Using optical coherence tomography to rapidly phenotype and quantify congenital heart defects associated with prenatal alcohol exposure

Abstract

Background The most commonly used method to analyze congenital heart defects involves serial sectioning and histology. However, this is often a time-consuming process where the quantification of cardiac defects can be difficult due to problems with accurate section registration. Here we demonstrate the advantages of using optical coherence tomography, a comparatively new and rising technology, to phenotype avian embryo hearts in a model of Fetal Alcohol Syndrome where a binge-like quantity of alcohol/ethanol was introduced at gastrulation. Results The rapid, consistent imaging protocols allowed for the immediate identification of cardiac anomalies, including ventricular septal defects and misaligned/missing vessels. Interventricular septum thicknesses and vessel diameters for three of the five outflow arteries were also significantly reduced. Outflow and atrio-ventricular valves were segmented using image processing software and had significantly reduced volumes compared to controls. This is the first study to our knowledge that has 3-D reconstructed the late-stage cardiac valves in precise detail in order to examine their morphology and dimensions. Conclusion We believe therefore that OCT, with its ability to rapidly image and quantify tiny embryonic structures in high resolution, will serve as an excellent and cost-effective preliminary screening tool for developmental biologists working with a variety of experimental/disease models.

Optical Coherence Tomography for Brain Imaging and Developmental Biology

“…tethers connecting the endocardium to the myocardium) [132], as well as assessment of fast dynamics of a beating heart in vivo . Next, we focus our discussion on applications of OCT on heart development in various animal models, including Xenopus [11, 133–135], zebrafish [40, 136], avian [43, 137–144], mouse [44, 145–154]and Drosophila [45, 155–163]. …”

“…Cardiac defects in avian embryos caused by ethanol exposure at the gastrulation stage were studied with OCT. These defects included muscular ventricular septal defects, missing or misaligned great vessels, double outlet right ventricle, to hypoplastic or abnormally rotated ventricles [143, 144]. …”

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.…”

Rotational imaging optical coherence tomography for full-body mouse embryonic imaging

“…[42][43][44] The noninvasive nature, relatively rapid imaging speed, and minimal computational complexity means that RI-OCT can provide high-throughput imaging for largescale phenotyping projects that heavily rely on evaluating phenotypic outcomes.…”