Normal Fetal Umbilical, Portal, and Hepatic Venous System: Four-dimensional STIC Rendering.

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Independent validation of metric optimized gating for fetal cardiovascular phase-contrast flow imaging.

PURPOSE: To validate metric optimized gating phase-contrast MR (MOG PC-MR) flow measurements for a range of fetal flow velocities in phantom experiments. 2) To investigate intra- and interobserver variability for fetal flow measurements at an imaging center other than the original site. METHODS: MOG PC-MR was compared to timer/beaker measurements in a pulsatile flow phantom using a heart rate (∼145 bpm), nozzle diameter (∼6 mm), and flow range (∼130-700 mL/min) similar to fetal imaging. Fifteen healthy fetuses were included for intra- and interobserver variability in the fetal descending aorta and umbilical vein. RESULTS: Phantom MOG PC-MR flow bias and variability was 2% ± 23%. Accuracy of MOG PC-MR was degraded for flow profiles with low velocity-to-noise ratio. Intra- and interobserver coefficients of variation were 6% and 19%, respectively, for fetal descending aorta; and 10% and 17%, respectively, for the umbilical vein. CONCLUSION: Phantom validation showed good agreement between MOG and conventionally gated PC-MR, except for cases with low velocity-to-noise ratio, which resulted in MOG misgating and underestimated peak velocities and warranted optimization of sequence parameters to individual fetal vessels. Inter- and intraobserver variability for fetal MOG PC-MR imaging were comparable to previously reported values.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Large fetal intra-abdominal umbilical vein varix: Antenatal sonographic diagnosis and follow-up.

Fetal intra-abdominal umbilical vein varix is an uncommon antenatal finding defined as focal dilatation of umbilical vein >9 mm or more than two standard deviations above the mean for the gestational age. We report the case of a 28-year-old gravida 2 diabetic lady, who presented at 35 weeks of gestation, whose antenatal ultrasonography showed a cystic lesion of size 4 × 3.8 cm showing turbulent venous flow in the fetal abdomen in continuity with the umbilical vein, diagnosed as umbilical vein varix without any other anomaly. Postnatal ultrasonography showed size reduction and thrombosis of varix. Isolated umbilical vein varix has a favorable outcome, whereas those associated with other structural anomalies have a variable prognosis. This case was reported because of the unusually large size of varix with a good outcome and also to stress the importance of detailed sonography and close fetal monitoring in the presence of umbilical vein varix.

Type 1 and 3 inositol trisphosphate receptors are required for extra-embryonic vascular development.

The embryonic-maternal interface of the placental labyrinth, allantois, and yolk sac are vital during embryogenesis; however, the precise mechanism underlying the vascularization of these structures remains unknown. Herein we focus on the role of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), which are intracellular Ca(2+) release channels, in placentation. Double knockout (DKO) of type 1 and 3 IP3Rs (IP3R1 and IP3R3, respectively) in mice resulted in embryonic lethality around embryonic day (E) 11.5. Because IP3R1 and IP3R3 were co-expressed in endothelial cells in the labyrinth, allantois, and yolk sac, we investigated extra-embryonic vascular development in IP3R1- and IP3R3-DKO mice. The formation of chorionic plates and yolk sac vessels seemed dysregulated around the timing of the chorio-allantoic attachment, immediately followed by the disorganization of allantoic vessels, the decreased expression of the spongiotrophoblast cell marker Tpbpa and the growth retardation of the embryos in DKO mice. Fluorescent immunohistochemistry demonstrated downregulation of a vascular endothelial marker, CD31, in labyrinth embryonic vessels and poor elongation of extra-embryonic mesoderm into the labyrinth layer in DKO placenta, whereas the branching of the DKO chorionic trophoblast was initiated. In addition, allantoic and yolk sac vessels in extra-embryonic tissues were less remodeled in DKO mice. In vitro endothelial cord formation and migration activities of cultured vascular endothelial cells derived from human umbilical vein were downregulated under the inhibition of IP3R. Our results suggest that IP3R1 and IP3R3 are required for extra-embryonic vascularization in the placenta, allantois, and yolk sac. This is the first demonstration of the essential role of IP3/IP3Rs signaling in the development of the vasculature at the embryonic-maternal interface.

The fate of the vitelline and umbilical veins during the development of the human liver.

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo.

Sexual Dimorphism in Umbilical Vein Blood Flow During the Second Half of Pregnancy: A Longitudinal Study.

