Dynamic contrast-enhanced MRI of placental circulation

描述(由申请人提供)：孕妇在怀孕期间肥胖很常见，并与产科、新生儿和儿童风险增加有关。由于全球肥胖症流行以及高卡路里/高脂肪西式饮食(HFD)的供应和消费，孕妇在怀孕期间的营养问题日益受到关注。非人灵长类(NHP)具有与人类胎儿相似的发育个体发育，包括胎盘功能，以及当摄入HFD饮食时的全部代谢性疾病，使其成为可翻译研究的宝贵模型。在这个动物模型中，我们能够区分母亲饮食和代谢健康的相对贡献，这在人类队列中是困难的。我们最近的研究直接将HFD的摄入与子宫胎盘灌注量的减少和胎盘损伤的增加联系在一起，这表明西式饮食可能对肥胖人群中报告的产科和新生儿的不良后果有显着的独立影响。由于胎盘调节从母亲到胎儿的营养交换，它在调节与肥胖孕妇相关的不利产科风险方面发挥着核心作用。目前对胎盘功能的评估，无论是临床还是研究，都受到无法将胎盘灌注与胎盘病理和营养物质转运联系起来的限制。我们的目标是在我们的NHP模型中了解胎盘血流改变对胎盘发育和脂质运输的影响。我们开发了一种新的动态增强磁共振成像(DCE-MRI)技术，它可以量化胎盘血流量直接流向胎盘的转移单位-子叶。我们建议使用DCE-MRI，并辅之以单独鉴定的子叶的体外脂质运输分析，来关联血流和脂质摄取。其次，我们将同时利用对比增强超声(CE-US)作为DCE-MRI的补充成像技术，可以更容易地在临床环境中实施，作为胎盘功能障碍的诊断工具。新鲜的胎盘绒毛外植体将用于放射性标记脂肪酸摄取研究。正如DCE-MRI和CE-US所定量的那样，每个子叶中的脂肪ACI摄取将与胎盘的血流灌注相关。胎盘组织将被评估是否有缺血和功能不全的病理证据。此外，我们还将确定从单独取样的子叶中分离的胎盘匀浆中脂肪酸运输途径的成分，并测量母体和胎儿的甘油三酯和非酯化脂肪酸的水平。总之，我们的新方法在一个生理相关的动物模型中使用了先进的成像技术，将胎盘血流与重要的功能终点联系起来，并证明了使用先进的成像技术来识别胎盘功能不全的可行性，无论是基础科学还是临床应用。

DESCRIPTION (provided by applicant): Maternal obesity during pregnancy is common and is associated with increased obstetric, neonatal, and childhood risks. Of growing concern is maternal nutrition during pregnancy due to the global obesity epidemic and the availability and consumption of a high calorie/high fat Western style diet (HFD). The nonhuman primate (NHP) shares developmental ontogeny similar to human fetuses including placental function, and the full spectrum of metabolic disease when placed on a HFD diet making it an invaluable model for translatable studies. In this animal model we are able to distinguish the relative contribution of maternal diet and metabolic health, something that is difficult in human cohorts. Our recent studies directly link HFD consumption in this well characterized NHP model with a reduction in uteroplacental perfusion and increased placental injury suggesting that a Western style diet may have a significant independent impact on the adverse obstetric and neonatal consequences reported in the obese human population. Since the placenta regulates nutrient exchange from mother to fetus, it occupies a central role in mediating the adverse obstetric risks associated with the obese gravidae. Current assessments of placental function, both clinical and research are limited by an inability to link placental perfusion with placental pathology and nutrient transport. Our objectives are to understand the consequences of altered placental blood flow on placental development and lipid transport in our NHP model. We have developed a novel Dynamic Contrast Enhanced-MRI (DCE-MRI) technique that quantifies placental blood flow directly to the transfer unit of the placenta, the cotyledon. We propose to use DCE-MRI, complemented by in vitro assays of lipid transport in individually identified cotyledons, to correlate blood flow with lipid uptake. Secondarily, we will simultaneously utilize Contrast Enhanced-Ultrasound (CE-US) as a complementary imaging technique to DCE-MRI that can be more readily implemented in the clinical setting as a diagnostic tool for placental dysfunction. Fresh placental villous explants will be used for radiolabeled fatty acid uptake studies. Fatty aci uptake in each cotyledon will be correlated with placental perfusion as quantified by DCE-MRI and CE-US. Placental tissue will be assessed for pathological evidence of ischemia and insufficiency. In addition, we will characterize components of the fatty acid transport pathway in placental homogenate isolated from individually sampled cotyledons, and measure maternal and fetal levels of triglycerides and nonesterified fatty acids. In summary, our novel approach uses advanced imaging in a physiologically relevant animal model to link placental perfusion with a vital functional endpoint, and demonstrate the feasibility of using advanced imaging techniques to identify placental insufficiency for both basic science and clinical implementation.