Quantitative Ultrasound for Assessment of Placental Structure During the Development of Preeclampsia

项目摘要 先兆子痫缺乏有效的治疗方法，部分原因是我们无法检测到胎盘的改变， 组织微结构作为异常胎盘发育的指标。本申请提出了一种MPI 将由纽约州纽约的Weill Cornell Medicine（WCM）和杜兰大学进行的合作研究 (TU)在新奥尔良，洛杉矶。拟议项目是对人类胎盘项目PAR-22-236的响应 并寻求开发一种新的超声方法，用于“安全，实时和非侵入性”评估“ 人类胎盘在怀孕期间的发育”。我们的长期目标是开发成像工具， 改善先兆子痫妇女预后。本提案的总体目标是， 验证定量超声（QUS）检测胎盘微结构变化并将其与 先兆子痫QUS使用射频（RF）US信号定量表征软组织。我们 假设基于QUS的参数将能够量化微观结构的变化， 先兆子痫的特征在一个强有力的科学前提的指导下，这一假设将通过追求 两个具体目的：1）离体定量改变的人胎盘微结构;和2）评估胎盘微结构的变化。 在已建立的先兆子痫啮齿动物模型中，在体内纵向观察微结构。第一个目标，我们 将开发QUS方法来表征人类胎盘，并测试特定QUS 参数将与离体人先兆子痫患者中改变的血管发育和损伤相关 胎盘，以组织病理学为金标准。第二个目标是检验QUS 参数将与微结构和由于血管系统改变和纤维化引起的变化相关。 降低子宫灌注压的子痫前期大鼠模型。这项工作的预期成果将是 验证QUS衍生参数用于评估胎盘微结构。通过这些成像 方法，我们预期将与胎盘微结构相关的特定QUS参数与 先兆子痫的诊断这一结果将有力地推动将更多的资源用于 QUS的临床转化和体内纵向验证，以早期检测和预测 女性的先兆子痫与此融资机会的目标和HPP的目标相一致， 这项工作将导致开发一种新的先兆子痫风险的即时超声评估， 严重程度，这可以使用诊所中现有的超声系统来完成。

PROJECT SUMMARY A lack of effective treatments for preeclampsia persists due, in part, to our inability to detect altered placental tissue microstructure as an indicator of abnormal placental development. This application proposes a MPI collaborative study to be performed by Weill Cornell Medicine (WCM) in New York, NY and Tulane University (TU) in New Orleans, LA. The proposed project is responsive to the Human Placenta Project PAR-22-236 and seeks to develop a novel ultrasound approach for “safe, real-time, and non-invasive” assessment of “the development … of the human placenta across pregnancy”. Our long-term goal is to develop imaging tools to improve outcomes in women with preeclampsia. The overall objective of this proposal is to develop and validate quantitative ultrasound (QUS) to detect and correlate microstructural alterations in the placenta with preeclampsia. QUS uses radio-frequency (RF) US signals to characterize soft tissues quantitatively. We hypothesize that QUS-based parameters will be capable of quantifying the microstructural changes which characterize preeclampsia. Guided by a strong scientific premise, this hypothesis will be tested by pursing two specific aims: 1) To quantify altered human placental microstructure ex vivo; and 2) To assess placental microstructure longitudinally in vivo in an established rodent model of preeclampsia. Under the first aim, we will develop QUS methods to characterize the human placenta and test the hypothesis that specific QUS parameters will correlate with altered vascular development and injury in the ex vivo human preeclamptic placenta, with histopathology as the gold standard. The second aim will test the hypothesis that QUS parameters will correlate with microstructural and changes due to altered vasculature and fibrosis in the reduced uterine perfusion pressure rat model of preeclampsia. The expected outcome of this work will be the validation of QUS-derived parameters for the assessment of placental microstructure. With these imaging methods, we anticipate correlating specific QUS parameters related to placental microstructure with the diagnosis of preeclampsia. This outcome will strongly motivate the dedication of additional resources for clinical translation and in vivo longitudinal validation of QUS to earlier detect and predict severity of preeclampsia in women. Consistent with the goals of this funding opportunity and the goals of the HPP, this work will lead to the development of a new point-of-care ultrasound assessment of preeclampsia risk and severity, which can be accomplished using the ultrasound systems existing in the clinic.