Contrast-Enhanced/Microbubble and B-Flow/M-Mode Ultrasonography to Quantify Uteroplacental Perfusion During Baboon and HumanPreganancy

对比增强/微泡和 B 流/M 型超声检查可量化狒狒和人类怀孕期间的子宫胎盘灌注

• 批准号: 10000189
• 负责人: Ozhan Mehmet Turan
• 金额: $ 51.38万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000189
• 关键词: 3-Dimensional; Acoustics; Area; Arteries; Beds; Biopsy; Blood Vessels; Blood flow; Caliber; Characteristics; Clinical; Color; Decidua Basalis; Defect; Development; Diagnosis; Diagnostic; Dimensions; Disease; Doppler Ultrasonography; Doppler Ultrasound; Dropout; Elastic Tissue; Estradiol; Etiology; Fetal Development; Fetal Growth Retardation; Fetus; First Pregnancy Trimester; Future; Genes; Goals; Heart Abnormalities; Histologic; Human; Image; Imaging technology; Impairment; In Situ; Invaded; Laboratories; Laboratory Animals; Latex; Lead; Measures; Methods; Microbubbles; Mission; Modeling; Morphologic artifacts; National Institute of Child Health and Human Development; Organ; Papio; Perfusion; Peripheral; Physiological; Placenta; Placenta Diseases; Placentation; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Primates; Process; Research; Resistance; Resolution; Safety; Second Pregnancy Trimester; Signal Transduction; Smooth Muscle; Spiral Artery of the Endometrium; Structure; Technology; Termination of pregnancy; Testing; Time; Translating; Ultrasonography; Uterus; Vascular Endothelial Cell; Woman; contrast enhanced; cytotrophoblast; early onset; fetal; fetal blood; imaging approach; imaging modality; indexing; innovation; maternal hypertension; men; mortality; neonatal morbidity; nonhuman primate; novel; novel imaging technology; novel strategies; prototype; real-time images; translational model; trophoblast; vascular endothelial dysfunction

PROJECT SUMMARY/ABSTRACT: During human pregnancy, placental trophoblasts replace the smooth muscle, vascular endothelial (VE) cells, and elastic tissue of the walls of the uterine spiral arteries (SA) within the decidua basalis (DB), transforming these arteries into high-capacity vessels with distensible walls/enlarged lumens to promote blood flow to the intervillous space (IVS) and fetal development. A defect in uterine artery remodeling (UAR) underlies fetal growth restriction (FGR), preeclampsia (PE) and pre-term birth, which result in neonatal morbidity/mortality. Non-invasive real-time methods to detect impaired UAR in the first trimester would be highly advantageous to more effectively diagnose and treat PE, preterm birth and FGR. A major limitation of widely used Doppler is that it does not reliably detect impaired UAR earlier than the second trimester and is limited by “blooming” artifacts, aliasing, and signal dropout. We have shown that elevating estradiol (E2) levels in early baboon pregnancy suppressed UAR and caused maternal VE dysfunction and FGR. Our baboon translational model provides a novel experimental paradigm in which to establish real-time imaging technologies to assess SA perfusion as an index of UAR. Contrast-enhanced ultrasonography (CEU)/microbubble (MB) imaging is used to assess blood flow diagnostically in men and nonpregnant women, but currently cannot be performed in pregnant women carrying to term. We propose that CEU/MB provides a real-time acoustic snapshot of the volume/lumenal area of and flow within the SA as structural and functional indices of UAR. Ultrasound B-flow is a 4D non-Doppler technology and we have for the first time superimposed M-mode on B-flow to quantify with exceptional spatial resolution SA diameter and mural distensibility. The overall goal of this study is to establish CEU/MB and B-flow/M-mode as novel prototypes to quantify SA volume/flow and diameter/distensibility, respectively, as complementary structural and functional indices of UAR across normal and abnormal pregnancy. Aim 1 will test the hypothesis that CEU/MB and B- flow/M-mode provide state-of-the-art approaches to quantify SA perfusion and diameter/distensibility, as indices of UAR, in baboons untreated or treated with E2 which suppresses UAR. Maternal, placental and fetal physiological parameters will be ascertained in baboons after CEU/MB to establish safety standards for the application of CEU/MB to human pregnancy. Aim 2 will test the hypothesis that ultrasound B-flow/M-mode provides a novel method to quantify SA diameter/distensibility, as structural and functional indices of UAR, across normal pregnancy and as an early marker of abnormal human pregnancy. Completion of this study is expected to establish innovative imaging methods that will lead to more effective prediction and management of adverse human pregnancy arising from defective UAR.

项目摘要/摘要：在人类怀孕期间，胎盘滋养层细胞取代了光滑的 子宫螺旋动脉(SA)壁的肌肉、血管内皮细胞和弹性组织 蜕膜(DB)，将这些动脉转化为具有可扩张壁的高容量血管/放大 管腔促进血液流向绒毛间隙(IVS)和胎儿发育。子宫动脉的缺陷 重构(UAR)是胎儿生长受限(FGR)、先兆子痫(PE)和早产的基础，从而导致 新生儿发病率/死亡率。妊娠早期UAR受损的无创实时检测方法 对于更有效地诊断和治疗PE、早产和FGR将是非常有利的。一位少校 广泛使用的多普勒的局限性是它不能可靠地检测到早于秒的UAR受损 三个月，并受到“开花”伪影、混叠和信号丢失的限制。我们已经证明，提升 怀孕早期的雌二醇(E2)水平抑制UAR，并导致母体VE功能障碍和 FGR。我们的狒狒翻译模型提供了一种新的实验范式，在其中建立了实时 影像技术评估SA血流灌注作为UAR的一个指标。超声造影 (CEU)/微泡(MB)成像用于诊断性地评估男性和未怀孕女性的血流， 但目前不能在怀孕到足月的孕妇身上进行。我们建议CEU/MB提供 作为结构和功能的SA的体积/腔面积和内部血流的实时声学快照 UAR指数。超声B-Flow是一种4D非多普勒技术，我们首次 将M型超声叠加到B型血流上，以获得卓越的空间分辨率、SA直径和壁画 膨胀性。这项研究的总体目标是建立CEU/MB和B-Flow/M-模式作为新的原型 将SA体积/流量和直径/膨胀性分别量化为互补的结构和功能 正常妊娠和异常妊娠的UAR指数。目标1将检验CEU/MB和B- Flow/M模式提供了最先进的方法来量化SA灌注和直径/扩张性，如 在未经处理或用抑制UAR的E2处理的狒狒中，UAR的指标。母体、胎盘和胎儿 将在CEU/MB后确定狒狒的生理参数，以建立安全标准 CEU/MB在人类妊娠中的应用目标2将检验超声B-Flow/M-模式的假设 提供了一种新的方法来量化SA直径/膨胀性，作为UAR的结构和功能指标， 在正常妊娠和异常妊娠的早期标志。这项研究的完成情况是 有望建立创新的成像方法，从而实现更有效的预测和管理 由UAR缺陷引起的人类不良妊娠。