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

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

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

Geometric description for the anatomy of the mitral valve: A review

The mitral valve is a complex anatomical structure whose physiological functioning relies on the biomechanical properties and structural integrity of its components. Their compromise can lead to mitral valve dysfunction, associated with morbidity and mortality. Therefore, a review on the morphometry of the mitral valve is crucial, more specifically on the importance of valve dimensions and shape for its function. This review initially provides a brief background on the anatomy and physiology of the mitral valve, followed by an analysis of the morphological information available. A characterisation of mathematical descriptions of several parts of the valve is performed and the impact of different dimensions and shape changes in disease is then outlined. Finally, a section regarding future directions and recommendations for the use of morphometric information in clinical analysis of the mitral valve is presented

Fast Surgical Simulation to Improve Mitral Valve Repair

Mitral valve repair, the preferred method of treating mitral regurgitation, is a demanding surgical procedure consisting of the resection and approximation of valve tissue. Operating on an arrested heart, the clinician is forced to predict closed valve shape and the effect of surgical modifications. The valve's complex morphology makes this a difficult task, and as a result, the procedure is underperformed by less experienced surgeons in lieu of the simpler, less effective valve replacement.Engineering and Applied Science

Fusion of interventional ultrasound & X-ray

In einer immer älter werdenden Bevölkerung wird die Behandlung von strukturellen Herzkrankheiten zunehmend wichtiger. Verbesserte medizinische Bildgebung und die Einführung neuer Kathetertechnologien führten dazu, dass immer mehr herkömmliche chirurgische Eingriffe am offenen Herzen durch minimal invasive Methoden abgelöst werden. Diese modernen Interventionen müssen durch verschiedenste Bildgebungsverfahren navigiert werden. Hierzu werden hauptsächlich Röntgenfluoroskopie und transösophageale Echokardiografie (TEE) eingesetzt. Röntgen bietet eine gute Visualisierung der eingeführten Katheter, was essentiell für eine gute Navigation ist. TEE hingegen bietet die Möglichkeit der Weichteilgewebedarstellung und kann damit vor allem zur Darstellung von anatomischen Strukturen, wie z.B. Herzklappen, genutzt werden. Beide Modalitäten erzeugen Bilder in Echtzeit und werden für die erfolgreiche Durchführung minimal invasiver Herzchirurgie zwingend benötigt. Üblicherweise sind beide Systeme eigenständig und nicht miteinander verbunden. Es ist anzunehmen, dass eine Bildfusion beider Welten einen großen Vorteil für die behandelnden Operateure erzeugen kann, vor allem eine verbesserte Kommunikation im Behandlungsteam. Ebenso können sich aus der Anwendung heraus neue chirurgische Worfklows ergeben. Eine direkte Fusion beider Systeme scheint nicht möglich, da die Bilddaten eine zu unterschiedliche Charakteristik aufweisen. Daher kommt in dieser Arbeit eine indirekte Registriermethode zum Einsatz. Die TEE-Sonde ist während der Intervention ständig im Fluoroskopiebild sichtbar. Dadurch wird es möglich, die Sonde im Röntgenbild zu registrieren und daraus die 3D Position abzuleiten. Der Zusammenhang zwischen Ultraschallbild und Ultraschallsonde wird durch eine Kalibrierung bestimmt. In dieser Arbeit wurde die Methode der 2D-3D Registrierung gewählt, um die TEE Sonde auf 2D Röntgenbildern zu erkennen. Es werden verschiedene Beiträge präsentiert, welche einen herkömmlichen 2D-3D Registrieralgorithmus verbessern. Nicht nur im Bereich der Ultraschall-Röntgen-Fusion, sondern auch im Hinblick auf allgemeine Registrierprobleme. Eine eingeführte Methode ist die der planaren Parameter. Diese verbessert die Robustheit und die Registriergeschwindigkeit, vor allem während der Registrierung eines Objekts aus zwei nicht-orthogonalen Richtungen. Ein weiterer Ansatz ist der Austausch der herkömmlichen Erzeugung von sogenannten digital reconstructed radiographs. Diese sind zwar ein integraler Bestandteil einer 2D-3D Registrierung aber gleichzeitig sehr zeitaufwendig zu berechnen. Es führt zu einem erheblichen Geschwindigkeitsgewinn die herkömmliche Methode durch schnelles Rendering von Dreiecksnetzen zu