Applying Diffusion Basis Spectrum Imaging to Characterize Human Placenta Immuno-response during normal term and preterm pregnancies

摘要/摘要 早产的一个重要原因是免疫渗入胎盘。虽然胎盘免疫 反应很可能在分娩之前很久就开始了，目前还没有可用的技术允许在体内进行实时 妊娠期间胎盘免疫反应的评估。因此，临床医生的能力有限。 检测胎盘炎症或进行干预，以减少免疫反应和预防早产 送货。此R01应用程序建议开发一种新的、非侵入性的人类胎盘免疫成像 (PII)技术，它将能够安全地实时评估人类胎盘炎症，并对 符合RFA-HD-18-003：超越标准评估：应用新工具评估人类 胎盘结构和功能的实时监测。PII将基于扩散磁共振成像 (MRI)技术称为扩散基谱成像，可以对大脑进行非侵入性成像和量化 在动物模型和人类患者中多发性硬化症的炎症。PII的发展必须采取 考虑到人的胎盘与动物的胎盘有很大的不同，而且是一种非常 在整个怀孕期间动态变化的器官。解剖和潜在的病理复杂性和 胎盘的异质性产生了大脑中不存在的强烈背景噪音干扰，使 识别和提取胎盘炎症的特异性信号更具挑战性。要解决这个问题 技术挑战，该提案将通过使用三种技术开发专门用于人类应用的PII 不同的临床队列：那些早产风险低的人(目标1)，以及那些早产风险高的人 对预防早产的治疗有反应或无反应(目标2和3)。除了……之外 在怀孕的两个时间点(目标2和目标3)或三个时间点(目标1)对这些妇女进行PII，此建议 包括对母体血液中免疫因子和长非编码RNA的测量，以及组织学 分娩时获取的胎盘样本中炎性细胞的特征。完成这些目标 1)将产生一个完全发展的PII系统，2)通过胎盘的组织病理学评估来完善PII 和系统免疫反应的测量，3)定义胎盘免疫反应的特征 健康、足月妊娠，4)确定有风险的妊娠的胎盘免疫反应 早产，以及开始揭示与黄体酮成败相关的免疫信号 治疗。因为PII将需要已经得到食品和药物管理局批准的MRI序列 它的安全性和极大的可及性将使其迅速扩展到临床试验或临床 人口。

Summary/Abstract An important cause of preterm labor is immune infiltration into the placenta. Although the placental immune response likely starts long before delivery, no technique currently available permits in vivo, real-time assessment of placental immune responses during pregnancy. As a result, clinicians have limited ability to detect placental inflammation or intervene so as to reduce the immune response and prevent preterm delivery. This R01 application proposes to develop a novel, noninvasive human placental immune imaging (PII) technique, which will be able to safely assess human placental inflammation in real time, responding to RFA-HD-18-003: Moving Beyond Standard Assessments: Applying Novel Tools to Assess Human Placental Structure and Function in Real Time. PII will be based on a diffusion magnetic resonance imaging (MRI) technique called diffusion basis spectrum imaging, which can noninvasively image and quantify brain inflammation in multiple sclerosis in both animal models and human patients. Development of PII must take into account the fact that the human placenta is quite different from animal placentas and is a very dynamically changing organ throughout pregnancy. The anatomic and potential pathological complexity and heterogeneity of the placenta create strong background noise interference not present in the brain, making it more challenging to identify and extract the signals specific to placental inflammation. To address this technical challenge, this proposal will develop PII specifically for human applications by making use of three distinct clinical cohorts: those at low risk of preterm birth (Aim 1), and those at high risk of preterm birth who either respond or fail to respond to treatment to prevent preterm birth (Aims 2 and 3). In addition to performing PII on these women at two (Aims 2 and 3) or three (Aim 1) time points in pregnancy, this proposal includes measurement of immune factors and long non-coding RNAs in maternal blood, and histological characterization of inflammatory cells in placenta samples obtained at delivery. Completion of these aims will 1) yield a fully developed PII system, 2) refine PII through histopathological assessments of placentas and measures of systemic immune responses, 3) define the placental immune responses characteristic of healthy, term pregnancy, 4) identify placental immune responses characteristic of pregnancies at risk of preterm birth, and 5) begin to reveal immune signatures associated with success and failure of progesterone treatment. Because PII will require MRI sequences that are already approved by the Food and Drug Administration, its safety and great accessibility will allow it to be rapidly extended to clinical trials or clinical populations.