Novel Models for Haemodynamics and Transport in Complex Media: Towards Precision Healthcare for Placental Disorders

早产和死产影响到所有分娩的10%，包括在发达国家，如英国。在这些并发症中，先兆子痫，或通过胎盘在母亲和胎儿之间的血液供应受损，仅在英国，NHS和公共部门服务每年就花费超过12亿英镑用于新生儿和婴儿护理。人类胎盘是发育中的胎儿的重要生命支持系统。母亲血液中氧气和营养物质的供应必须在复杂的胎儿血管网络中得到很好的协调。我们在了解胎盘结构和功能的相互作用方面进展有限有两个原因：一方面，人类胎盘具有非常复杂的结构;另一方面，人类胎盘的结构和生理学是独特的，因此动物研究的用途有限。缺乏了解的一个直接后果是非常有限的选择临床管理妊娠疾病，如先兆子痫和胎儿生长受限。此外，胎盘功能不全不仅会导致死胎或早产，而且还与心脏病发作、中风、对这些挑战的认识导致了最近世界范围内研究兴趣的激增，并建立了一个新的研究领域，41 M美国人类胎盘项目和欧盟胎盘学网络，用于怀孕期间化学品安全性的实验和理论测试。此外，最近在用于极早产儿生命支持的“人工胎盘”设计方面的突破，为通过正常人类胎盘的系统性“逆向工程”进行设计优化提供了新的机会。因此，英国需要大量的胎盘技术专业知识，以匹配美国和欧盟的能力，并保持在这一重要领域的国际合作的积极参与者。根据我们迄今为止的研究，我们假设，胎盘中的血流和营养运输在先兆子痫和胎儿生长受限中发生改变。在这个项目中，我们提出了一种跨学科的创新方法，利用我们的理论和实验专业知识为产科和新生儿重症监护提供精准医学。我们将开发和验证一个框架，用于基于图像的建模和模拟患者特定胎盘中的血流和营养运输。由于现有的数据集描述了健康和患病胎盘的结构，我们将能够探索胎盘中的哪些解剖学变化与营养转运受损相关。这将为开发用于治疗先兆子痫和胎儿生长受限的干预措施和人工解决方案建立良好的理论基础。长期转化影响包括（i）基于模型的患者特异性治疗，使用药物避免高危妊娠中的胎盘功能障碍，以及（ii）设计优化“人工胎盘”以支持极早产儿。

Pre-term and stillbirths affect up to 10% of all deliveries, including in developed countries, such as the UK. Among these complications, pre-eclampsia, or the compromised supply of blood between mother and fetus via the placenta, costs over £1.2 billion each year in neonatal and infant care to the NHS and public sector services in the UK alone.The human placenta is a vital life-support system for the developing fetus. The supply of oxygen and nutrients by the mother's blood has to be well orchestrated within a complex fetal blood vessel network. There are two reasons for our limited progress in the understanding of the interaction of the structure and the function of the placenta: on the one hand, the human placenta has an extraordinarily complex structure; on the other hand, the structure and physiology of the human placenta are unique and therefore animal studies are of limited use. A direct consequence of the lack of understanding are very limited options for clinical management of pregnancy diseases such as pre-eclampsia and fetal growth restriction. Furthermore, placental insufficiency does not only result in stillbirth or premature delivery, but it has also been associated with a higher risk of heart attack, stroke, diabetes or neurological disorders later in adult life.Recognition of these challenges has resulted in a recent surge of research interest world-wide and in establishing the $41M US Human Placenta Project and the EU Placentology Network for experimental and theoretical testing of chemicals' safety in pregnancy. Moreover, a recent breakthrough in 'artificial placenta' design for life-support of extremely premature infants offers new opportunities for design optimisation by systematic 'reverse engineering' of the normal human placenta. Thus, the UK needs a critical mass of expertise in placental technologies to match the US and EU capacities and to remain an active player in international collaborations in this important area.Based on our research to date, we hypothesise that blood flow and nutrient transport in the placenta are altered in pre-eclampsia and fetal growth restriction. In this project, we propose an interdisciplinary and innovative approach harnessing our theoretical and experimental expertise to deliver precision medicine for obstetrics and neonatal critical care. We will develop and validate a framework for image-based modelling and simulation of blood flow and nutrient transport in patient-specific placentas. Thanks to existing datasets describing the structure of both healthy and diseased placentas, we will be able to explore which anatomical changes in the placenta are associated with compromised nutrient transport. This will establish a sound theoretical basis for the development of interventions and artificial solutions for the treatment of pre-eclampsia and fetal growth restriction. The long-term translational impacts include (i) model-based patient-specific treatment with drugs avoiding placental dysfunction in high-risk pregnancies and (ii) design optimisation of an 'artificial placenta' for the support of extremely premature babies.