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.

项目总结/摘要：在人类妊娠期间，胎盘滋养层细胞取代光滑的 肌肉、血管内皮（VE）细胞和子宫螺旋动脉（SA）壁的弹性组织， 底蜕膜（DB），将这些动脉转化为具有可扩张壁/扩大的高容量血管 促进血液流向绒毛间隙（IVS）和胎儿发育。子宫动脉缺损 重塑（UAR）是胎儿生长受限（FGR）、先兆子痫（PE）和早产的基础， 新生儿发病率/死亡率。检测孕早期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。一个主要 广泛使用的多普勒的局限性在于，它不能可靠地检测到早于第二次UAR的受损UAR。 三个月，并受到“模糊”伪影、混叠和信号丢失的限制。我们已经证明， 狒狒妊娠早期的雌二醇（E2）水平抑制UAR，导致母体VE功能障碍， FGR。我们的狒狒翻译模型提供了一个新的实验范式，在其中建立实时 成像技术来评估SA灌注作为UAR的指标。超声造影 (CEU)/微泡（MB）成像用于在男性和非妊娠女性中诊断性地评估血流， 但目前不能在怀孕到足月的孕妇中进行。我们建议CEU/MB提供 作为结构和功能的SA内的体积/管腔面积和流量的实时声学快照 UAR的指标。B超血流是一种4D非多普勒技术，我们首次 在B流上叠加M模式，以出色的空间分辨率量化SA直径和壁 膨胀性本研究的总体目标是建立CEU/MB和B-flow/M模式作为新的原型， 分别量化SA体积/流量和直径/扩张性，作为互补的结构和功能 正常和异常妊娠的UAR指数。目标1将检验CEU/MB和B- 血流/M模式提供了最先进的方法来量化SA灌注和直径/扩张性， UAR指数，在未处理或用抑制UAR的E2处理的狒狒中。母体、胎盘和胎儿 在CEU/MB后，将确定狒狒的生理参数，以建立 将CEU/MB应用于人类妊娠。目标2将测试超声B流/M模式的假设 提供了一种新的方法来量化SA直径/扩张性，作为UAR的结构和功能指标， 作为人类异常妊娠的早期标志。本研究的完成时间为 预计将建立创新的成像方法，这将导致更有效的预测和管理 由UAR缺陷引起的人类不良妊娠。

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