Placental vascular abnormalities in the mouse alters umbilical artery wave reflections

Current methods to detect placental vascular pathologies that monitor Doppler ultrasound changes in umbilical artery (UA) pulsatility have only moderate diagnostic utility, particularly in late gestation. In fetal mice, we recently demonstrated that reflected pressure waves propagate counter to the direction of flow in the UA, and proposed the measurement of these reflections as a means to detect abnormalities in the placental circulation. In the present study, we used this approach in combination with micro-computed tomography to investigate the relationship between altered placental vascular architecture and changes in UA wave reflection metrics. Fetuses were assessed at embryonic day (E)15.5 and E17.5 in control C57BL6/J mice and dams treated with combination antiretroviral therapy (cART), a known model of fetal growth restriction. Whereas the reflection coefficient was not different between the groups at E15.5, it was 27% higher at E17.5 in cART-treated mice compared to controls. This increase in reflection coefficient corresponded to a 36% increase in the total number of vessel segments, a measure of overall architectural complexity. Interestingly, there was no difference in UA pulsatility index between groups, suggesting that the wave reflections convey information about vascular architecture that is not captured by conventional ultrasound metrics. The wave reflection parameters were found to be associated with the morphology of the feto-placental arterial tree, with the area ratio between the UA and the first branch points correlating with the reflection coefficient. This study highlights the potential for wave reflection to aid the non-invasive clinical assessment of placental vascular pathology.