Understanding abnormal uterine artery Doppler waveforms: a novel computational model to explore potential causes within the utero-placental vasculature

Introduction: Uterine artery (UtA) Doppler indices are one of the most commonly employed screening tests for pre-eclampsia worldwide. Abnormal indices appear to result from increased uterine vascular resistance, but anatomical complexity and lack of appropriate animal models mean that little is known about the relative contribution of each of the components of the uterine vasculature to the overall UtA Doppler waveform. Previous computational models suggested that trophoblast-mediated spiral artery remodeling has a dominant effect on the UtA Doppler waveform. However, these models did not incorporate the myometrial arterio-venous anastomoses, which have significant potential to affect utero-placental haemodynamics. Methods: We present a more anatomically complete computational model, explicitly incorporating a structural description of each component of the uterine vasculature, and crucially including myometrial arterio-venous anastomoses as parallel pathways for blood-flow away from the placental bed. Wave transmission theory was applied to the network to predict UtA waveforms. Results: Our model shows that high UtA resistance indices, combined with notching, reflect an abnormal remodeling of the entire uterine vasculature. Incomplete spiral artery remodeling alone is unlikely to cause abnormal UtA Doppler waveforms as increased resistance in these arteries can be ‘buffered’ by upstream anastomoses. Critically, our results indicate that the radial arteries, may have a more important effect on utero-placental flow dynamics, and the UtA Doppler waveform than previously thought. Conclusions: This model suggests that to appropriately interpret UtA Doppler waveforms they must be considered to be reflecting changes in the entire system, rather than just the spiral arteries.