12A-4 In Vivo 3D Contrast-Enhanced Imaging of the Embryonic Mouse Vasculature

Vascular development depends critically on the proper regulation of many genetic factors, which are being widely studied with genetically-engineered mouse models. Direct in vivo visualization of the developing embryonic vascular system can provide an important tool for analyzing the complex 3- dimensional (3D) networks of vessel growth and patterning in both normal mouse embryos and in mice with mutations exhibiting vascular phenotypes. While micro-MRI has been shown to have the resolution to image the developing embryonic cardiovascular system in mice embryos, it does so in an ex vivo fashion. Ultrasound biomicroscopy (UBM) provides a noninvasive, real-time approach for imaging mouse embryos in utero, enabling dynamic, functional, volumetric and longitudinal studies to be performed. In this study we extend our work of microbubble contrast-enhanced UBM (CE-UBM) to analyze the vascular anatomy in living mouse embryos. By applying image processing algorithms to static and dynamic datasets before and after intracardiac injection of microbubble contrast agent, quantitative and qualitative 2D analysis were performed to study the brain vasculature. 3D respiratory-gated acquisition and digital filtering were used for volumetric segmentation of the major embryonic cerebral vasculature. Our results indicate that with these improvements in hardware and software, the power and sensitivity of CE-UBM has been extended for imaging the developing vascular system from relatively early stages of mouse embryogenesis.