ersetzen. Ebenso wird gezeigt, dass eine Kombination von schnellen lernbasierten Detektionsalgorithmen und 2D-3D Registrierung die Genauigkeit und die Registrierreichweite verbessert. Zum Abschluss werden die ersten Ergebnisse eines klinischen Prototypen präsentiert, welcher die zuvor genannten Methoden verwendet.Today, in an elderly community, the treatment of structural heart disease will become more and more important. Constant improvements of medical imaging technologies and the introduction of new catheter devices caused the trend to replace conventional open heart surgery by minimal invasive interventions. These advanced interventions need to be guided by different medical imaging modalities. The two main imaging systems here are X-ray fluoroscopy and Transesophageal  Echocardiography (TEE). While X-ray provides a good visualization of inserted catheters, which is essential for catheter navigation, TEE can display soft tissues, especially anatomical structures like heart valves. Both modalities provide real-time imaging and are necessary to lead minimal invasive heart surgery to success. Usually, the two systems are detached and not connected. It is conceivable that a fusion of both worlds can create a strong benefit for the physicians. It can lead to a better communication within the clinical team and can probably enable new surgical workflows. Because of the completely different characteristics of the image data, a direct fusion seems to be impossible. Therefore, an indirect registration of Ultrasound and X-ray images is used. The TEE probe is usually visible in the X-ray image during the described minimal-invasive interventions. Thereby, it becomes possible to register the TEE probe in the fluoroscopic images and to establish its 3D position. The relationship of the Ultrasound image to the Ultrasound probe is known by calibration. To register the TEE probe on 2D X-ray images, a 2D-3D registration approach is chosen in this thesis. Several contributions are presented, which are improving the common 2D-3D registration algorithm for the task of Ultrasound and X-ray fusion, but also for general 2D-3D registration problems. One presented approach is the introduction of planar parameters that increase robustness and speed during the registration of an object on two non-orthogonal views. Another approach is to replace the conventional generation of digital reconstructedradiographs, which is an integral part of 2D-3D registration but also a performance bottleneck, with fast triangular mesh rendering. This will result in a significant performance speed-up. It is also shown that a combination of fast learning-based detection algorithms with 2D-3D registration will increase the accuracy and the capture range, instead of employing them solely to the  registration/detection of a TEE probe. Finally, a first clinical prototype is presented which employs the presented approaches and first clinical results are shown

Multi-modality cardiac image computing: a survey

Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, either combining information from different modalities or transferring information across modalities. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, modality selection, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future

Application of Patient-Specific Computational Fluid Dynamics in Coronary and Intra-Cardiac Flow Simulations: Challenges and Opportunities

The emergence of new cardiac diagnostics and therapeutics of the heart has given rise to the challenging field of virtual design and testing of technologies in a patient-specific environment. Given the recent advances in medical imaging, computational power and mathematical algorithms, patient-specific cardiac models can be produced from cardiac images faster, and more efficiently than ever before. The emergence of patient-specific computational fluid dynamics (CFD) has paved the way for the new field of computer-aided diagnostics. This article provides a review of CFD methods, challenges and opportunities in coronary and intra-cardiac flow simulations. It includes a review of market products and clinical trials. Key components of patient-specific CFD are covered briefly which include image segmentation, geometry reconstruction, mesh generation, fluid-structure interaction, and solver techniques

Shear wave echocardiography

In this thesis we demonstrate that the assessment of the diastolic function of the left ventricle withclassical echocardiography remain