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

项目摘要 胎盘从母体血液循环中提供氧气和营养物质， 胎儿循环中的废物，对胎儿发育至关重要， 母体和胎儿胎盘灌注。开发非侵入性工具的临床益处 胎盘功能的评估是巨大的。包括正确诊断胎盘功能不全 作为胎儿生长受限的原因，并检测到胎儿氧可用性降低， 以防止神经损伤这项建议结合了两个调查小组的长处 与互补的方法，并建立在我们以前的胎盘磁共振成像（MRI） 成绩具体来说，我们的团队使用怀孕的非人类灵长类动物（NHP）， 胎盘功能的空间建模方法，结合动态对比增强（DCE）MRI， T2* 弛豫映射的验证。我们的团队还开发了新的MR成像和数据建模 方法采用同步扩散编码（IVIM-DWI）和多回波自旋回波采集。初始临床 这些方法的应用显示了分别询问母-胎盘和胎儿的潜力， 胎盘循环-这是一个重要的标志，用于确定胎儿缺氧。本报告的总体目标 建议是开发多模态MRI和建模方法，并在临床相关NHP中进行验证 模型，以提供评估胎盘健康的可靠定量方法。 我们工作的重要性来自于结合多种对比技术产生的数据， 提供胎盘灌注和氧饱和度的估计值，采用金标准氧测量 水平在胎儿和分娩后测量胎盘血管结构在我们的翻译NHP 模型通过利用胎盘血流和功能的已建立和新的计算模型， 先进的方法和丰富的数据的独特组合将使我们能够测量氧气传输的特性， 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， 胎儿氧合（Aim 2）。这些方法的结合将使我们能够量化和验证 在一系列相关变量中，对人类胎盘氧灌注和运输最感兴趣的变量 胎儿血氧水平我们的建模方法的验证将显着提高区分能力 MRI在分层妊娠中的应用，其中胎盘功能不全和胎儿缺氧被怀疑。重要的是我们 我们已经在NHP模型中获得了初步数据，这些数据证明了我们所采用的方法的可行性。 求婚预期工作的成功完成将产生一组新的非对比度功能和 在适当的动物模型中验证的结构MRI胎盘汇总统计量，可以转换为 用于早期识别妊娠并发症风险的人体研究。

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.