Quantifying blood flow dynamics during cardiac development: demystifying computational methods

Abstract

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.

Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease

“…However, if the flow region is relatively small as in the case of embryonic heart, non-Newtonian effects become important. For non-Newtonian modeling of blood, the Carreau–Yasuda model can be used as given in Equation (6) [ 10 , 55 , 56 ]: …”

“…In fact, mechanical forces generated by the blood flow also have an important role in the formation of CHDs [ 7 ]. Hemodynamics govern the cardiac development during the embryonic stage and disturbed hemodynamics is considered to be an important source of CHDs [ 7 , 8 , 9 , 10 , 11 ].…”

Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease

“…Computational models can also capture fetal heart growth and remodeling in response to biomechanical and haemodynamic alterations. These models can be broadly categorized into models of blood flow models ( Courchaine and Rugonyi, 2018 ) and tissue mechanics ( Dewan et al, 2017 ). Fig.…”

Mechanics of development

“…At the largest length scale, there are external 'applied' or 'active' forces (due to, for example, muscle activity, fluid flow or vessel contraction) encompassing most studies of the development of the musculoskeletal system (including [8 -11,12,13] in this issue), and many investigations of cardiovascular development (e.g. [2]). A length scale down, there are forces due to pressure differences or physical constraints (e.g.…”

“…In this Introduction, we wish to highlight the breadth and variety of the research field and so we include recent papers from the broader literature. Research groups across the world are investigating how mechanical forces affect the development of every major organ in the body, including the cardiovascular and lymphatic systems [2][3][4][5][6][7], the musculoskeletal system [3,[8][9][10][11][12][13], the brain [14,15], the eye [16], the neural tube [17,18], the skin [19], the gut [20 -23] and the lung and mammary gland [24][25][26], in addition to the processes that shape the very early embryo, such as gastrulation [27], and mechanotransduction at the cellular or sub-cellular levels during development [28][29][30][31]. A range of animal models are being used, including chick [8][9][10], mouse [8,11] fly [28,[32][33][34] and zebrafish [12 -35] in addition to-or alongside-computational models [2,12,13,36,37].…”