Dynamic contrast-enhanced MRI of placental circulation

描述（由申请人提供）：妊娠期母亲肥胖很常见，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热量/高脂肪西式饮食（HFD）的可获得性和消费，越来越令人关注的是怀孕期间的孕产妇营养。非人灵长类动物（NHP）的发育个体发生与人类胎儿相似，包括胎盘功能，以及在HFD饮食中出现的全谱代谢疾病，使其成为可翻译研究的宝贵模型。在这个动物模型中，我们能够区分母体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联系HFD消费在这个良好的特点NHP模型子宫胎盘灌注减少和胎盘损伤增加，表明西式饮食可能有一个显着的独立影响不良产科和新生儿的后果报告在肥胖人群。由于胎盘调节母体与胎儿之间的营养交换，因此它在调节与肥胖孕妇相关的不良产科风险方面起着核心作用。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学和营养转运联系起来的限制。我们的目标是了解胎盘血流改变对胎盘发育和脂质转运的影响。我们已经开发了一种新的动态对比增强MRI（DCE-MRI）技术，定量胎盘血流直接到胎盘的传输单元，子叶。我们建议使用DCE-MRI，辅以体外测定脂质转运在个别确定的子叶，相关的血流与脂质摄取。其次，我们将同时利用造影增强超声（CE-US）作为DCE-MRI的补充成像技术，该技术可以更容易地在临床环境中作为胎盘功能障碍的诊断工具实施。新鲜胎盘绒毛外植体将用于放射性标记脂肪酸摄取研究。每个子叶中的脂肪酸摄取将与胎盘灌注相关，如通过DCE-MRI和CE-US定量的。将评估胎盘组织的缺血和功能不全的病理学证据。此外，我们将表征胎盘匀浆中的脂肪酸转运途径的成分，从单独采样的子叶分离，并测量母体和胎儿的甘油三酯和非酯化脂肪酸水平。总之，我们的新方法在生理相关的动物模型中使用先进的成像技术将胎盘灌注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识别胎盘功能不全的可行性，用于基础科学和临床实施。

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.