4D shear stress maps of the developing heart using Doppler optical coherence tomography

Abstract

Accurate imaging and measurement of hemodynamic forces is vital for investigating how physical forces acting on the embryonic heart are transduced and influence developmental pathways. Of particular importance is blood flow-induced shear stress, which influences gene expression by endothelial cells and potentially leads to congenital heart defects through abnormal heart looping, septation, and valvulogenesis. However no imaging tool has been available to measure shear stress on the endocardium volumetrically and dynamically. Using 4D structural and Doppler OCT imaging, we are able to accurately measure the blood flow in the heart tube in vivo and to map endocardial shear stress throughout the heart cycle under physiological conditions for the first time. These measurements of the shear stress patterns will enable precise titration of experimental perturbations and accurate correlation of shear with the expression of molecules critical to heart development.

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.…”

Congenital heart malformations induced by hemodynamic altering surgical interventions

“…Chick embryos, in particular, are often used as a biological model of cardiac development because of ease of accessibility in the egg, including easy access for surgical manipulations to alter blood flow, and developmental similarities with human embryos (including the formation of a four-chamber heart). The availability of advanced in vivo imaging techniques (such as optical coherence tomography and ultrasound biomicroscopy) has allowed access to measuring and monitoring embryonic hemodynamic conditions over developmental stages, and to assess acute changes in hemodynamics after interventions that alter blood flow conditions (McQuinn et al, 2007; Rugonyi et al, 2008; Hu et al, 2009; Liu et al, 2012; Peterson et al, 2012). The chicken embryo has therefore been extensively used to study the effects of hemodynamic alterations on cardiac development.…”

Functional optical coherence tomography: principles and progress

“…three-dimensional (3D) OCT images taken over time, to measure the shear stress in the developing hearts of quail embryos. 15 …”