Biomechanics of the Chick Embryonic Heart Outflow Tract at HH18 Using 4D Optical Coherence Tomography Imaging and Computational Modeling

Abstract

During developmental stages, biomechanical stimuli on cardiac cells modulate genetic programs, and deviations from normal stimuli can lead to cardiac defects. Therefore, it is important to characterize normal cardiac biomechanical stimuli during early developmental stages. Using the chicken embryo model of cardiac development, we focused on characterizing biomechanical stimuli on the Hamburger–Hamilton (HH) 18 chick cardiac outflow tract (OFT), the distal portion of the heart from which a large portion of defects observed in humans originate. To characterize biomechanical stimuli in the OFT, we used a combination of in vivo optical coherence tomography (OCT) imaging, physiological measurements and computational fluid dynamics (CFD) modeling. We found that, at HH18, the proximal portion of the OFT wall undergoes larger circumferential strains than its distal portion, while the distal portion of the OFT wall undergoes larger wall stresses. Maximal wall shear stresses were generally found on the surface of endocardial cushions, which are protrusions of extracellular matrix onto the OFT lumen that later during development give rise to cardiac septa and valves. The non-uniform spatial and temporal distributions of stresses and strains in the OFT walls provide biomechanical cues to cardiac cells that likely aid in the extensive differential growth and remodeling patterns observed during normal development.

Blood flow through the embryonic heart outflow tract during cardiac looping in HH13–HH18 chicken embryos

“…The time of flow was measured for all embryos from clearly distinguishable periods of blood flow in the velocity versus time trace from each developmental stage between HH13 and HH18 (n ¼ 10). Time of flow, the percentage of time in the cardiac cycle when blood was flowing (main surge), was approximately half of the cardiac cycle for all embryos, consistent with our previous observations at HH18 [30]. The time of flow stayed near constant over the analysed developmental stages and increased slightly between HH13 and HH18 from 41.9 + 4.3% to 53.3 + 8.4%, respectively.…”

“…Overall, WSR remained relatively constant from HH13 to HH14, substantially increased from HH14 to HH15, and then steadily decreased with advanced stage reaching initial HH13 levels by HH18 (figure 4d). WSR was computed at the time of peak V, assuming a circular lumen with equation (2.4), which is a good approximation when the OFT walls are fully expanded [30,34]. The fluctuation in WSR from HH13 to HH18 was accompanied by a large increase in lumen maximum diameter between HH15 and HH18, where the initial increase in WSR preceded the increase in lumen diameter.…”

“…SV calculations likely overestimate actual values, since the estimation assumes that the OFT is a circular cylinder over the entire cardiac cycle. OCT images from a cross-sectional plane of the OFT show that while the myocardium concentrically contracts and expands over the cardiac cycle, the lumen is shaped like an ellipse (although almost circular) at maximum expansion and a slit at maximum contraction [30,34]. Even though this method simplifies the dynamic and complex geometry of the OFT, it does account for the changes in lumen diameter and velocity over the cardiac cycle to serve as a comparison of SV across developmental stages.…”

“…Others have defined the diastolic filling characteristics of the embryonic heart, including ventricular pressure, dorsal aortic velocity and atrioventricular blood velocity [27][28][29]. More recently, four-dimensional OCT has been used in conjunction with computational modelling to analyse the biomechanics through the OFT at HH18 [30,31]. This study focused on haemodynamics in the OFT.…”

Dynamic imaging and quantitative analysis of cranial neural tube closure in the mouse embryo using optical coherence tomography

“…Embryology is a major research area where OCT shows great promise as a high-resolution unlabeled imaging tool [31][32][33]. With the primary focus on the cardiovascular development and abnormalities, OCT has been reported able to reveal detailed structures of the embryonic heart comparable to histology [34][35][36], to capture four-dimensional dynamic cardiac activities [37][38][39], to quantify biomechanics of the heart tube [40][41][42], to assess cardiac hemodynamics [43][44][45], to characterize novel mutant heart phenotypes [46][47][48], and to investigate cardiac responses to physical and chemical manipulations [49][50][51][52]. Focusing on the mouse model, our group has combined OCT with live embryo culture to establish a number of structural and functional imaging methods [39,45,48,[53][54][55], suggesting an important role of OCT for in vivo analysis of the mammalian embryo.…”