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的独立预测因子， 非异常胎儿的死亡率。然而，单独的胎儿生物测量不能可靠地区分小 那些体质小的胎儿有不良结局的风险。了相当大的努力 旨在开发更可靠的方法，用于检测和监测有风险的小胎儿， 不良后果。测量脐静脉血流量（UVBF）的常规努力，使用常规的 使用多普勒测速仪进行2D血管直径测量具有挑战性，因为技术因素 使其对于常规临床实践不切实际。我们将通过使用3D超声测量来解决这个问题。 脐静脉血流量（3D UVBF）。该方法将彩色血流多普勒超声与2D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量化体积流量， 多普勒超声角度、流速剖面或血管几何形状。假设：1）3D UVBF是一个准确的， 测量整个妊娠期脐静脉血流的可重复超声参数; 2）参考 3D UVBF标准将很容易生成，为前瞻性分析提供必要的框架; 和3）基于3D UVBF的可预测的和进行性的循环恶化模式显著发生 与其他小胎儿相比，小胎儿（EFW < 10th%）更常见不良结局 胎儿无并发症。初步数据：我们已经表明，3D UVBF %误差，相对于平均值 在妊娠母羊的外置胎儿中，9次测量中有8次测量的动脉和静脉血流≤ 10%。 低于预期的3D UVBF值被发现在2/7的胎儿从人类怀孕，后来开发 FGR或先兆子痫（Pinter S等人，J Ultrasound Med 37：1633-1640，2018）。在进一步的再现性研究中， 3D UVBF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 %（平均值± SD）（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EFW <10 th %的小胎儿循环变化的详细观察结果。 在特定目标1中，将检查孕妇的体外流动体模实验和再现性研究 3D UVBF的准确性和再现性。在《特定目标2》中，连续超声扫描将开发出处方性 400例正常生长结局的非异常胎儿的3D UVBF参考标准。在具体目标3中， 多血管多普勒流速仪的循环模式和3D UVBF变化将在一个 1100例小胎儿的前瞻性队列研究。3D UVBF和相关多普勒循环模式的附加值 在识别小胎儿不良围产期结局或新生儿发病率将进行检查。成功 我们的目标的执行应将3D UVBF确立为可重现的循环参数， 早在妊娠前三个月就可应用于临床。我们的方法可以改善小的检测和监测 在常规影像学检查之前，不良妊娠结局的预测因素变得明显。

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.