UCLA

Cardiovascular and correlated metabolomic diseases remain the leading cause of death in the United States and around the world. Three-dimensional (3-D) and real-time imaging techniques for investigating cardiovascular physiology and pathology mechanisms remain a significant challenge. In this thesis, I first introduce advanced light-sheet microscopy that enables multi-dimensional and multi-scale imaging via illuminating specimens with a thin sheet of the laser. This imaging strategy allows rapid data acquisition with a high spatiotemporal resolution, minimal photo-bleaching, and photo-toxicity. Its multiscale capability also empowers us to image and investigate the cardiovascular physiology and pathology at the scales from zebrafish embryos to adult mouse hearts and even human organs. Secondly, the custom-build light-sheet system was established and optimized to investigate the retinas in the embryonic mouse model. By combining light-sheet with tissue-clearing and computational quantification, we revealed the 3-D retinal microvascular network including primary (inner) and secondary (outer) plexuses as well as the vertical sprouts bridging the two plexuses. Whereas, in an oxygen-induced retinopathy (OIR) mouse model, we demonstrated preferential obliteration of the secondary plexus and bridging vessels with a relatively unscathed primary plexus. Using clustering coefficients and Euler numbers, we computed the local versus global vascular connectivity. While local connectivity was preserved, the global vascular connectivity in OIR retinas was significantly reduced. Overall, the application of 3-D LSFM images coupled with computational quantification provides vascular insights into OIR, with translational significance for developing therapeutic interventions to prevent visual impairment. Thirdly, we developed electrical impedance tomography (EIT) as a non-invasive and portable detection method for fatty infiltrate in the liver. Since non-alcoholic fatty liver disease (NAFLD) is still endemic in developed countries and is one of the most common causes of cardiometabolic diseases, there is an unmet clinical need for non-invasive and cost-effective monitoring of fatty liver disease. The current gold diagnosis standard is liver biopsy which is prone to bleeding and has the risk of complications and sampling errors. Using acquired voltage data and the reconstruction algorithm for the EIT imaging, we computed the absolute conductivity distribution of the abdomen in 2-D. We performed correlation analyses to compare the individual EIT conductivity vs. MRI PDFF. Our results demonstrated that EIT conductivity (S/m) is inversely correlated with the MRI proton-density fat fraction percentage (PDFF%) in the liver. This inverse correlation holds promises for developing non-invasive and portable liver EIT for early detection of fatty liver content in overweight individuals.