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，发育中胎儿的子宫内环境会影响健康结果，其影响范围远远超出围产期，直至成年。胎盘发育异常与几乎所有不良产科结局有关，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之间的媒介物很重要，但它仍然是人们最不了解的人体器官。充足的血流和氧气输送是胎盘功能和胎儿生长的主要决定因素。缺乏方便的成像方式 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。 胎盘特异性MRI方法的发展所面临的挑战之一是灵长类动物胎盘血管系统的复杂结构。在过去的5年中，我们已经利用非人灵长类动物（NHP），它与人类共享包括胎盘结构和功能在内的发育特征，开发了一种动态对比增强MRI（DCE-MRI）方法，该方法可以量化每个螺旋动脉的胎盘血流。尽管我们最近证明了在DCE-MRI期间母体给予钆基造影剂导致的胎儿钆暴露水平极低，但在对妊娠患者进行成像时应格外小心，因此开发不依赖于造影剂给药的功能性MRI方法具有高度相关性。重要的是，我们已经在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。我们建议使用我们的临床相关NHP模型进行非对比MRI序列开发和优化。在这些研究中同时使用DCE-MRI将使我们能够利用我们的胎盘灌注的对比度依赖性定量测量作为非对比建模的基准。我们建议将我们的研究转移到人类受试者中，以实施新开发的MR成像程序并评估其临床用途。开发MRI方案用于胎盘血流和氧合的体内评估的潜在临床益处是巨大的;了解正常胎盘功能将改善妊娠的临床监测，允许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。如果所提出的研究是成功的，那么我们将开发出一种协议，允许快速，可重复的非造影剂介导的手段可视化和定量胎盘灌注和氧合。

 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.