Assessing Teratogen-Induced Changes in Murine Fetal Brain Vasculature Using In Utero Optical Coherence Tomography

Abstract

This dissertation reports the use of in utero optical coherence tomography to evaluate changes in vasculature in a developing murine fetal brain caused due to prenatal exposure to teratogens. Embryogenesis is a highly complex process that is extremely vulnerable to external factors. Proper visualization of embryonic development is crucial to understand the basic physiological processes and identify defects if any. This dissertation is divided into two major sections: 1) assessing teratogen induced changes in the murine fetal brain vasculature during the second trimester equivalent period (chapters 2-4) and 2) combining optical coherence tomography with Brillouin microscopy to image and evaluate changes in biomechanical properties during neural tube closure in order to study first trimester exposure to teratogens (appendix A3). The first section is further divided into the following sub-sections: 1) assessing alcohol induced changes in murine fetal brain vasculature, 2) assessing nicotine induced changes in murine fetal brain vasculature, and 3) assessing synthetic cannabinoid (SCB) induced changes in murine fetal brain vasculature. The advancement of algorithms to image and detect minute changes in vasculature are also detailed. The contributions of this work are significant to understand the effects of teratogens on development, as blood flow plays a major role in embryogenesis. Understanding the acute changes in vasculature caused within minutes of maternal exposure to a teratogen can open several new avenues to explore as blood flow drives organ development. Results from this dissertation have been published in 7 first author peer-reviewed publications.