Biomechanical force exerted by early blood flow regulates heart development and alterations can result in congenital heart defects. To investigate dynamics during early cardiac development in mouse models of human disease, optical coherence tomography (OCT) based functional analysis methods are actively being developed. Here, by integrating and expanding recent OCT cardiodynamic techniques, we demonstrate a quantitative OCT angiography method capable of dynamic, volumetric flow analysis in embryonic vasculature and within the beating heart. The presented method will allow biomechanical studies of the role that early blood flow plays in regulating mammalian heart development.
Congenital heart defects represent one in three congenital defects and are present in an estimated 1.8% of newborns worldwide. Mouse models provide an irreplaceable resource for studying mammalian development and early cardiogenesis. Early dynamics of circulation during heart development are understood to influence heart formation, but quantitative assessment of spatially and temporally resolved blood flow in the highly dynamic embryonic hearts remains challenging. Optical coherence tomography (OCT) uniquely provides the high speed, spatial resolution, and imaging depth necessary to study biomechanics early in heart development. Building off advancements in Doppler OCT and quantitative OCT angiography, we present dynamic, volumetric (4D) speed analysis of blood flow in the embryonic cardiovascular system. Our new flow tracking method is based on time-at-pixel measurements, blood cell size statistics, and the periodicity of the cardiac cycle. We characterize the effects of detection thresholds to account for variation in signal intensity, such as due to lower light penetration over tissue depth throughout the heart or when comparing between embryos. We incorporate segmentation methods using speckle variance between cycles to expand the analysis from manually defined blood vessels to dynamic regions of blood flow. With these advancements, we quantify blood flow speed within the embryonic mouse heart as it beats. The presented method will allow biomechanical studies of early blood flow in regulating mammalian heart development.
Alterations in cardiac development lead to embryonic lethality or congenital heart defects, which affect about 1% of all newborns worldwide. The heart is critical for blood circulation to transport oxygen, nutrients, and waste, but proper blood flow is also key to cardiac development. Early heart contractility and blood flow are suggested by multiple studies to be biomechanical factors that regulate cardiovascular development. Therefore, the ability to reconstruct the dynamic patterns of blood flow in the developing embryos is important to understanding the biomechanical regulation of heart development and improved management of congenital heart defects. Toward this goal, optical coherence tomography (OCT) imaging of mouse embryonic cardiodynamics and novel OCT-based functional analysis methods are actively being developed. Here, we present the development of quantitative OCT angiography toward direction-independent, spatially and temporally resolved blood flow analysis in embryonic vascular structures, which could potentially be expanded to the heart. In contrast to adult blood, individual blood cells can be visualized within the embryonic cardiovascular system. Our approach takes advantage of this feature as well as the periodicity of the cardiac cycle. We demonstrate a capability for spatially resolved flow dynamics in embryonic vasculature in relation to the heartbeat phase. Potentially, the presented method can be expanded to 4D (3D + time) quantitative OCT angiography in the beating heart to enable biomechanical studies.
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