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

 描述（由申请人提供）：胎盘在决定妊娠结局方面的重要性是不可否认的，但对这一独特器官的访问在很大程度上限于分娩后，当它完成其功能并超过其寿命时。充分了解正常和异常妊娠中的胎盘发育对于识别有并发症风险的患者，确定高危妊娠的生物标志物，开发高危妊娠的靶向治疗方法以及在临床试验中对患者进行适当分层至关重要。我们对胎盘功能和发育的理解的一个基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。我们的建议旨在克服这些限制，利用磁共振成像（MRI）为基础的方法。 具体来说，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动物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伤机制相关的定量解剖和生理参数至关重要。这种新方法利用内源性造影剂来量化胎盘的母体灌注，已在临床前动物模型中得到验证，现在准备过渡到人类应用。因此，本提案的目的是优化用于人类妊娠的内源性对比MR采集协议，调整我们先前开发的用于分析对比度依赖性数据的3D分析工具，以用于对人类中的非对比灌注图进行建模，并确定将在正常和高危人类妊娠中建立妊娠妇女中胎盘灌注的纵向正常方差的基本数据，重点关注吸烟对胎盘功能的环境干扰。 我们提出了一项纵向前瞻性队列研究的300名孕妇在两个网站：OHSU和犹他州大学。所有研究受试者将在整个妊娠期间（妊娠12-16周、26-28周和32-34周）接受三次胎盘MRI扫描，并将在分娩时收集胎盘组织。将根据三个队列的选择标准招募受试者：1）非吸烟者，2）吸烟者和3）不良妊娠结局的高风险。我们的科学方法将使我们能够生成数据，证明整个妊娠期孕妇胎盘灌注的正常变化。我们的内源性对比MRI方案在血管损伤高危女性中的应用（即，吸烟者和有胎盘功能不全病史者）将使我们能够测试这种新技术预测不良临床结果的灵敏度和特异性。这些工具的成功开发将通过创建一种定量确定胎盘灌注同时保留人类胎盘特有的空间和生理特征的方法，显著推进胎盘功能的非侵入性成像。

 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.