PROJECT SUMMARY/ABSTRACT
Congenital heart defects are present in 1.8% of newborns and account for one third of congenital defects. Despite
all the research that has been done, 80% of cases have no identifiable causes. Biomechanical factors are known
to regulate cardiac development, but the lack of methods to analyze flow in live embryos limits progress in
biomechanical studies. Mouse models have revealed much about cardiovascular development, but
biomechanical studies are extremely limited as imaging motion in embryonic hearts requires high speed, spatial
resolution, and imaging depth. Our lab’s recent advancements in optical coherence tomography (OCT) uniquely
meet these requirements for live embryo imaging through the heart, but quantitative flow tracking remains
inadequate despite the critical importance of blood flow. This project aims to develop a novel optical coherence
tomography (OCT) based method for volumetric, dynamic, and quantitative analysis of blood flow based on the
hypothesis that temporal spatial analysis of pixel fluctuation in OCT images over multiple cardiac cycles can
reveal quantitative measures of blood flow. In this cross disciplinary project, I will combine live mouse embryo
dissection and culture, optimize a custom operation protocol for our lab’s house-built OCT system, and develop
quantitative approaches for OCT image processing. This method will be applied to build the first 4D (volume +
time) map of early mouse embryonic blood flow and will set a platform for functional cardiovascular phenotyping.
Structural OCT imaging will be performed on cultured mouse embryos on embryonic day 8.5 (E8.5) volumetrically
and heartbeats aligned based on previously established methods. The proposed flow speed analysis will be
based on the duration each pixel detects a particle, particle size statistics, optical microangiography, and the
periodicity of the cardiac cycle. Doppler OCT in regions of defined orientation will be used as calibration and
validation. The proposed quantitative OCT angiography approach for blood flow analysis in the early mouse
embryonic cardiovascular system will be applied to build the first 4D quantitative cardiac flow pattern in early
embryos. Implementation of this approach in existing mouse models of congenital heart defects will provide
insight into the interplay between genetic and biomechanical factors in cardiac development and disease,
contributing to better diagnostics, prevention, and early treatment of human congenital heart disease.
Through this fellowship, I will master unique cross-disciplinary skills ranging from mouse embryo dissection,
custom-built imaging systems, quantitative approaches for OCT image processing, and cardiodynamic
development analysis. I will train with experts in development, optics, computation, and cardiovascular biology
to advance my scientific career at the frontier of cardiovascular biomechanics.