OBJECTIVES: To investigate gestational age-specific serial changes in umbilical vein (UV) volume blood flow during the second half of normal pregnancy and establish sex-specific reference ranges. METHODS: This work was a prospective longitudinal study of singleton low-risk pregnancies. The UV diameter and maximum blood flow velocity were serially measured by sonography at the intra-abdominal portion of the UV over 19 to 41 weeks. Umbilical vein volume blood flow was calculated and normalized for estimated fetal weight. RESULTS: One hundred seventy-nine women and their fetuses (87 male and 92 female) were included in the final analysis, and a total of 746 observations were used to construct sex-specific reference intervals. We found no statistically significant sex-specific differences in the UV parameters examined. However, the temporal development patterns of normalized UV volume blood flow appeared to differ between male and female fetuses during the second half of pregnancy, with crossovers at 24 and 32 weeks' gestation. CONCLUSIONS: Umbilical vein volume blood flow is similar among male and female fetuses in quantitative terms, but the pattern of gestational age-dependent temporal changes may be different, which may have important physiologic implications with regard to in utero development and maturation of the fetoplacental unit.

Hemodynamic studies of isolated absent ductus venosus.

OBJECTIVE: The objective of this article is to evaluate hemodynamic changes among fetuses with isolated absent ductus venosus (IADV) diagnosed by prenatal ultrasonography. PATIENTS AND METHODS: Fetuses with prenatal diagnosis of IADV were recruited and followed. Hemodynamic assessment was performed in all cases, including measurement of cardiac dimensions, shortening fraction, myocardial performance index, preload index in the inferior vena cava and the presence of venous pulsations in the umbilical vein (UV). RESULTS: Nine fetuses of IADV were assessed, including six cases with extra-hepatic UV drainage and three with intra-hepatic drainage. All fetuses with extra-hepatic UV drainage showed an elevated preload index in the inferior vena cava, venous pulsations in the UV and cardiomegaly. Of them, four had hydrops, two showed poor cardiac function and three resulted in perinatal mortality. Three cases with intra-hepatic drainage had continuous flow in the UV, normal in all hemodynamic parameters and all survived. CONCLUSION: Hemodynamic assessment of fetuses with IADV was helpful in predicting the development of hydrops and perinatal mortality. The poor prognostic factors included cardiac overload, cardiomegaly, poor myocardial performance, increased preload, the presence of venous pulsations and extra-hepatic UV drainage. © 2015 John Wiley & Sons, Ltd.

A retrospective single centre review of the incidence and prognostic significance of persistent foetal right umbilical vein.

The objective of our study was to appraise the incidence and significance of persistent right umbilical vein (PRUV), the most common foetal venous aberration. Based on a south Indian antenatal cohort, we identified 23 cases of PRUV amongst 20,452 foetuses of consecutive pregnancies, from 2009 to 2014, yielding an incidence of 1 in 889 total births (0.11%). The median maternal age was 24 (IQR, 22-26) years, and median gestational age at diagnosis was 23 (IQR, 22-24) weeks. Intrahepatic drainage of PRUV was seen in 91.3% cases. In three cases (13%), ductus venosus was absent. In 52.2% of the cases, additional major abnormalities were observed - predominantly cardiovascular (39.1%). The common minor marker was single umbilical artery (13%). The karyotype was found to be normal in six cases (26%) which underwent invasive testing. When associated anomalies were inconsequential or absent, the postnatal outcome was good, which reflected in 60.9% of our cases.

Systematic examination of the fetal abdominal precordial veins: a cohort study.

OBJECTIVES: Examination of the fetal venous system is a necessary part of complete fetal organ scanning to confirm landmark anatomy, such as the ductus venosus and course of the umbilical veins, and, whenever cardiovascular anomalies are identified, to exclude associated anomalous development of the fetal veins. We aimed to develop a protocol for systematic examination of the fetal venous system during midtrimester targeted organ scanning. METHODS: We included low-risk women with a singleton fetus presenting between January 2011 and June 2013 to our center for routine midtrimester (20-24 weeks) targeted organ scanning. Imaging of the venous system was added to the booked scan and comprised two-dimensional color Doppler scanning of the fetal abdomen in three discrete planes, two transverse and one longitudinal. The more caudal plane was obtained in a ventral or lateral transverse abdominal plane to image the umbilical vein, left portal vein, portal sinus, anterior right portal vein, posterior right portal vein, main portal vein and splenic vein and artery. Moving cephalad, a ventral or lateral transverse plane was obtained to image the right, middle and left hepatic veins and inferior vena cava (IVC). Finally, a longitudinal anteroposterior plane showed the umbilical vein, ductus venosus, IVC and left hepatic vein. In some cases the pulsed Doppler waveform of a given target vessel was also examined. Three-dimensional/4D ultrasound was applied as necessary, when anomalous cases were encountered. RESULTS: We examined 1810 women. Their body mass index ranged from 19 to 40 (mean, 24.7). In 38 (2.1%) women, the target anatomy was not visualized satisfactorily owing to maternal body habitus. A T-shaped configuration of the portal system vessels was observed in 63% of cases, an X-shaped configuration in 25% and an H-shaped configuration in 12%. During the study period, 24 congenital anomalies of the precordial venous system were diagnosed: nine cases of persistent right umbilical vein, seven of agenesis of the ductus venosus, five of anomalous portal venous drainage and three of interrupted IVC with azygos continuation. CONCLUSIONS: Examination of the fetal venous system is feasible with the application of three abdominal planes. While a venous system scan is not practicable as part of a screening-level examination, mastery of the normal anatomy is an essential part of the professional knowledge base, in order to provide ready and complete scanning of the system in cases of suspected anomalies or disordered cardiac function.

