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: 10224287
• 负责人: Ozhan Mehmet Turan
• 金额: $ 50.35万
• 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/10224287
• 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，胎盘滋养层取代平滑肌细胞。 子宫螺旋动脉 (SA) 内的肌肉、血管内皮 (VE) 细胞和弹性组织 基底蜕膜 (DB)，将这些动脉转变为具有可扩张壁/扩大的高容量血管 促进血液流向绒毛间隙 (IVS) 和胎儿发育的子宫动脉缺陷。 重塑（UAR）是胎儿生长受限（FGR）、先兆子痫（PE）和早产的基础，其导致 用于检测妊娠早期 UAR 受损的非侵入性实时方法。 将非常有利于更有效地诊断和治疗PE、早产和FGR A重大。 广泛使用的多普勒的局限性在于它不能比第二个更早可靠地检测到受损的 UAR 三个月期，并受到“开花”伪影、混叠和信号丢失的限制，我们已经证明了这一点。 狒狒妊娠早期的雌二醇 (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颖的实验范式，可以在其中建立实时模型。 评估 SA 灌注作为 UAR 指标的成像技术。 (CEU)/微泡 (MB) 成像用于诊断性评估男性和非孕妇的血流， 但目前不能在足月孕妇中进行，我们建议 CEU/MB 提供一种方法。 SA 内的体积/腔面积和流量的实时声学快照作为结构和功能 UAR 超声 B 流指标是我们首次采用的 4D 非多普勒技术。 在 B 流上叠加 M 模式，以卓越的空间分辨率对 SA 直径和壁画进行量化 本研究的总体目标是建立 CEU/MB 和 B-flow/M-mode 作为新颖的原型。 SA 分别量化体积/流量和直径/扩张性，作为结构和功能的补充 目标 1 将检验 CEU/MB 和 B- 的假设。 流量/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 未治疗或用 E2 治疗的狒狒的 UAR 指数，E2 可抑制母体、胎盘和胎儿的 UAR。 CEU/MB 后将确定狒狒的生理参数，以制定狒狒的安全标准 CEU/MB 在人类妊娠中的应用 目标 2 将检验超声 B 流/M 模式的假设。 提供了一种量化 SA 直径/扩张性的新方法，作为 UAR 的结构和功能指标， 跨越正常妊娠并作为人类异常妊娠的早期标志。 期望建立创新的成像方法，从而实现更有效的预测和管理 由有缺陷的 UAR 引起的不良人类妊娠。