography is a ubiquitous and economic modality, the geometric model construction based on such images is therefore of major interest. In this paper, a new patient-specific approach for modeling the complete aortic valve apparatus - derived from parameters extracted from 3D transesophageal echocardiographs -that includes for the first time the left ventricle outflow tract and the coronary ostia, both crucial for proper assessment of valve biomechanical behavior, is presented. An innovative method for characterizing coronary pressures from patient-specific clinical data, to be used as boundary conditions for the numerical simulation is also described. Results from experiments were presented to evaluate the novel aspects of the model, that permits to compare the existing models (non-coronary model NCM) and the proposed new coronary model (CM). Variations of displacement and stress on each leaflet prove the need of considering leaflet asymmetry. Computed quantities in the results sections are within the range of physiological data. This permits to conclude that the proposed aortic valve apparatus model of the aortic valve apparatus improves on previous ones by considering this extremely complex structure in greater detail.Xunta de Galicia | Ref. IN606A-2017/02

Advanced Technologies in the Quantification of Mitral Valve

The current study aimed at conducting an educational survey on the mitral valve using advanced technologies eSie Valve® and Q-Lab in echocardiography machines and also those mitral valve geometrical parameter measurements that can be easily calculated with MATLAB software offline in a personal computer as an echocardiographic desk for further information and recommendation before mitral valve repairs or other treatments

DEVELOPMENT AND IMPLEMENTATION OF NOVEL STRATEGIES TO EXPLOIT 3D ULTRASOUND IMAGING IN CARDIOVASCULAR COMPUTATIONAL BIOMECHANICS

