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

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

Artificial intelligence and automation in valvular heart diseases

Artificial intelligence (AI) is gradually changing every aspect of social life, and healthcare is no exception. The clinical procedures that were supposed to, and could previously only be handled by human experts can now be carried out by machines in a more accurate and efficient way. The coming era of big data and the advent of supercomputers provides great opportunities to the development of AI technology for the enhancement of diagnosis and clinical decision-making. This review provides an introduction to AI and highlights its applications in the clinical flow of diagnosing and treating valvular heart diseases (VHDs). More specifically, this review first introduces some key concepts and subareas in AI. Secondly, it discusses the application of AI in heart sound auscultation and medical image analysis for assistance in diagnosing VHDs. Thirdly, it introduces using AI algorithms to identify risk factors and predict mortality of cardiac surgery. This review also describes the state-of-the-art autonomous surgical robots and their roles in cardiac surgery and intervention

Development of a Surgical Assistance System for Guiding Transcatheter Aortic Valve Implantation

Development of image-guided interventional systems is growing up rapidly in the recent years. These new systems become an essential part of the modern minimally invasive surgical procedures, especially for the cardiac surgery. Transcatheter aortic valve implantation (TAVI) is a recently developed surgical technique to treat severe aortic valve stenosis in elderly and high-risk patients. The placement of stented aortic valve prosthesis is crucial and typically performed under live 2D fluoroscopy guidance. To assist the placement of the prosthesis during the surgical procedure, a new fluoroscopy-based TAVI assistance system has been developed. The developed assistance system integrates a 3D geometrical aortic mesh model and anatomical valve landmarks with live 2D fluoroscopic images. The 3D aortic mesh model and landmarks are reconstructed from interventional angiographic and fluoroscopic C-arm CT system, and a target area of valve implantation is automatically estimated using these aortic mesh models. Based on template-based tracking approach, the overlay of visualized 3D aortic mesh model, landmarks and target area of implantation onto fluoroscopic images is updated by approximating the aortic root motion from a pigtail catheter motion without contrast agent. A rigid intensity-based registration method is also used to track continuously the aortic root motion in the presence of contrast agent. Moreover, the aortic valve prosthesis is tracked in fluoroscopic images to guide the surgeon to perform the appropriate placement of prosthesis into the estimated target area of implantation. An interactive graphical user interface for the surgeon is developed to initialize the system algorithms, control the visualization view of the guidance results, and correct manually overlay errors if needed. Retrospective experiments were carried out on several patient datasets from the clinical routine of the TAVI in a hybrid operating room. The maximum displacement errors were small for both the dynamic overlay of aortic mesh models and tracking the prosthesis, and within the clinically accepted ranges. High success rates of the developed assistance system were obtained for all tested patient datasets. The results show that the developed surgical assistance system provides a helpful tool for the surgeon by automatically defining the desired placement position of the prosthesis during the surgical procedure of the TAVI.Die Entwicklung bildgeführter interventioneller Systeme wächst rasant in den letzten Jahren. Diese neuen Systeme werden zunehmend ein wesentlicher Bestandteil der technischen Ausstattung bei modernen minimal-invasiven chirurgischen Eingriffen. Diese Entwicklung gilt besonders für die Herzchirurgie. Transkatheter Aortenklappen-Implantation (TAKI) ist eine neue entwickelte Operationstechnik zur Behandlung der schweren Aortenklappen-Stenose bei alten und Hochrisiko-Patienten. Die Platzierung der Aortenklappenprothese ist entscheidend und wird in der Regel unter live-2D-fluoroskopischen Bildgebung durchgeführt. Zur Unterstützung der Platzierung der Prothese während des chirurgischen Eingriffs wurde in dieser Arbeit ein neues Fluoroskopie-basiertes TAKI Assistenzsystem entwickelt. Das entwickelte Assistenzsystem überlagert eine 3D-Geometrie des Aorten-Netzmodells und anatomischen Landmarken auf live-2D-fluoroskopische Bilder. Das 3D-Aorten-Netzmodell und die Landmarken werden auf Basis der interventionellen Angiographie und Fluoroskopie mittels eines C-Arm-CT-Systems rekonstruiert. Unter Verwendung dieser Aorten-Netzmodelle wird das Zielgebiet der Klappen-Implantation automatisch geschätzt. Mit Hilfe eines auf Template Matching basierenden Tracking-Ansatzes wird die Überlagerung des visualisierten 3D-Aorten-Netzmodells, der berechneten Landmarken und der Zielbereich der Implantation auf fluoroskopischen Bildern korrekt überlagert. Eine kompensation der Aortenwurzelbewegung erfolgt durch Bewegungsverfolgung eines Pigtail-Katheters in Bildsequenzen ohne Kontrastmittel. Eine starrere Intensitätsbasierte Registrierungsmethode wurde verwendet, um kontinuierlich die Aortenwurzelbewegung in Bildsequenzen mit Kontrastmittelgabe zu detektieren. Die Aortenklappenprothese wird in die fluoroskopischen Bilder eingeblendet und dient dem Chirurg als Leitfaden für die richtige Platzierung der realen Prothese. Eine interaktive Benutzerschnittstelle für den Chirurg wurde zur Initialisierung der Systemsalgorithmen, zur Steuerung der Visualisierung und für manuelle Korrektur eventueller Überlagerungsfehler entwickelt. Retrospektive Experimente wurden an mehreren Patienten-Datensätze aus der klinischen Routine der TAKI in einem Hybrid-OP durchgeführt. Hohe Erfolgsraten des entwickelten Assistenzsystems wurden für alle getesteten Patienten-Datensätze erzielt. Die Ergebnisse zeigen, dass das entwickelte chirurgische Assistenzsystem ein hilfreiches Werkzeug für den Chirurg bei der Platzierung Position der Prothese während des chirurgischen Eingriffs der TAKI bietet

