Measuring blood flow in the mouse embryo

Abstract

Extensive genetic information and the recent introduction of transgenic techniques for genetic manipulation have made the mouse the accepted model for normal cardiac development and congenital heart disease. An impediment to progress in this area has been the lack of noninvasive technologies to assess embryonic cardiovascular structure and function. The authors have developed a high frequency (40-50 MHz) ultrasound imaging and Doppler system enabling in vivo analysis of early embryonic cardiovascular development in the mouse. Simultaneous real-time image and Doppler data can be obtained noninvasively allowing, for the first time, measurements to be made of inflow and outflow characteristics of the mouse embryo heart and blood flow in the umbilical circulation. High resolution (measured lateral resolution=60-100 /spl mu/m) images are used to position the sample volume of the Doppler transducers. The 40 MHz CW Doppler system utilizes a pair of air backed LiNbO/sub 3/ transducers mounted on SMB connectors, and has been calibrated with a string phantom from 10 to 300 mm/s, velocities relevant to embryonic cardiovascular blood waveforms. Biphasic inflow waveforms were measured in normal 10 day mouse embryos (approximately equivalent to 4 weeks human) with peak blood velocities close to 200 mm/s. Outflow velocities in the same embryos were close to 70 mm/s while umbilical artery velocities were approximately 20 mm/s. Future studies will compare normal velocity data to measurements of mutant mice with specific defects in heart and placenta.