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浸润到胎盘。虽然胎盘免疫 反应可能在递送之前很久就开始了，目前没有可用的技术允许在体内，实时 评估妊娠期间的胎盘免疫反应。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，防止早产 交付.该R 01申请提出开发一种新的、非侵入性的人类胎盘免疫成像 (PII)技术，这将能够安全地评估人类胎盘炎症在真实的时间， RFA-HD-18-003：超越标准评估：应用新工具评估人类 胎盘结构和功能在真实的时间。PII将基于扩散磁共振成像 (MRI)一种称为扩散基光谱成像的技术，可以对大脑进行无创成像和量化 在动物模型和人类患者中多发性硬化症的炎症。PII的开发必须 考虑到人类胎盘与动物胎盘非常不同， 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， 胎盘的异质性产生了大脑中不存在的强烈背景噪音干扰， 识别和提取胎盘炎症特异性信号更具挑战性。为了解决这个 技术挑战，该提案将开发专门用于人类应用的PII， 不同的临床队列：早产低风险人群（Aim 1）和早产高风险人群， 对预防早产的治疗有反应或无反应（目标2和3）。除了 在妊娠期间的两个（目标2和3）或三个（目标1）时间点对这些女性进行PII， 包括测量母体血液中的免疫因子和长链非编码RNA，以及组织学 在分娩时获得的胎盘样品中的炎性细胞的表征。实现这些目标 将1）产生完全开发的PII系统，2）通过胎盘的组织病理学评估完善PII 和全身免疫反应的测量，3）定义胎盘免疫反应的特征， 健康、足月妊娠，4）鉴定具有妊娠风险的胎盘免疫应答特征， 早产，和5）开始揭示与孕激素的成功和失败相关的免疫特征 治疗因为PII将需要已经获得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能够迅速扩展到临床试验或临床试验。 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.