Introduction In the past two decades, major advances have been made in cardiovascular diseases assessment and treatment owing to the advent of sophisticated and more accurate imaging techniques, allowing for better understanding the complexity of 3D anatomical cardiovascular structures1. Volumetric acquisition enables the visualization of cardiac districts from virtually any perspective, better appreciating patient-specific anatomical complexity, as well as an accurate quantitative functional evaluation of chamber volumes and mass avoiding geometric assumptions2. Additionally, this scenario also allowed the evolution from generic to patient-specific 3D cardiac models that, based on in vivo imaging, faithfully represent the anatomy and different cardiac features of a given alive subject, being pivotal either in diagnosis and in planning guidance3. Precise morphological and functional knowledge about either the heart valves\u2019 apparatus and the surrounding structures is crucial when dealing with diagnosis as well as preprocedural planning4. To date, computed tomography (CT) and real-time 3D echocardiography (rt3DE) are typically exploited in this scenario since they allow for encoding comprehensive structural and dynamic information even in the fourth dimension (i.e., time)5,6. However, owing to its cost-effectiveness and very low invasiveness, 3D echocardiography has become the method of choice in most situations for performing the evaluation of cardiac function, developing geometrical models which can provide quantitative anatomical assessment7. Complementing this scenario, computational models have been introduced as numerical engineering tools aiming at adding qualitative and quantitative information on the biomechanical behavior in terms of stress-strain response and other multifactorial parameters8. In particular, over the two last decades, their applications have been ranging from elucidating the heart biomechanics underlying different patho-physiological conditions9 to predicting the effects of either surgical or percutaneous procedures, even comparing several implantation techniques and devices10. At the early stage, most of the studies focused on FE modeling in cardiac environment were based on paradigmatic models11\u201315, being mainly exploited to explore and investigate biomechanical alterations following a specific pathological scenario or again to better understand whether a surgical treatment is better or worse than another one. Differently, nowadays the current generation of computational models heavily exploits the detailed anatomical information yielded by medical imaging to provide patient-specific analyses, paving the way toward the development of virtual surgical-planning tools16\u201319. In this direction, cardiac magnetic resonance (CMR) and CT/micro-CT are the mostly accomplished imaging modality, since they can provide well-defined images thanks to their spatial and temporal resolutions20\u201325. Nonetheless, they cannot be applied routinely in clinical practice, as it can be differently done with rt3DE, progressively became the modality of choice26 since it has no harmful effects on the patient and no radiopaque contrast agent is needed. Despite these advantages, 3D volumetric ultrasound imaging shows intrinsic limitations beyond its limited resolution: i) the deficiency of morphological detail owing to either not so easy achievable detection (e.g., tricuspid valve) or not proper acoustic window, ii) the challenge of tailoring computational models to the patient-specific scenario mimicking the morphology as well as the functionality of the investigated cardiac district (e.g., tethering effect exerted by chordal apparatus in mitral valve insufficiency associated to left ventricular dilation), and iii) the needing to systematically analyse devices performances when dealing with real-life cases where ultrasound imaging is the only performable technique but lacking of standardized acquisition protocol. Main findings In the just described scenario, the main aim of this work was focused on the implementation, development and testing of numerical strategies in order to overcome issues when dealing with 3D ultrasound imaging exploitation towards predictive patient-specific modelling approaches focused on both morphological and biomechanical analyses. Specifically, the first specific objective was the development of a novel approach integrating in vitro imaging and finite element (FE) modeling to evaluate tricuspid valve (TV) biomechanics, facing with the lack of information on anatomical features owing to the clinically evident demanding detection of this anatomical district through in vivo imaging. \u2022 An innovative and semi-automated framework was implemented to generate 3D model of TV, to quantitively describe its 3D morphology and to assess its biomechanical behaviour. At this aim, an image-based in vitro experimental approach was integrated with numerical models based on FE strategy. Experimental measurements directly performed on the benchmark (mock circulation loop) were compared with geometrical features computed on the 3D reconstructed model, pinpointing a global good consistency. Furthermore, obtained realistic reconstructions were used as the input of the FE models, even accounting for proper description of TV leaflets\u2019 anisotropic mechanical response. As done experimentally, simulations reproduced both \u201cincompetent\u201d (FTR) and \u201ccompetent-induced\u201d (PMA), proving the efficiency of such a treatment and suggesting translational potential to the clinic. The second specific aim was the implementation of a computational framework able to reproduce a functionally equivalent model of the mitral valve (MV) sub-valvular apparatus through chordae tendineae topology optimization, aiming at chordae rest length arrangement to be able to include their pre-stress state associated to specific ventricular conformation. \u2022 We sought to establish a framework to build geometrically tractable, functionally equivalent models of the MV chordae tendineae, addressing one of the main topics of the computational scientific literature towards the development of faithful patient-specific models from in vivo imaging. Exploiting the mass spring model (MSM) approach, an iterative tool was proposed aiming to the topology optimization of a paradigmatic chordal apparatus of MVs affected by functional regurgitation, in order to be able to equivalently account for tethering effect exerted by the chordae themselves. The results have shown that the algorithm actually lowered the error between the simulated valve and ground truth data, although the intensity of this improvement is strongly valve-dependent.Finally, the last specific aim was the creation of a numerical strategy able to allow for patient-specific geometrical reconstruction both pre- and post- LVAD implantation, in a specific high-risk clinical scenario being rt3DE the only available imaging technique to be used but without any acquisition protocol. \u2022 We proposed a numerical approach which allowed for a systematic and selective analysis of the mechanism associated to intraventricular thrombus formation and thrombogenic complications in a LVAD-treated dilated left ventricle (LV). Ad-hoc geometry reconstruction workflow was implemented to overcome limitations associated to imaging acquisition in this specific scenario, thus being able to generate computational model of the LV assisted with LVAD. In details, results suggested that blood stasis is influenced either by LVAD flow rate and, to a greater extent, by LV residual contractility, being the positioning of the inflow cannula insertion mandatory to be considered when dealing with LVAD thrombogenic potential assessment

Mechanics of the tricuspid valve: from clinical diagnosis/treatment, in vivo and in vitro investigations, to patient-specific biomechanical modeling

Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent undesired backflow of blood from the right ventricle into the right atrium during systole. Various treatment options are currently available for FTR; however, research for the tricuspid heart valve, functional tricuspid regurgitation, and the relevant treatment methodologies are limited due to the pervasive expectation among cardiac surgeons and cardiologists that FTR will naturally regress after repair of left-sided heart valve lesions. Recent studies have focused on (i) understanding the function of the TV and the initiation or progression of FTR using both in-vivo and in-vitro methods, (ii) quantifying the biomechanical properties of the tricuspid valve apparatus as well as its surrounding heart tissue, and (iii) performing computational modeling of the TV to provide new insight into its biomechanical and physiological function. This review paper focuses on these advances and summarizes recent research relevant to the TV within the scope of FTR. Moreover, this review also provides future perspectives and extensions critical to enhancing the current understanding of the functioning and remodeling tricuspid valve in both the healthy and pathophysiological states