3D Umbilical Venous Blood Flow - A New Paradigm for Improving the Assessment of Fetal Growth Restriction.

意义：胎儿生长受限(FGR)是婴儿和终身发病率和 非异常胎儿死亡率。然而，仅靠胎儿生物测量并不能可靠地区分小 胎儿的体型较小，有可能导致不良结局。已经做出了相当大的努力 旨在开发更强大的方法来检测和监测有风险的小胎儿 不利的结果。测量脐静脉血流量(UVBF)的常规方法 使用多普勒测速仪测量2D血管直径一直具有挑战性，因为技术因素 这对常规的临床实践来说是不切实际的。我们将通过使用三维超声测量来解决这个问题 脐静脉血流量(3DUVBF)。该方法将彩色血流多普勒超声与二维阵列相结合 换能器以不需要小血管直径的先验知识的方式来量化体积流量， 多普勒电离角、流速分布或血管几何形状。假设：1)三维UVBF是一种精确的、 测量妊娠期间脐静脉血流的可重复性超声参数；2)参考 将容易地生成3D UVBF的标准，为前瞻性分析提供必要的框架； 3)基于3D UVBF的可预测和进行性循环恶化模式显著发生 与其他小胎儿相比，小胎儿(EFW&lt；10%)的不良结局更常见 胎儿无并发症。初步数据：我们已经显示了3D UVBF%的误差，相对于平均值 对妊娠母羊体外胎动、静脉血流测定，9次测量中有8次≤为10%。 在后来发育的7个胎儿中，有2个发现3D UVBF值低于预期 胎儿宫内发育迟缓或先兆子痫(品特、S等人)。《超声医学杂志》37：1633-1640,2018)。在进一步的重复性研究中， 3DUVBF受试者内和测量内相对标准误差(RSE)分别为12.1±5.9和5.6±1.9 %(均值±标准差)(n=35)。具体目标：我们建议验证3D UVBF，开发3D UVBF 参考标准，并提供了EFW&lt；10%的小胎儿循环变化的详细观察。 在具体目标1中，体外流动体模实验和孕妇的重复性研究将检查 3D UVBF的准确性和重复性。在特定的目标2中，系列超声波扫描将开发出处方 400例正常发育胎儿3D-UVBF参考标准在具体目标3中， 多支血管多普勒测速仪的循环模式和3D UVBF变化将在 1100个小胎儿的预期队列。三维UVBF的附加值及相关的多普勒血流图 在识别有不良围产期结局或新生儿发病率的小胎儿时，将进行检查。成功 执行我们的目标应该建立3D UVBF作为一个可重复的循环参数，它是准确和 早在妊娠前三个月就可用于临床。我们的方法可能会改进对小型 在常规成像预测不良妊娠结局变得明显之前，胎儿。

Significance: Fetal growth restriction (FGR) is an independent predictor of infant and lifelong morbidity and mortality of non-anomalous fetuses. However, fetal biometry alone does not reliably distinguish between small fetuses at risk for poor outcomes from those that are constitutionally small. Considerable efforts have been directed toward developing more robust methods for the detection and monitoring of small fetuses at risk for adverse outcomes. Conventional efforts for measuring umbilical venous blood flow (UVBF), using conventional 2D vessel diameter measurements with Doppler velocimetry, have been challenging due to technical factors that make it impractical for routine clinical practice. We will address this problem by using 3D sonography to measure umbilical venous blood flow (3D UVBF). This approach combines color flow Doppler ultrasound with a 2D array transducer to quantify volume flow in a manner that does not require a priori knowledge of small vessel diameter, Doppler insonation angle, flow velocity profile, or vessel geometry. Hypotheses: 1) 3D UVBF is an accurate and reproducible sonographic parameter for measuring umbilical venous flow throughout gestation; 2) Reference standards for 3D UVBF will be readily generated that provide a necessary framework for prospective analyses; and 3) A predictable and progressive circulatory deterioration pattern, based on 3D UVBF, occurs significantly more frequently among small fetuses (EFW < 10th%) with adverse outcomes when compared to other small fetuses without complications. Preliminary Data: We have shown that the 3D UVBF % error, relative to average measured arterial and venous flow, was ≤ 10% for 8 of 9 measurements in exteriorized fetuses of pregnant ewes. Lower than expected 3D UVBF values were found in 2 of 7 fetuses from human pregnancies that later developed FGR or preeclampsia (Pinter S, et al. J Ultrasound Med 37:1633-1640, 2018). In further reproducibility studies, the 3D UVBF intra-subject and intra-measurement relative standard errors (RSE) were 12.1 ± 5.9 and 5.6 ± 1.9 % (mean ± SD), respectively (n=35). Specific Aims: We propose to validate 3D UVBF, develop 3D UVBF reference standards, and provide detailed observations of circulatory changes in small fetuses with EFW < 10th%. In Specific Aim 1, in-vitro flow phantom experiments and reproducibility studies in pregnant women will examine the accuracy and reproducibility of 3D UVBF. In Specific Aim 2, serial ultrasound scans will develop prescriptive 3D UVBF reference standards in 400 non-anomalous fetuses with normal growth outcomes. In Specific Aim 3, circulatory patterns of multi-vessel Doppler velocimetry and 3D UVBF changes will be determined in a prospective cohort of 1100 small fetuses. The added value of 3D UVBF and related Doppler circulatory patterns in identifying small fetuses with adverse perinatal outcomes or neonatal morbidities will be examined. Successful execution of our Aims should establish 3D UVBF as a reproducible circulatory parameter that is accurate and clinically applicable as early as the first trimester. Our approach may improve detection and monitoring of small fetuses before conventional imaging predictors of adverse pregnancy outcomes become apparent.