A Rapid and Computationally Inexpensive Method to Virtually Implant Current and Next-Generation Stents into Subject-Specific Computational Fluid Dynamics Models

Computational modeling is often used to quantify hemodynamic alterations induced by stenting, but frequently uses simplified device or vascular representations. Based on a series of Boolean operations, we developed an efficient and robust method for assessing the influence of current and next-generation stents on local hemodynamics and vascular biomechanics quantified by computational fluid dynamics. Stent designs were parameterized to allow easy control over design features including the number, width and circumferential or longitudinal spacing of struts, as well as the implantation diameter and overall length. The approach allowed stents to be automatically regenerated for rapid analysis of the contribution of design features to resulting hemodynamic alterations. The applicability of the method was demonstrated with patient-specific models of a stented coronary artery bifurcation and basilar trunk aneurysm constructed from medical imaging data. In the coronary bifurcation, we analyzed the hemodynamic difference between closed-cell and open-cell stent geometries. We investigated the impact of decreased strut size in stents with a constant porosity for increasing flow stasis within the stented basilar aneurysm model. These examples demonstrate the current method can be used to investigate differences in stent performance in complex vascular beds for a variety of stenting procedures and clinical scenarios

Towards the Systematic Evaluation of Variable Modes of Mechanical Conditioning on the Compositional, Microstructural and Mechanical Properties of Engineered Tissue Vascular Grafts.

Coronary artery bypass surgery (CABG) remains one of the most common cardiac surgical procedures performed worldwide, frequently involving multiple bypasses, and commonly employing the patient’s internal mammary artery, radial artery, or saphenous vein. CABG is often not possible because native vessels were already employed in previous interventions or are diseased themselves. Synthetic vascular grafts are currently integral tools of vascular surgery and have had relative success in large-caliber applications providing substantial benefit to aortic or iliac grafting; however, small diameter (\u3c 6 mm) arterial grafts have not yet translated into clinical effectiveness due to thrombosis and anastomotic intimal hyperplasia. ETVGs present an exciting potential alternative in vascular grafting by offering a blood vessel substitute that could exhibit all the functional characteristics of native vasculature. In addition to relieving supply limitations associated with coronary artery bypass surgery ETVGs are especially ideal for pediatric patients with congenital heart disease who require grafts that grow as they do, eliminating the need for reoccurring invasive surgeries. Though the role of biomechanics in regulating cellular behavior promoting non-thrombogenicity, vasoactivity, and ECM synthesis and maintenance is well established, scientists have yet to find the optimum culture conditions to obtain viable small diameter ETVGs suitable for clinical application. Mechanical conditioning is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to engineered tissues with improved mechanical behaviors. However, determining optimal conditioning protocols for ETVGs is rather empirical and based on extensive trial-and-error iterations. We are unable to predict this cause-and-effect relationship accurately, and thus unable to reliably produce ETVGs with targeted properties. This is only magnified when considering the phase after deployment where the understanding of the in vivo performance of the grafts until fully absorbed is crucial to improve patency

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

Deep learning for cardiac image segmentation: A review

Deep learning has become the most widely used approach for cardiac image segmentation in recent years. In this paper, we provide a review of over 100 cardiac image segmentation papers using deep learning, which covers common imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US) and major anatomical structures of interest (ventricles, atria and vessels). In addition, a summary of publicly available cardiac image datasets and code repositories are included to provide a base for encouraging reproducible research. Finally, we discuss the challenges and limitations with current deep learning-based approaches (scarcity of labels, model generalizability across different domains, interpretability) and suggest potential directions for future research

Development of a Biaxial Stretch Bioreactor and Finite Element Models for Mechanobiological Study of Aortic Valve Leaflets

Aortic heart valve disease is a significant cause of mortality worldwide; and replacement surgery is necessary in 70% of cases. Tissue engineered heart valves (TEHVs) are biocompatible and biodegradable, with ability to grow with the patient. However, to date, TEHVs mostly lack ability to withstand native mechanical forces since they are unable to mimic the heterogeneous and anisotropic structure of extracellular matrix (ECM) in native valves. Cyclic stretch is known to modulate ECM fiber synthesis and alignment. However, little tools are available for studying the interaction between aortic tissues and stretch condition. Finite element method is a powerful tool to simulate the complex structure of aortic valve, however, most current simulations modeled the leaflet as a homogenous material, and none of them took the distinctions between two surface layers into account, which were critical for the proper function of the aortic valve.To study the effects of cyclic stretch on extracellular matrix remodeling, the heterogeneous properties of the aortic leaflet, and the effects of heterogeneity on the function of valve, we have 1) Designed, fabricated and validated a biaxial stretch bioreactor; 2) Analyzed train patterns of native aortic leaflets using digital image correlation method; 3) Designed and validated an anisotropic and heterogeneous finite element (FE) model for leaflets. These studies provided insights into the interaction between aortic valve tissue and the mechanical environment, anisotropy and heterogeneity of aortic leaflets ECM due to the distribution of collagen fibers, and detailed distinct strain patterns in fibrosa vs. ventricularis sides and 3 aortic leaflets. Our novel biaxial stretch bioreactor and refined FE model of aortic leaflet will pave path for other scientists to study mechanobiology, design and condition engineered tissues and simulate engineered aortic valve grafts or pathology of calcium deposition