Time-interval analysis of ductus venosus flow velocity waveforms in twin-to-twin transfusion syndrome treated with laser surgery.

OBJECTIVES: To investigate time-interval variables of ductus venosus (DV) flow velocity waveforms (FVWs) in twin-to-twin transfusion syndrome (TTTS), comparing the results with reference ranges from normal singleton fetuses. The impact of laser surgery and the effect of prognostic factors were also evaluated. METHODS: In 107 TTTS cases, DV-FVWs of both recipients and donors were recorded 1 day before and 2 days after laser therapy. Time intervals for systolic (S) and early diastolic (D) peaks were analyzed retrospectively with regard to acceleration time (acc-S and acc-D for S and D, respectively) and deceleration time (dec-S and dec-D for S and D, respectively). For each variable, Z-scores were calculated with respect to previously reported normal reference ranges. RESULTS: Z-scores for all variables showed statistically significant differences from those observed previously in normal fetuses, with the exception of dec-S of donors. The most striking differences were observed in longer dec-S of recipients (P < 0.001) and longer dec-D of donors (P < 0.001). Laser therapy showed significant impact on dec-S and acc-D in recipients and on all variables in donors. Regarding the short-term prognosis, acc-S and dec-S showed significant differences for the prediction of intrauterine fetal demise in donors (P = 0.009 and P = 0.011, respectively). CONCLUSION: This study demonstrates that time-interval variables of DV-FVWs may differentiate the characteristic hemodynamic changes caused by unbalanced blood volume between recipients and donors.

Reference ranges for ductus venosus velocity ratios in pregnancies with normal outcomes.

OBJECTIVES: The purpose of this study was to establish reference ranges for ductus venosus velocity ratios. METHODS: Singleton pregnancies from 11 to 38 weeks with exactly established gestational ages (GAs) were recruited for the study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical complications, stillbirth, birth weight below the 10th or above the 90th percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a, where S indicates ventricular systole [s-wave], v, ventricular end-systolic relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a, active ventricular filling during atrial systole [a-wave]) were calculated. Separate regression models were fitted to estimate the mean and standard deviation at each GA for each ratio. RESULTS: A total of 902 velocity wave ratios and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a ratios were reduced with GA (P < .0001 for all). Significant reductions in the means and standard deviations of the PIV and S/a, v/a, and D/a ratios were observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately created between 11 and 17 weeks and 18 and 38 weeks. CONCLUSIONS: We created reference ranges for ductus venosus velocity ratios between 11 and 38 weeks' gestation in normal pregnancies. These reference ranges may prove beneficial for evaluation of fetal conditions that are associated with cardiovascular abnormalities.

A reference for ductus venosus blood flow at 11-13+6 weeks of gestation.

OBJECTIVE: To establish reference ranges for ductus venosus (DV) blood flow assessment obtained transabdominally at 11-13(+6) weeks of gestation. METHODS: A cross-sectional study was conducted on singleton pregnancies with a crown-rump length (CRL) ranging from 45 to 84 mm, normal fetus, and subsequent newborn birth weight appropriate for gestational age. Measurements of DV Doppler variables were performed by experienced sonographers: peak velocity during ventricular systole (S-wave) and diastole (D-wave), nadir during atrial contraction (A-wave), time-averaged maximum velocity (TAmax), pulsatility index for veins (PIV), and peak velocity index for veins (PVIV). RESULTS: A total of 304 fetuses were included. The mean CRL was 60.7 ± 7.2 mm (range: 45.9-75.5). The mean nuchal translucency measurement was 1.4 ± 0.4 mm. The S-wave, D-wave, A-wave, and TAmax values varied significantly with gestational age (p < 0.05) and regression models were constructed for each variable. The remaining variables, systolic/atrial wave ratio, preload index, PVIV, and PIV, did not vary significantly with gestational age within this CRL range. CONCLUSION: Reference ranges for DV Doppler assessment were established in normal fetuses. These ranges may be a useful tool for evaluation of anueploidy and fetal cardiac function.

Ultrasound of the fetal veins part 1: the intrahepatic venous system.

