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

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RAGHUNATHAN-DISSERTATION-2020.pdf (3.23 MB)

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2020-05

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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.

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Brain vasculature, murine embryos, optical coherence tomography, prenatal teratogen exposure, alcohol, nicotine, synthetic cannabinoids

Citation

Portions of this document appear in: Raghunathan, Raksha, Chen Wu, Manmohan Singh, Chih‐Hao Liu, Rajesh C. Miranda, and Kirill V. Larin. "Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography." Journal of biophotonics 11, no. 5 (2018): e201700238. And in: Raghunathan, Raksha, Chih‐Hao Liu, Amur Kouka, Manmohan Singh, Rajesh C. Miranda, and Kirill V. Larin. "Assessing the acute effects of prenatal synthetic cannabinoid exposure on murine fetal brain vasculature using optical coherence tomography." Journal of biophotonics 12, no. 8 (2019): e201900050. And in: Raghunathan, Raksha, Jitao Zhang, Chen Wu, Justin Rippy, Manmohan Singh, Kirill V. Larin, and Giuliano Scarcelli. "Evaluating biomechanical properties of murine embryos using Brillouin microscopy and optical coherence tomography." Journal of biomedical optics 22, no. 8 (2017): 086013. And in: Zhang, Jitao, Raksha Raghunathan, Justin Rippy, Chen Wu, Richard H. Finnell, Kirill V. Larin, and Giuliano Scarcelli. "Tissue biomechanics during cranial neural tube closure measured by Brillouin microscopy and optical coherence tomography." Birth defects research 111, no. 14 (2019): 991-998. And in: Raghunathan, Raksha, Manmohan Singh, Mary E. Dickinson, and Kirill V. Larin. "Optical coherence tomography for embryonic imaging: a review." Journal of biomedical optics 21, no. 5 (2016): 050902.

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https://hdl.handle.net/10657/6691

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