Measuring hemodynamics in the developing heart tube with four-dimensional gated Doppler optical coherence tomography

Abstract

Abstract. Hemodynamics is thought to play a major role in heart development, yet tools to quantitatively assess hemodynamics in the embryo are sorely lacking. The especially challenging analysis of hemodynamics in the early embryo requires new technology. Small changes in blood flow could indicate when anomalies are initiated even before structural changes can be detected. Furthermore, small changes in the early embryo that affect blood flow could lead to profound abnormalities at later stages. We present a demonstration of 4-D Doppler optical coherence tomography (OCT) imaging of structure and flow, and present several new hemodynamic measurements on embryonic avian hearts at early stages prior to the formation of the four chambers. Using 4-D data, pulsed Doppler measurements could accurately be attained in the inflow and outflow of the heart tube. Also, by employing an enface slice from the 4-D Doppler image set, measurements of stroke volume and cardiac output are obtained without the need to determine absolute velocity. Finally, an image plane orthogonal to the blood flow is used to determine shear stress by calculating the velocity gradient normal to the endocardium. Hemodynamic measurements will be crucial to identifying genetic and environmental factors that lead to congenital heart defects. C 2010 Society of Photo-Optical Instrumentation Engineers.

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.…”

Orientation-independent rapid pulsatile flow measurement using dual-angle Doppler OCT

“…The flow rate can be calculated if the cross sectional area of the vessel of interest and the absolute velocity vector everywhere on cross section are known. In cultured avian embryos, which are useful models of heart development that we use regularly [12][13][14][15], vessel cross sectional area is easily measured using optical coherence tomography (OCT) imaging [16]. At the same time, Doppler OCT (DOCT) can provide depth-resolved velocity information with high spatial resolution [17][18][19][20].…”

“…At the same time, Doppler OCT (DOCT) can provide depth-resolved velocity information with high spatial resolution [17][18][19][20]. DOCT has been used to measure blood velocity and the resulting hemodynamic forces on the vessel wall [13,15,21,22], as well as to estimate total flow [23,24]. However, DOCT is only sensitive to motion parallel to the imaging beam, so additional information is needed to obtain the absolute velocity vector in order to calculate absolute flow.…”

“…This calculation only requires measurement of the velocity components normal to the imaging plane. To satisfy this condition a 3-D volume of the vessel is acquired with DOCT and the flow is calculated from an en face section, which is naturally perpendicular to the acquired velocities and illumination beam [13,24,[36][37][38]. The flow calculation does not suffer from the angle error described previously because vessel orientation is not needed.…”

Live four-dimensional optical coherence tomography reveals embryonic cardiac phenotype in mouse mutant

“…While this study only utilized structural OCT imaging, functional OCT methods, such as Doppler OCT, 17 speckle variance OCT, [18][19][20][21][22][23] and OCT-based heart wall dynamic imaging, 24 can potentially be implemented and provide additional information about vascular remodeling and cardiac function.…”