Cardiovascular Assessment of Fetal Mice by In Utero Echocardiography

Abstract

To establish a developmental profile of fetal mouse cardiovascular parameters, we analyzed a large body of ultrasound measurements obtained by in utero echocardiography of C57BL/6J fetal mice from embryonic day 12.5 to 19.5 (term). Measurements were obtained using 2D, spectral Doppler and M-mode imaging with standard clinical cardiac ultrasound imaging planes. As these studies were conducted as part of a large scale mouse mutagenesis screen, stringent filtering criteria were used to eliminate potentially abnormal fetuses. Our analysis showed heart rate increased from 190 to 245 bpm as the mouse fetus grew from 8 mm at embryonic day 12.5 to 18.7 mm at term. This was accompanied by increases in peak outflow velocity, E-wave, E/A ratio and ventricular dimensions. In contrast, the A-wave, myocardial performance index and isovolemic contraction time decreased gradually. Systolic function remained remarkably stable at 80% ejection fraction. Analysis of intra and interobserver variabilities showed these parameters were reproducible, with most comparing favorably to clinical ultrasound measurements in human fetuses. A comprehensive database was generated comprising 23 echocardiographic parameters delineating fetal mouse cardiovascular function from embryonic day 12.5 to term. This database can serve as a standard for evaluating cardiovascular pathophysiology in genetically altered and mutant mouse models.

In utero, high-frame-rate mouse embryo cardiovascular retrospective imaging using 40 MHz annular array and Doppler-derived synchronization signals

“…Figure 3a shows the mean cardiac cycle waveform obtained after 2 minutes of acquisition of the Doppler signals from an E13.5, in vivo, in utero mouse embryo. The mean cycle duration was 300±10 ms, i.e., a heart rate of 200 beats/min, which was consistent with previous measurements on similarly staged embryos [11], [12]. The blood flow from the descending aorta was detected in 100% of the 10 embryos imaged.…”

Imaging modalities to assess structural birth defects in mutant mouse models

“…Ultrasound imaging is now commonly used for in vivo mouse phenotyping, including the noninvasive interrogation of fetuses in utero (Leatherbury et al, 2003;Yu et al, 2008). This imaging modality is well developed for clinical applications.…”

“…mice (Phoon et al, 2000;Momoi et al, 2008;Yu et al, 2008;Pallares et al, 2009;Corrigan et al, 2010). Thus with the ultrasound biomicroscope, it is possible to quantitatively assess blood flow velocity and obtain other measurements of cardiovascular function using M-mode echocardiogram, color-flow Doppler imaging and pulsed-wave Doppler for blood flow velocity mapping, tissue Doppler imaging, and speckle tracking measurements (Leatherbury et al, 2003;Shen et al, 2005;Momoi et al, 2008;Yu et al, 2008).…”

“…Thus with the ultrasound biomicroscope, it is possible to quantitatively assess blood flow velocity and obtain other measurements of cardiovascular function using M-mode echocardiogram, color-flow Doppler imaging and pulsed-wave Doppler for blood flow velocity mapping, tissue Doppler imaging, and speckle tracking measurements (Leatherbury et al, 2003;Shen et al, 2005;Momoi et al, 2008;Yu et al, 2008). With speckle tracking, it is possible to quantitatively assess regional myocardial wall motion and obtain measurements of ventricular mechanics (Hu and Clark, 1989;Keller et al, 1996;Tobita and Keller, 1999;Tobita and Keller, 2000;Ishiwata et al, 2003;Leatherbury et al, 2008;Watanabe et al, 2009;Frank et al, 2010).…”

Three-Dimensional (3D) Visualisation of the Cardiovascular System of Mouse Embryos and Fetus

“…For mouse embryos, 2D (B-mode) ultrasound can beand is -used for analysing heart morphology and blood flow in the late fetal and perinatal period [42,43]. For human fetus ultrasound data can be even used for creating 3D models of various fetal structures [44][45][46][47][48][49].…”