Fully Automatic 3D-TEE Segmentation for the Planning of Transcatheter Aortic Valve Implantation

A novel fully automatic framework for aortic valve (AV) trunk segmentation in three-dimensional (3-D) transesophageal echocardiography (TEE) datasets is proposed. The methodology combines a previously presented semiautomatic segmentation strategy by using shape-based B-spline Explicit Active Surfaces with two novel algorithms to automate the quantification of relevant AV measures. The first combines a fast rotation-invariant 3-D generalized Hough transform with a vessel-like dark tube detector to initialize the segmentation. After segmenting the AV wall, the second algorithm focuses on aligning this surface with the reference ones in order to estimate the short-axis (SAx) planes (at the left ventricular outflow tract, annulus, sinuses of Valsalva, and sinotubular junction) in which to perform the measurements. The framework has been tested in 20 3-D-TEE datasets with both stenotic and nonstenotic AVs. The initialization algorithm presented a median error of around 3 mm for the AV axis endpoints, with an overall feasibility of 90%. In its turn, the SAx detection algorithm showed to be highly reproducible, with indistinguishable results compared with the variability found between the experts' defined planes. Automatically extracted measures at the four levels showed a good agreement with the experts' ones, with limits of agreement similar to the interobserver variability. Moreover, a validation set of 20 additional stenotic AV datasets corroborated the method's applicability and accuracy. The proposed approach mitigates the variability associated with the manual quantification while significantly reducing the required analysis time (12 s versus 5 to 10 min), which shows its appeal for automatic dimensioning of the AV morphology in 3-D-TEE for the planning of transcatheter AV implantation.This work was supported by the project "ON.2 SR&TD Integrated Program (Norte-07-0124-FEDER-000017)" cofunded by the Programa Operacional Regional do Norte (ON.2- O Novo Norte), Quadro de Referencia Estrategico Nacional, through Fundo Europeu de Desenvolvimento Regional. The work of S. Queiros and P. Morais was supported by the FCT-Fundacao para a Ciencia e a Tecnologia and the European Social Found through the Programa Operacional Capital Humano in the scope of the Ph.D. Grants SFRH/BD/93443/2013 and SFRH/BD/95438/2013, respectively. J. L. Vilaca and J. D'hooge are joint last authors. Asterisk indicates corresponding author.info:eu-repo/semantics/publishedVersio

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

Mitral valve regurgitation assessed by intraventricular CMR 4D-flow: a systematic review on the technological aspects and potential clinical applications.

Cardiac magnetic resonance (CMR) four-dimensional (4D) flow is a novel method for flow quantification potentially helpful in management of mitral valve regurgitation (MVR). In this systematic review, we aimed to depict the clinical role of intraventricular 4D-flow in MVR. The reproducibility, technical aspects, and comparison against conventional techniques were evaluated. Published studies on SCOPUS, MEDLINE, and EMBASE were included using search terms on 4D-flow CMR in MVR. Out of 420 screened articles, 18 studies fulfilled our inclusion criteria. All studies (n = 18, 100%) assessed MVR using 4D-flow intraventricular annular inflow (4D-flowAIM) method, which calculates the regurgitation by subtracting the aortic forward flow from the mitral forward flow. Thereof, 4D-flow jet quantification (4D-flowjet) was assessed in 5 (28%), standard 2D phase-contrast (2D-PC) flow imaging in 8 (44%) and the volumetric method (the deviation of left ventricle stroke volume and right ventricular stroke volume) in 2 (11%) studies. Inter-method correlations among the 4 MVR quantification methods were heterogeneous across studies, ranging from moderate to excellent correlations. Two studies compared 4D-flowAIM to echocardiography with moderate correlation. In 12 (63%) studies the reproducibility of 4D-flow techniques in quantifying MVR was studied. Thereof, 9 (75%) studies investigated the reproducibility of the 4D-flowAIM method and the majority (n = 7, 78%) reported good to excellent intra- and inter-reader reproducibility. Intraventricular 4D-flowAIM provides high reproducibility with heterogeneous correlations to conventional quantification methods. Due to the absence of a gold standard and unknown accuracies, future longitudinal outcome studies are needed to assess the clinical value of 4D-flow in the clinical setting of MVR