This study found that although increased ILT is associated with lower MWS and PWS, it is also associated with aneurysm rupture at smaller diameters and lower stress. Therefore, the protective biomechanical advantage that ILT provides by lowering wall stress seems to be outweighed by weakening of the AAA wall, particularly in patients with small rAAAs. This study suggests that high ILT burden may be a surrogate marker of decreased aortic wall strength and a characteristic of high-risk small aneurysms.

The role of hemodynamics in cardiovascular development is not well understood. Indeed, it would be remarkable if it were, given the dauntingly complex array of intricately synchronized genetic, molecular, mechanical, and environmental factors at play. However, with congenital heart defects affecting around 1 in 100 human births, and numerous studies pointing to hemodynamics as a factor in cardiovascular morphogenesis, this is not an area in which we can afford to remain in the dark. This review seeks to present the case for the importance of research into the biomechanics of the developing cardiovascular system. This is accomplished by i) illustrating the basics of some of the highly complex processes involved in heart development, and discussing the known influence of hemodynamics on those processes; ii) demonstrating how altered hemodynamic environments have the potential to bring about morphological anomalies, citing studies in multiple animal models with a variety of perturbation methods; iii) providing examples of widely used technological innovations which allow for accurate measurement of hemodynamic parameters in embryos; iv) detailing the results of studies in avian embryos which point to exciting correlations between various hemodynamic manipulations in early development and phenotypic defect incidence in mature hearts; and finally, v) stressing the relevance of uncovering specific biomechanical pathways involved in cardiovascular formation and remodeling under adverse conditions, to the potential treatment of human patients. The time is ripe to unravel the contributions of hemodynamics to cardiac development, and to recognize their frequently neglected role in the occurrence of heart malformation phenotypes.

One contribution of 14 to a Theo Murphy meeting issue 'Mechanics of development'.Blood flow conditions (haemodynamics) are crucial for proper cardiovascular development. Indeed, blood flow induces biomechanical adaptations and mechanotransduction signalling that influence cardiovascular growth and development during embryonic stages and beyond. Altered blood flow conditions are a hallmark of congenital heart disease, and disrupted blood flow at early embryonic stages is known to lead to congenital heart malformations. In spite of this, many of the mechanisms by which blood flow mechanics affect cardiovascular development remain unknown. This is due in part to the challenges involved in quantifying blood flow dynamics and the forces exerted by blood flow on developing cardiovascular tissues. Recent technologies, however, have allowed precise measurement of blood flow parameters and cardiovascular geometry even at early embryonic stages. Combined with computational fluid dynamics techniques, it is possible to quantify haemodynamic parameters and their changes over development, which is a crucial step in the quest for understanding the role of mechanical cues on heart and vascular formation. This study summarizes some fundamental aspects of modelling blood flow dynamics, with a focus on three-dimensional modelling techniques, and discusses relevant studies that are revealing the details of blood flow and their influence on cardiovascular development.

Cardiogenesis is interdependent with blood flow within the embryonic system. Recently, a number of studies have begun to elucidate the effects of hemodynamic forces acting upon and within cells as the cardiovascular system begins to develop. Changes in flow are picked up by mechanosensors in endocardial cells exposed to wall shear stress (the tangential force exerted by blood flow) and by myocardial and mesenchymal cells exposed to cyclic strain (deformation). Mechanosensors stimulate a variety of mechanotransduction pathways which elicit functional cellular responses in order to coordinate the structural development of the heart and cardiovascular system. The looping stages of heart development are critical to normal cardiac morphogenesis and have previously been shown to be extremely sensitive to experimental perturbations in flow, with transient exposure to altered flow dynamics causing severe late stage cardiac defects in animal models. This paper seeks to expand on past research and to begin establishing a detailed baseline for normal hemodynamic conditions in the chick outflow tract during these critical looping stages. Specifically, we will use 4-D (3-D over time) optical coherence tomography to create in vivo geometries for computational fluid dynamics simulations of the cardiac cycle, enabling us to study in great detail 4-D velocity patterns and heterogeneous wall shear stress distributions on the outflow tract endocardium. This information will be useful in determining the normal variation of hemodynamic patterns as well as in mapping hemodynamics to developmental processes such as morphological changes and signaling events during and after the looping stages examined here.

Cardiac pumping depends on the morphological structure of the heart, but also on its sub-cellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three dimensional (3D) heart structure, to assess malformations; and its ultrastructure, to assess organelle disruptions. We present here a multiscale, correlative imaging procedure that achieves high-resolution images of the whole heart, using 3D micro-computed tomography (micro-CT); and its ultrastructure, using 3D scanning electron microscopy (SEM). In a small animal model (chicken embryo), we achieved uniform fixation and staining of the whole heart, without losing ultrastructural preservation on the same sample, enabling correlative multiscale imaging. Our approach enables multiscale studies in models of congenital heart disease and beyond.