Advances in high-resolution ultrasound combined with color Doppler and three-dimensional (3 D) rendering have contributed to an increasing understanding of the fetal venous circulation in recent years. Still the sonographic evaluation of the venous system in the fetus remains difficult. This article reviews the normal and abnormal intrahepatic venous system. Normal anatomy and abnormal findings of the umbilical vein (UV), the ductus venosus (DV), portal veins, hepatic veins and the inferior vena cava are demonstrated by grayscale, color Doppler and 3D ultrasound and explained by numerous schemes. Typical variants and abnormalities such as agenesis of the DV and portal venous system, persistence of the right UV, UV varix are explained and the clinical value of normal and abnormal Doppler findings in the DV is discussed. Many of these abnormal findings can be detected by a targeted examination of the intrahepatic vasculature with means of color Doppler.

Retrograde diastolic blood flow in the aortic isthmus is not a simple marker of abnormal fetal outcome in pregnancy complicated by IUGR--a pilot study.

AIM: To evaluate the relation between retrograde diastolic blood flow in the aortic isthmus and adverse perinatal outcome in fetuses with IUGR. MATERIALS AND METHODS: The study included 33 fetuses with IUGR defined as the estimated fetal weight and abdominal circumference under the 10th percentile for a given gestational age. The Doppler examination of the blood flow in the aortic isthmus, umbilical artery umbilical vein, middle cerebral artery uterine arteries and ductus venosus was performed regularly The study population was further divided into two subgroups, depending on the aortic isthmus blood flow direction, i.e. with and without retrograde isthmic diastolic flow. Furthermore, the relation between Doppler blood flow parameters and determinants of the perinatal outcome was analyzed. The perinatal outcome was reported as adverse if any of the following occurred: umbilical cord blood pH < 7,2; 5-minute Apgar score < 7; respiratory distress syndrome, intraventricular hemorrhage (/ll/IV grade); necrotizing enterocolitis; sepsis; intrauterine or neonatal death. RESULTS: There was no statistically significant difference in the incidence of adverse perinatal outcome between the antegrade and retrograde isthmic blood flow groups. Moreover; the study showed no statistically significant relationship between the retrograde blood flow in the aortic isthmus and the prevalence of abnormal flow in the analyzed vessels. CONCLUSION: Retrograde diastolic blood flow in the aortic isthmus presents a low sensitivity and low predictive value in predicting the adverse perinatal outcome in pregnancies complicated with IUGR.

Fetal umbilical vein deviation in congenital diaphragmatic hernia.

OBJECTIVES: Deviation of the intra-abdominal umbilical vein has been described as a marker of congenital diaphragmatic hernia (CDH) and has been shown to help identify liver herniation into the fetal chest. The purpose of this study was to quantify the degree of deviation in affected fetuses and to determine the accuracy of measurements for diagnosing liver herniation. METHODS: In patients undergoing prenatal sonography for CDH, the midhepatic portion of the umbilical vein was identified, and the distance between the lateral edge of the vein and the inner rib margin was measured. The same was done on the right, and the ratio of the left to right measurement was termed the "umbilical vein ratio." The accuracy of the umbilical vein ratio for predicting the presence and side of the hernia and for diagnosing liver herniation was determined. RESULTS: All but 1 of the cases with right-sided hernias had an umbilical vein ratio above the normal range, and all had liver herniation. Of those with a left-sided hernia, only 2 had a ratio within the normal range. Of those with a left-sided hernia, an umbilical vein ratio less than 0.4 was shown by receiver operating characteristic curve analysis to be the best predictor of liver herniation. This cutoff had sensitivity of 89% for predicting herniation, with a false-positive rate of 14%. CONCLUSIONS: Ninety-three percent of right-sided CDH lesions and 98% of left-sided lesions have an umbilical vein ratio outside the normal range. This finding shows that deviation may a useful indicator of CDH in screening ultrasound examinations. An umbilical vein ratio less than 0.4 is predictive of liver herniation.

Two- and three-dimensional sonographic diagnosis of fetal intra-abdominal umbilical vein varix: a case report.

Fetal intra-abdominal umbilical vein varix is a rare condition characterized by focal dilatation of the umbilical vein of the fetus. We report a case of fetal intra-abdominal umbilical vein varix associated with additional sonographic abnormalities and detected at 31 weeks' gestation. Several follow-up sonographic examinations were performed, and the prenatal findings were confirmed on postnatal ultrasound. The diagnosis was facilitated by the use of three-dimensional power Doppler sonography.

Missing ductus venosus: a case report.

BACKGROUND: The ductus venosus is a short vessel, present in the newborn infant on the dorsal surface of the liver, connecting the portal and umbilical circulation with the inferior vena cava. Agenesis of the duct is a rare anomaly. CASE: A 28-year-old woman was referred to our department for the first trimester ultrasound evaluation. Detailed scanning revealed agenesis of the duct. Fetal echocardiography showed cardiac disproportion at the level of the ventricles. CONCLUSION: Agenesis of the duct can be related to either cardiac or congenital abnormalities.