Functional imaging of human placental structure, blood flow, and oxygenation.

 描述(申请人提供)：胎盘在决定妊娠结局方面的重要性是不可否认的，然而，当胎盘完成其功能并超过其寿命时，接触这一独特器官的机会在很大程度上仅限于产后。充分了解正常妊娠和异常妊娠的胎盘发育情况，对于识别有并发症风险的患者，确定有风险妊娠的生物标志物，为有风险的妊娠开发有针对性的治疗方法，以及在临床试验中适当地对患者进行分层是至关重要的。我们对胎盘功能和发育的了解的一个根本限制是我们无法定量评估基本的功能输出，如血流和氧合。我们的建议试图通过利用基于磁共振成像(MRI)的方法来克服这些限制。具体地说，我们的多学科小组设计了一种MRI数据采集和分析方案，该方案结合了灵长类胎盘独特的血管结构组织，我们认为这对于将非侵入性成像数据转换为与胎盘功能和损害机制相关的定量解剖和生理参数至关重要。这种新的方法利用内源性对比来量化母体胎盘的血流灌注，已经在临床前的动物模型中得到验证，现在准备过渡到人类应用。因此，这项建议的目标是优化人类妊娠的内源性造影剂MR采集方案，采用我们之前开发的3D分析工具来分析人体非造影剂灌注图的建模依赖于造影剂的数据，并确定基础数据，这些数据将建立正常和高危人类妊娠期间孕妇胎盘灌注量的纵向正常变化，重点关注吸烟作为胎盘功能的环境扰动。我们建议对两个地点的300名孕妇进行纵向前瞻性队列研究：俄亥俄州立大学和犹他大学。所有研究参与者将在怀孕期间(12-16周、26-28周和32-34周)接受三次胎盘MRI扫描，并在分娩时收集胎盘组织。受试者将根据三个队列的选择标准进行招募：1)非吸烟者，2)吸烟者和3)不良妊娠结局的高危人群。我们的科学方法将使我们能够产生数据，证明怀孕期间孕妇胎盘血流的正常变化。在血管受损的高危女性(即吸烟者和有胎盘功能不全病史的女性)中应用我们的内源性对比磁共振成像方案，将使我们能够测试这项新技术预测不良临床结果的敏感性和特异性。这些工具的成功开发将极大地促进胎盘功能的非侵入性成像，因为它创造了一种方法，在保留人类胎盘特有的空间和生理特征的同时，定量地确定胎盘的灌注量。

 DESCRIPTION (provided by applicant): The importance of the placenta in determining pregnancy outcome is undeniable, yet access to this unique organ is largely limited to post-delivery when it has completed its function and exceeded its lifespan. An adequate understanding of placental development in both normal and abnormal pregnancies is critical to identify patients at risk for complications, to determine biomarkers for at risk pregnancies, to develop targeted therapeutics for pregnancies at risk, and to appropriately stratify patients in clinical trials. A fundamental limitation in our understanding of placental function and development is our inability to quantitatively assess basic functional outputs such as blood flow and oxygenation. Our proposal seeks to overcome these limitations by utilizing a magnetic resonance imaging (MRI)-based approach. Specifically, our multidisciplinary group has designed a MRI data acquisition and analysis protocol that incorporates the unique vascular structural organization of the primate placenta, which we believe is critical for converting non-invasive imaging data into quantitative anatomical and physiological parameters of relevance to placenta function and mechanisms of impairment. This new approach utilizes endogenous contrast to quantify maternal perfusion of the placenta, has been validated in a pre-clinical animal model and is now ready to be transitioned to human application. The objective of this proposal is therefore to optimize the endogenous contrast MR acquisition protocols for human pregnancy, adapt the 3D analysis tools we previously developed for analyzing contrast-dependent data for modeling of non-contrast perfusion maps in humans, and ascertain fundamental data that will establish the normal variance of placental perfusion in pregnant women longitudinally across gestation in normal and at-risk human pregnancies, focusing on smoking as an environmental perturbation of placental function. We are proposing a longitudinal prospective cohort study of 300 pregnant women across two sites: OHSU and the University of Utah. All study participants will undergo three placental MRI scans across gestation (12-16, 26-28 and 32-34 weeks gestation) and placental tissue will be collected at the time of delivery. Subjects will be recruited based on selection criteria in three cohorts: 1) non-smokers, 2) smokers and 3) high risk for adverse pregnancy outcome. Our scientific approach will allow us to generate data that will demonstrate the normal variance of placental perfusion in pregnant women across gestation. Application of our endogenous contrast MRI protocol in women at high risk for vascular compromise (i.e., smokers and those with a prior history of placental insufficiency) will allow us to test the sensitivity and specificity of this new techniqu for predicting adverse clinical outcomes. Successful development of these tools will significantly advance non-invasive imaging of placental function by creating a method that quantitatively determines placental perfusion while preserving the spatial and physiologic characteristics unique to the human placenta.