Fetal vascular ultrasound assessment to identify growth restriction and reduce stillbirth

博士项目目标：开发一种方法，使胎儿主动脉弹性特性能够从超声扫描计算；为目前的临床成像系统和最先进的超声成像开发新的超声协议和信号和图像处理技术；研究用这种方法测量的主动脉弹性是否能区分生长受限胎儿和正常胎儿。项目描述：英国每年有超过3000例死产，其中许多与胎儿生长受限（FGR）有关。每200例妊娠中就有1例发生死产，是围产期死亡的主要原因。2016年，《柳叶刀》的“终止可预防的死产系列”表明，英格兰和威尔士的死产率是西欧最高的，在过去20年里几乎没有变化英国最近的一项研究发现，FGR（定义为低于10%的定制出生体重）是死胎率的最大单一因素，约占死胎的43%。减少死产最有希望的方法之一是FGR的早期诊断。研究表明，FGR的高死亡率主要是由于缺乏对该病的认识，而不是由于无法控制该病预防战略主要侧重于改变社会经济参数，如改善获得保健的机会，或改善孕前孕产妇健康，如降低孕产妇肥胖率然而，这些策略很难在当前西方社会的流动、老年和肥胖孕妇人群中实施。因此，需要一种准确筛查FGR的方法来早期诊断FGR。妊娠期FGR的主要筛查工具是胎儿超声（US）扫描，可用于测量胎儿生物测量（尺寸），从而估计胎儿体重，并可用于评估胎儿血流量，从而评估胎儿对缺氧的适应。然而，尽管进行了这些测量，检测FGR的灵敏度仍然小于40%因此，与传统的胎儿生物测定和血流多普勒检查相比，需要一种更灵敏的超声标记来识别在妊娠晚期扫描中未来几周有FGR风险的胎儿。胎儿血管系统的评估正在成为一个新的研究领域，它有可能在更早的阶段提供胎儿心血管适应母体刺激的信息，而不是通过子宫、大脑中动脉和脐动脉的血流多普勒检查来检测。现在可以使用先进的美国技术来评估胎儿主动脉特性，这可能在FGR筛查中有所应用。数据表明，生长受限的胎儿主动脉僵硬度增加，但迄今为止，尚无方法可用于临床实践，以评估妊娠期间的血管弹性。在这项研究中，我们的目标是发展先进的超声和脉搏波分析技术来估计胎儿血管特性。这将包括调查使用原始射频（RF）美国数据，以及最先进的超快美国成像，在整个视野范围内提供更高的时间分辨率。我们将评估这些新技术测量的主动脉弹性是否能区分生长受限胎儿和正常胎儿。如果我们的研究取得成功，这将为提高FGR的检测和降低死产率提供一种新的方法。希望通过我们与佳能医疗系统的合作，该方法可以在美国扫描仪中实施。

Aim of the PhD Project:Develop a methodology which will enable fetal aortic elastic properties to be calculated from an ultrasound scan;Develop new ultrasound protocols and signal and image processing techniques for both current clinical imaging systems and state-of-the-art ultrasound imaging;Investigate whether aortic elasticity measured by this methodology differentiates growth-restricted from normal fetuses.Project description:There are over 3,000 stillbirths per year in the UK, many of which are associated with fetal growth restriction (FGR). Stillbirth affects about 1 in 200 pregnancies and is the leading cause of perinatal death. In 2016, the Lancet's "Ending Preventable Stillbirth Series" indicated that stillbirth rates in England and Wales are the highest in Western Europe and have changed little in the past 20 years.1,2 A recent UK study identified FGR, defined as a customised birthweight below the 10th percentile, as the single largest contributor to stillbirth rates, being responsible for about 43% of stillbirths.3One of the most promising approaches to reduce stillbirths is early diagnosis of FGR. It has been shown that the high mortality rates of FGR are mainly due to lack of recognition of the condition rather than inability to manage it.4 Preventive strategies mostly focus on altering socio-economic parameters, such as improved access to care, or improving maternal wellbeing prior to pregnancy, such as reduced maternal obesity rates.1 However, these strategies are difficult to implement in the mobile, older and more obese pregnant populations of current Western societies. Therefore, a method to accurately screen for FGR to diagnose it early is required.The main screening tool for FGR during pregnancy is fetal ultrasound (US) scanning, which can be used to measure fetal biometry (dimensions) from which fetal weight can be estimated, and fetal blood flow from which fetal adaptation to hypoxia can be assessed. However, despite these measurements, the sensitivity in detecting FGR remains <40%.5 Therefore, a more sensitive ultrasonographic marker is needed - compared to the traditional fetal biometry and blood flow Doppler examination - to identify those fetuses in the third-trimester scan who are at risk of FGR in the next few weeks.Assessment of fetal vasculature is emerging as a novel area of research with potential to provide information about fetal cardiovascular adaptations in response to maternal stimuli at a much earlier stage than can be detected by blood flow Doppler examinations in the uterine, middle cerebral, and umbilical arteries. It is now possible to assess fetal aortic properties using advanced US-based techniques, which may have utility in FGR screening. Data suggest that growth restricted fetuses have increased aortic stiffness,6,7 however to date there is no methodology which can be used in clinical practice to assess vascular elasticity during pregnancy.In this study, we aim to develop advanced US and pulse wave analysis techniques to estimate fetal vascular properties. This will include investigating the use of raw radio-frequency (RF) US data, as well as state-of-the-art ultrafast US imaging8, providing higher temporal resolution across the full field-of-view. We will assess whether aortic elasticity measured by these new techniques differentiates growth-restricted from normal fetuses. If our development is successful, this will provide a novel way to improve detection of FGR and reduce stillbirth rates. It is hoped that the methodology could be implemented in US scanners through our collaboration with Canon Medical Systems.