Multimodal Imaging Combining Optical Coherence Tomography and Brillouin Microscopy to Study Neural Tube Biomechanics

This dissertation reports the development of a novel, non-invasive, all-optical, and co-aligned multimodal imaging technique which combines optical coherence tomography (OCT) and Brillouin microscopy to determine the structural and biomechanical properties of embryonic neurulation in a murine model. Mechanical forces play a major role during neurulation, and any disturbance can lead to severe birth defects such as spina bifida which result in lifelong disabilities after birth. Thus, it is very important to study the interplay between forces and tissue stiffness during neural tube development. OCT and Brillouin microscopy are high-resolution optical imaging modalities, where OCT provides structural information and Brillouin microscopy is capable of mapping tissue biomechanics. This multimodal approach enables mechanical characterization of the neural tube tissue in mouse models of neural tube defects. The first chapter of this dissertation introduces the importance of biomechanics for neural tube closure and available imaging techniques. The second chapter describes the development of a Brillouin microscopy system to characterize tissue mechanical properties and its validation using optical coherence elastography and the gold standard of uniaxial mechanical testing. The third chapter demonstrates the performance of the home-built Brillouin microscopy system by characterizing fresh and fixed mouse retinas. The fourth chapter demonstrates the development of the first-ever multimodal Brillouin-OCT system and illustrates its use in imaging the dynamic structure and changes in biomechanical properties of neural tube formation and closure in ex vivo murine embryos at different developmental stages. In the fifth and sixth chapters, the biomechanical properties of Mthfd1l and Fuz knockout mouse embryos are successfully assessed using the multimodal Brillouin-OCT system. Finally, this thesis concludes with ideas on improving the technical aspects of the system and future applications.