Novel techniques, mainly three-dimensional (3D) reconstructions from image stacks and finite element analysis (FEA), were combined to study the oxygen transport mechanism in the human placenta and its relationship to placental structure. Initial research relates to the development of a platform suitable for realistic computational simulations. The work shows how the 3D architecture of a terminal villus can be accurately reconstructed from confocal laser scanning microscopic (CLSM) images. By combining the resultant 3D structures of terminal villi with finite element analysis, the diffusion of oxygen from the maternal bloodstream towards the fetal blood across the villous membrane is assessed. The results correlate with theoretical studies demonstrating that image-based computational modelling is a robust platform to explore the structure-function relationship in the placenta. Following work deals with the study of blood flow through the fetal capillary network, with particular interest in its role on the oxygen transport capacity of the terminal villi. The computational models are corroborated by a particle image velocimetry (PIV) experiment. The study shows that the variation in capillary diameter is key for effective oxygen uptake by the fetus. The fetus invests minimum energy needed for the blood to travel fast enough in order to provide oxygenated blood, but at the same time slow enough to allow for good oxygenation. This is achieved by the combination of narrow and dilated segments. Additionally, the results demonstrate that there is no vortical flow or whirling. In the subsequent work, the effect of blood properties is investigated. The calculated oxygen flux is 75 times higher than in the previous study (blood flow models), highlighting the importance of haemoglobin molecules in transporting oxygen. Fetal blood affinity is shown to improve fetal oxygen uptake by 11.5%. However, when accounting for haemoglobin concentration the data suggest that the different villous structures have a constant oxygen transport capacity. The methodology developed herein helps to elucidate the structure-function relationship in the human placenta. Additionally, 3D image-based multi-physics computational modelling is demonstrated to be a powerful tool to investigate in detail the mechanics of transport in the human placenta. This technique has the potential to enlighten on the development of pregnancy complications and serve as an in vivo diagnostic tool.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:744601 |
| Date | January 2018 |
| Creators | Plitman Belilty, Romina |
| Contributors | Burton, Graham J. ; Oyen, Michelle L. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.repository.cam.ac.uk/handle/1810/273834 |
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