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

项目总结 胎盘从母体循环中提供氧气和营养的能力，并消除 来自胎儿循环的废物，对胎儿发育至关重要，并依赖于足够的 母体和胎儿胎盘的灌流。开发体内无创工具的临床益处 对胎盘功能的评估是巨大的。其中包括正确诊断胎盘功能不全。 作为胎儿生长受限的原因，以及检测到胎儿氧气供应减少，允许分娩 被加快以防止神经损伤。这项建议结合了两个调查小组的优势 补充方法学，并建立在我们之前的胎盘磁共振成像(MRI)的基础上 成就。具体地说，我们团队对怀孕的非人灵长类动物(NHP)的使用使得发育 结合动态增强磁共振成像(DCE)的胎盘功能空间建模方法研究 T2*松弛图的验证我们的团队还开发了新颖的磁共振成像和数据建模 方法采用同步扩散编码(IVIM-DWI)和多回波自旋回波(MultiECHO)采集。初期临床 这些方法的应用显示了将母体胎盘和胎儿分开审问的可能性。 胎盘循环--这是识别胎儿缺氧的关键标志。这样做的总体目标是 建议开发多模式磁共振成像和建模方法，并在临床相关的NHP中进行验证 模型，为评估胎盘健康提供可靠的量化方法。 我们工作的意义来自于将由多种对比技术生成的数据组合在一起 提供胎盘血流和血氧饱和度的估计值，并提供氧气的金标准测量 我们翻译的NHP的胎儿水平和产后胎盘血管结构的测量 模特。通过利用已建立的和新的胎盘血流和功能的计算模型，我们的 先进的方法和丰富的数据的独特结合将使我们能够测量氧转移到 胎儿血管系统(目标1)。这些定量参数的生理学解释将进一步 在母体氧合受控变化的研究中得到验证，同时测量 胎儿氧合(目标2)。这些方法的结合将使我们能够量化和验证 对人体胎盘氧气灌流和转运最感兴趣的变量 胎儿血氧水平。对我们的建模方法的验证将显著提高判别能力 MRI在怀疑胎盘功能不全和胎儿缺氧的分层妊娠中的应用。重要的是，我们 在我们的NHP模型中获得了初步数据，证明了该方法的可行性 求婚。预期工作的成功完成将产生一套新颖的非对比功能和 结构磁共振胎盘概要统计，在适当的动物模型中验证，可以翻译 到人体研究，以便及早识别有并发症风险的妊娠。

PROJECT SUMMARY The capacity of the placenta to supply oxygen and nutrients from the maternal circulation, and eliminate waste products from the fetal circulation, is critical for fetal development and is dependent on adequate maternal- and fetal-placental perfusion. The clinical benefits of developing noninvasive tools for the in vivo assessment of placental function are tremendous. They include the proper diagnosis of placental insufficiency as a cause of fetal growth restriction, and detection of decreased fetal oxygen availability, allowing delivery to be expedited to prevent neurological damage. This proposal combines the strengths of two investigative teams with complementary methodologies, and builds upon our prior placental Magnetic Resonance Imaging (MRI) achievements. Specifically, our team’s use of the pregnant nonhuman primate (NHP) has allowed development of spatial modelling methods of placental function integrating dynamic contrast enhanced (DCE) MRI for validation of T2* relaxation mapping. Our team have also developed novel MR imaging and data modeling methods with simultaneous diffusion-encoded (IVIM-DWI) and multiecho spin-echo acquisitions. Initial clinical application of these methods showed the potential to separately interrogate the materno-placental and feto- placental circulations – this is a critical marker for identifying fetal hypoxia. The overall objective of this proposal is to develop multi-modal MRI and modelling approaches, validated in a clinically relevant NHP model, to provide robust quantitative methods for assessing placental health. The significance of our work derives from combining data generated from multiple contrast techniques that provide estimates of placental perfusion and oxygen saturation, with gold-standard measurement of oxygen level in the fetus and post-delivery measurement of the placental vascular structure in our translational NHP model. By leveraging established and new computational modeling of placental blood flow and function, our unique combination of advanced methods and rich data will let us measure the properties of oxygen transfer to the fetal vasculature (Aim 1). The physiological interpretation of these quantitative parameters will be further validated in studies subject to controlled changes in maternal oxygenation accompanied by measurement of fetal oxygenation (Aim 2). The combination of these methodologies will allow us to quantify and validate the variables that are of most interest to human placenta oxygen perfusion and transport over a range of relevant fetal oxygen levels. The validation of our modeling methods will significantly improve the discriminatory power of MRI in stratifying pregnancies where placental insufficiency and fetal hypoxia is suspected. Importantly, we have acquired preliminary data in our NHP model that demonstrates the feasibility of the approach we are proposing. Successful completion of the intended work will yield a set of novel non-contrast functional and structural MRI placental summary statistics, validated in an appropriate animal model, which can be translated to human studies for early identification of pregnancies at-risk for complications.