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: 10471256
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10471256
• 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; ultrasound; 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，Placenal滋养细胞取代平滑 肌肉，血管内皮（VE）细胞和子宫螺旋动脉壁的弹性组织（SA） canceua bassalis（db），将这些动脉转化为具有不可辨别的墙/扩大的高容量视频 流明促进血液流向介绍空间（IVS）和胎儿发育。子宫动脉缺陷 重塑（UAR）是胎儿生长限制（FGR），先兆子痫（PE）和术前出生的基础，结果 在新生儿发病率/死亡率中。在头三个月检测UAR受损的非侵入性实时方法 对于更有效地诊断和治疗PE，早产和FGR将是有利的。专业 广泛使用多普勒的限制是，它不能比第二个更早可靠地检测到UAR受损 孕期，受“开花”文物，混叠和信号辍学的限制。我们已经表明了抬高 早期狒狒妊娠的雌二醇（E2）抑制了UAR，并引起母体功能障碍和 FGR。我们的狒狒翻译模型提供了一种新型的实验范式，以建立实时 成像技术将SA灌注评估为UAR指数。对比增强的超声检查 （CEU）/Microbubble（MB）成像用于在男性和未怀孕的女性中诊断出血流， 但是目前无法在任期任期的孕妇中进行。我们建议CEU/MB提供 SA内的体积/流体区域的实时声音快照作为结构和功能 UAR的索引。超声B-Flow是一种4D非多普勒技术，我们首次拥有 在B-Flow上叠加的M模式以量化特殊的空间分辨率SA直径和壁画进行量化 扩张性。这项研究的总体目标是将CEU/MB和B-Flow/M模式建立为新型原型 分别量化SA体积/流量和直径/膨胀性，为完整的结构和功能 UAR的指数在正常和异常妊娠中。 AIM 1将检验CEU/MB和B-的假设 流量/M模式提供了量化SA灌注和直径/扩张性的最先进方法 UAR的索引，在未经治疗或用E2处理的狒狒中，抑制UAR。孕产妇，斑点和胎儿 在CEU/MB之后，将在狒狒中确定物理参数，以建立安全标准 将CEU/MB应用于人类怀孕。 AIM 2将测试超声B流/M模式的假设 提供了一种新颖的方法来量化SA直径/扩张性，作为UAR的结构和功能指数， 在正常怀孕和作为人类怀孕异常的早期标记中。这项研究的完成是 期望建立创新的成像方法，从而导致更有效的预测和管理 因UAR缺陷引起的人类妊娠不良妊娠。

项目成果

B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

• DOI: 10.1002/uog.23753
• 发表时间: 2022-03
• 期刊: ULTRASOUND IN OBSTETRICS & GYNECOLOGY
• 影响因子: 7.1
• 作者: Turan, O. M.;Babischkin, J. S.;Aberdeen, G. W.;Turan, S.;Harman, C. R.;Pepe, G. J.;Albrecht, E. D.
• 通讯作者: Albrecht, E. D.

Novel Technologies for Target Delivery of Therapeutics to the Placenta during Pregnancy: A Review.

• DOI: 10.3390/genes12081255
• 发表时间: 2021-08-17
• 期刊: Genes
• 影响因子: 3.5
• 作者: Pepe GJ;Albrecht ED
• 通讯作者: Albrecht ED