High-frequency ultrasound for in vivo, 3D imaging and analysis of mouse embryo brain development

High-throughput, fine-resolution, in utero imaging methods are urgently required to analyze the dynamics of brain growth and patterning in mouse embryos. To address this need, a 5-ring, 38-MHz, annular-array ultrasound imaging system was developed to obtain three-dimensional (3D) data from individual, in utero embryos. Data were collected with the annular array, synthetically focused and then imported into 3D visualization software for segmentation and quantitative analysis. The head and ventricles of the embryo were reconstructed in 3D, and volume and surface areas were computed for each embryo data set. The data were then analyzed to establish quantitative parameters of normal brain development, such as surface area and volume, as well as other morphometric parameters, such as the pontine flexure angle. Detailed studies of volumetric changes associated with mouse brain development were performed by acquiring 3D data from 148 embryos spanning the early-to-mid gestational stages of E10.5-14.5.