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

用于胎盘灌注和氧输送体内评估的 MR 成像方法的开发和验证

• 批准号: 10583121
• 负责人: Andrew Melbourne
• 金额: $ 56.08万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-20 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583121
• 关键词: Achievement; Animal Model; Blood; Blood Vessels; Blood Volume; Blood flow; Blood gas; Characteristics; Chronic; Circulation; Clinical; Clinical Management; Collaborations; Complex; Computer Models; Coupling; Data; Dependence; Detection; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Early identification; Fetal Development; Fetal Growth Retardation; Fetoplacental Circulation; Fetus; Future; Health; Human; Image; Individual; Injury; Lateral; Left; Link; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methodology; Methods; Modeling; Nervous System Trauma; Nutrient; Oxygen; Perfusion; Physiological; Physiology; Placenta; Placental Circulation; Placental Insufficiency; Placentation; Positioning Attribute; Pre-Eclampsia; Pregnancy; Premature Labor; Primates; Property; Relaxation; Research; Risk; Role; Sheep; Side; Structure; Structure of placental cotyledon; Study Subject; Supination; Techniques; Tissues; Translating; Validation; Variant; Waste Products; Work; adverse outcome; clinical application; clinical diagnostics; clinically relevant; contrast enhanced; data acquisition; data analysis pipeline; data modeling; fetal; fetal blood; fetus hypoxia; hemodynamics; human study; imaging approach; imaging biomarker; imaging capabilities; imaging modality; improved; in utero; in vivo; interest; member; multimodality; nonhuman primate; novel; obstetric outcomes; offspring; oxygen transport; pregnant; prevent; quantitative imaging; response; statistics; stillbirth; tool; tool development

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.

项目概要 胎盘从母体循环中提供氧气和营养物质并排除毒素的能力 胎儿循环中产生的废物对于胎儿发育至关重要，并且依赖于足够的 开发体内无创工具的临床益处。 胎盘功能的评估是巨大的，其中包括胎盘功能不全的正确诊断。 作为胎儿生长受限的原因，并检测胎儿氧气供应量减少，从而允许分娩 该提案结合了两个调查小组的优势。 具有互补的方法，并建立在我们之前的胎盘磁共振成像 (MRI) 的基础上 具体来说，我们的团队使用怀孕的非人类灵长类动物（NHP）实现了发育。 整合动态对比增强 (DCE) MRI 的胎盘功能空间建模方法 T2* 松弛映射的验证我们的团队还开发了新颖的 MR 成像和数据建模。 具有同时扩散编码（IVIM-DWI）和多回波自旋回波采集的方法初始临床。 这些方法的应用显示了分别询问母体胎盘和胎儿的潜力 胎盘循环——这是识别胎儿缺氧的关键标志物。 建议开发多模态 MRI 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稳健的定量方法。 我们工作的意义在于结合多种对比技术生成的数据，这些数据 提供胎盘灌注和氧饱和度的估计，以及氧的金标准测量 在我们的转化 NHP 中胎儿水平和胎盘血管结构的产后测量 通过利用已建立的和新的胎盘血流和功能计算模型，我们的模型。 先进方法和丰富数据的独特结合将使我们能够测量氧气转移到 胎儿脉管系统（目标 1）将进一步对这些定量参数进行生理解释。 在受控母体氧合变化并伴随测量的研究中得到验证 这些方法的结合将使我们能够量化和验证胎儿氧合。 在一系列相关的范围内对人类胎盘氧灌注和运输最感兴趣的变量 我们的建模方法的验证将显着提高辨别能力。 重要的是，我们对怀疑胎盘功能不全和胎儿缺氧的妊娠进行分层进行 MRI 分析。 已经在我们的 NHP 模型中获得了初步数据，证明了我们所采用的方法的可行性 成功完成预期工作将产生一套新颖的非对比功能和 结构 MRI 胎盘汇总统计数据，在适当的动物模型中得到验证，可以翻译 用于早期识别有并发症风险的妊娠的人体研究。