Imaging Innovations for Placental Assessment in Response to Environmental Pollution

摘要/项目总结 许多流行病学研究表明，接触机动车造成的交通空气污染、 工业和其他环境毒素的孕妇与措施，包括先兆子痫的不良出生结果 (PE)早产（PTB）和宫内生长受限（IUGR）。先兆子痫，早产和IUGR，统称 被称为缺血性胎盘疾病，与婴儿发病率和许多成人疾病密切相关， 从冠心病到癌症尽管人们普遍认为，导致 缺血性胎盘病和胎盘功能不全的并发症具有相似的生物学起源， 胎盘植入缺陷，迄今为止还没有前瞻性检查胎盘结构的预测研究 和/或功能。该提案的目的是开发和评估一套尖端的多参数磁 磁共振成像（mp-MRI）技术，并将这些新的胎盘成像模式转化为评估 环境污染暴露对胎盘功能不全的预测作用。我们的核心假设是， 暴露于高比率的环境污染，独立于社会经济地位（SES）， 由于妊娠早期不良胎盘结构/功能发育导致的胎盘功能不全，通过mp检测- MRI技术进步为了验证这一假设，我们在加州大学洛杉矶分校的跨学科研究团队将首先开发非 对比自由呼吸胎盘mp-MRI，包括多延迟伪连续动脉自旋标记（pCASL） 灌注和高分辨率多对比结构MRI，这将提供胎盘灌注的准确测量 和组织微结构（AIM 1）。新的mp-MRI技术将与子宫动脉多普勒进行比较 超声通过怀孕，并最终验证了金标准的组织病理学和血管的 产后胎盘（AIM 2）。最后，我们将对招募的受试者进行深入分析， 环境污染，并将其暴露率与广泛收集的妊娠结果相关联， 建立预测模型（AIM 3）。这些研究将确定环境污染对胎盘的影响， 结构和功能，以及相关的妊娠结局，产科和新生儿实践包括监测 根据孕妇及其子女的居住地点采取的战术。此外，拟议的研究将 建立早期识别胎盘功能不全的可能性，从而制定未来的预防和 在遇到有害后果之前进行靶向逆转的介入治疗。

ABSTRACT/PROJECT SUMMARY Many epidemiological studies have associated exposure to traffic-derived air pollution from motor vehicles, air toxics from industry and other environmental toxins by pregnant women with measures of poor birth outcomes including preeclampsia (PE), preterm birth (PTB) and intra-uterine growth restriction (IUGR). Preeclampsia, preterm birth and IUGR, collectively known as ischemic placental disease, are strongly correlated with infant morbidity and a host of adult diseases ranging from coronary artery disease to cancer. Although it is widely believed that the pathophysiological mechanisms leading to complications of ischemic placental disease and placental insufficiency have similar biological origins, starting as early as defective placental implantation, to date there are no predictive studies that prospectively examine placental structure and/or function. The objective of this proposal is to develop and evaluate a suit of cutting-edge multi-parametric magnetic resonance imaging (mp-MRI) technologies and translate these novel placental imaging modalities to assessing the impact of environmental pollution exposure on prediction of placental insufficiency. Our central hypothesis is that chronic exposure to high rates of environmental pollution, independent of socio-economic status (SES), increases the risk of placental insufficiency due to early gestational development of adverse placental structure/function as detected by mp- MRI technological advances. To test this hypothesis, our interdisciplinary research team at UCLA will first develop non- contrast free-breathing placental mp-MRI, consisting of multi-delay pseudo-continuous arterial spin labeling (pCASL) perfusion and high-resolution multi-contrast structural MRI, which will provide accurate measures of placental perfusion and tissue microstructure (AIM 1). The novel mp-MRI techniques will be compared to the uterine artery Doppler ultrasound through pregnancy, and validated ultimately by the gold standard histological pathology and vascularity of the post-parturient placenta (AIM 2). Lastly, we will perform in-depth analyses of recruited subjects for exposure to environmental pollution and correlate their rates of exposure to extensively collected pregnancy outcomes, towards building a predictive model (AIM 3). These studies will establish the impact of environmental pollution on placental structure and function, and related pregnancy outcomes, with obstetric and neonatal practices embracing surveillance tactics based on the residential location of pregnant women and their offspring. In addition, the proposed research will establish the potential for early recognition of placental insufficiency, thereby staging future strategies of preventive and interventional therapies targeting reversal before encountering detrimental consequences.