Development and validation of MR imaging methods for in vivo assessment of placental perfusion and oxygenation

 描述(由申请人提供)：人们普遍认为，发育中的胎儿的宫内环境会影响健康结果，其影响范围远远超出围产期至成年期。胎盘发育异常几乎与所有产科不良结局有关，包括胎儿生长异常、早产和死产。然而，尽管胎盘作为母胎交换的中介很重要，但它仍然是人类最不了解的器官。充足的血流量和氧气供应是胎盘功能和胎儿生长的核心决定因素。缺乏成像方式来促进 对正常和异常胎盘的体内研究阻碍了我们对胎盘血流和氧合的理解。我们建议使用磁共振成像(MRI)技术来克服这些限制。灵长类动物胎盘血管的复杂结构是开发胎盘特异性MRI方法所面临的挑战之一。在过去的5年里，我们利用非人类灵长类动物(NHP)，它与人类共享胎盘结构和功能等发育特征，开发了一种动态增强磁共振成像(DCE-MRI)方法，允许对每条螺旋动脉的胎盘血流量进行量化。虽然我们最近证明，在DCE-MRI期间，孕妇服用基于Gd的造影剂所导致的胎儿Gd暴露水平极低，但在对孕妇进行成像时的高度谨慎使得开发不依赖于造影剂注射的功能性MRI方法具有很高的针对性。重要的是，我们已经在我们的NHP模型中获得了初步数据，证明了我们提出的方法的可行性。我们建议将我们的临床相关的NHP模型用于非对比MRI序列的开发和优化。在这些研究中同时使用DCE-MRI将使我们能够利用我们的对比度依赖的胎盘血流灌注定量测量作为非对比度建模的基准。我们建议将我们的研究转移到人类受试者身上，以实施新开发的磁共振成像程序，并评估其临床应用价值。开发用于活体评估胎盘血流和氧合的MRI方案的潜在临床益处是巨大的；了解正常的胎盘功能将改进对妊娠的临床监测，使早期识别有胎盘功能不全风险的妇女，并促进干预以改善胎儿结局。如果建议的研究成功，那么我们将开发出一种方案，允许快速、可重复性的非造影剂介导的方法可视化和量化胎盘灌注和氧合。

 DESCRIPTION (provided by applicant): It is widely accepted that the in utero environment of the developing fetus influences health outcomes that extend well beyond the perinatal period into adulthood. Aberrant placental development has been linked to virtually every adverse obstetric outcome including abnormalities in fetal growth, preterm delivery and stillbirth. Yet, despite its importance as the mediator between maternal-fetal exchange, the placenta remains the least understood human organ. Adequate blood flow and oxygen delivery are central determinants of placental function and fetal growth. The lack of imaging modalities that facilitate the in vivo study of both normal and abnormal placentas impedes our understanding of placental blood flow and oxygenation. We propose to overcome these limitations using magnetic resonance imaging (MRI) technology. One of the challenges faced in the development of placenta-specific MRI methods is the complex structure of the placental vasculature in primates. Over the past 5 years we have utilized the nonhuman primate (NHP), which shares developmental features including placenta structure and function with humans, to develop a dynamic contrast enhanced MRI (DCE-MRI) method that allows for the quantification of placental blood flow from each spiral artery. Although we recently demonstrated that the level of fetal gadolinium exposure resulting from maternal administration of gadolinium-based contrast reagent during DCE-MRI is extremely low, the abundance of caution when imaging pregnant patients makes it highly pertinent to develop functional MRI methods that do not rely on contrast reagent administration. Importantly, we have acquired preliminary data in our NHP model that demonstrates the feasibility of the approach we are proposing. We are proposing to use our clinically relevant NHP model for non-contrast MRI sequence development and optimization. Simultaneous use of DCE-MRI in these studies will allow us to utilize our contrast dependent quantitative measure of placental perfusion as a benchmark for non-contrast modeling. We propose to transition our studies to human subjects to implement newly developed MR imaging procedures and assess their utility for clinical use. The potential clinical benefits of developing MRI protocols for the in vivo assessment of placental blood flow and oxygenation are tremendous; understanding normal placental function will improve clinical monitoring of pregnancy, permit early identification of women at-risk for placental insufficiency, and facilitate intervention to improve fetal outcome. If the proposed studies are successful, then we will have developed a protocol that allows for rapid, reproducible non-contrast mediated means of visualizing and quantifying both placental perfusion and oxygenation.