Investigating rat feto-placental vascular structure and Haemodynamics

Introduction: Optimal feto-placental vascular development is critical for fetal development; regulating nutrient, oxygen and waste transfer [1]. The aim of this study is to dissect the relationship between feto-placental vascular structure and function by modelling the haemodynamics in rat models of control and intrauterine growth restricted (IUGR) feto-placental arterial networks. Methods: Time-mated Wistar rats were administered with vehicle or 0.5 μg/ml dexamethasone acetate (dex) via drinking water from E13 – E21. Arterial feto-placental vasculature was cast, and computational modelling followed our previous work [2]. Briefly, we scanned the solidified casts with micro-CT (~7.1µm resolution) and automatically segmented vessels into 3D on Amira 6.2.0. Skeletons of the networks were converted into rooted trees from which graph statistics were used to derive number of segments, volume, vessel length and diameter on Matlab R2016a. Geometries were converted into computational meshes (~12 M elements) of polyhedral elements, with prism elements at the near-wall boundary layer. We used high-frequency Doppler ultrasound measurements of umbilical arterial velocity as input, split outlet flow based on Murray’s law and implemented the Fahræus-Lindqvist effect. We then ran simulations on a supercomputer (Magnus, Cray XC40) and compared the structure and haemodynamics of one control and dex geometry. Centreline velocity was monitored and wall shear stress (WSS) was calculated and reported as a function of radius. Results: Fetal and placental weights were decreased due to dex-exposure by 14 and 34% respectively (p<0.001). There were striking differences in vessel geometry between the control and dex models with reduction of segment number, total volume and length by 145, 95 and 105% respectively (Matlab analysis and Fig 1A and B). Compared to the dex geometries, velocity was 62% (p<0.001) higher and WSS was 65% (p<0.05) higher in the smaller vessels (<60 µm) of the control model. However, the average WSS in vessels below 400 µm was only 9% higher in the control (4.64 Pa) compared to the dex (4.25 Pa) geometry. Discussion: Our preliminary findings show that compared to control, WSS was lower in the dex model. WSS is a stimulus for angiogenesis and thus, may underly the less elaborate vasculature due to dex-exposure. Moreover, the difference in velocities may influence oxygen transfer mechanisms between fetal and maternal blood. This work forms the basis of a larger effort to use computational modelling and both in vivo and in vitro experiments to elucidate the relationship between placental vascular structure and haemodynamics on placental and fetal outcomes. References: 1. Wyrwoll et al, PNAS, 113(22): 6265-70, 2016. 2. Bappoo et al, Biomech Model Mechanobiol, 16(4):1361-1372, 2017. Acknowledgements: We would like to acknowledge funding support from the National Health and Medical Research Council (grants APP1063986 and APP1083572). This work was supported by resources provided by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia.