Impact of choroid plexus size in prenatal diagnosis of normal and abnormal closure of fourth ventricle.

OBJECTIVE: To assess the role of the choroid plexus (CP) of the fourth ventricle (4V) in fetuses with an open 4V and a normal cerebellar vermis. METHODS: Two groups of patients were recruited in two fetal medicine referral centers. The prospectively collected control group included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome, recruited in the period between 2019 and 2022. The study group was selected retrospectively by searching our databases to identify all cases with an isolated open 4V and normal anatomy and size of the cerebellar vermis. The inclusion criteria of the study group were: (1) gestational age between 20 and 22 weeks; (2) a brainstem-vermis angle ≥ 18° in the midsagittal plane with an otherwise normal cerebellum and vermis; (3) 4V-CP visible and seen separately from the vermis; (4) absence of other intra- and extracranial anomalies; and (5) available prenatal and/or postnatal magnetic resonance imaging (MRI) data. RESULTS: In 169 cases of the control group, the 4V-CP was seen separately from the cerebellar vermis and was noticed to progressively fill the space caudal to the 4V, between the vermis and brainstem. From 12 to 22 weeks, the surface areas of the vermis and medial portion of the 4V-CP increased progressively with advancing gestation (P < 0.0001). Intra- and interobserver correlation analysis showed good reproducibility for the measurements. Among the cases with an open 4V and a normal vermis, it was retrospectively feasible to visualize the 4V-CP separately from the inferior part of the vermis in 41 fetuses. In five of these cases, the open 4V was due to a small CP. In all 41 fetuses, the diagnosis on MRI was isolated upward rotation of the cerebellar vermis, and no additional anomaly was found. CONCLUSIONS: Closure of the 4V is dependent on the 4V-CP and not only the cerebellar vermis. In fact, a small CP may represent another cause of an open 4V. Therefore, separate visualization of the 4V-CP and cerebellar vermis is crucial to improve discrimination between the different causes of an open 4V at the anomaly scan and its clinical implications. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Low torcular Herophili position and large brainstem-tentorium angle in fetuses with open spinal dysraphism at 11-13 weeks' gestation.

OBJECTIVE: To evaluate whether in fetuses with open spina bifida (OSB) the tentorium can be seen to be displaced downwards and vertically oriented by the time of the 11-13-week scan and whether this is reflected in an alteration of the brainstem-tentorium (BST) angle. METHODS: The study population was recruited between 2015 and 2020 from three fetal medicine referral centers and comprised a control group and a study group of pregnancies with OSB. The control group was recruited prospectively and included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome. The study group was selected retrospectively and included all cases with OSB between 2015 and 2020. All cases underwent detailed ultrasound assessment at 11 + 0 to 13 + 6 weeks' gestation. The position of the torcular Herophili (TH) was identified in the midsagittal view of the fetal brain with the use of color Doppler and was considered as a proxy for the insertion of the tentorium on the fetal skull. The BST angle was calculated in the same view and was compared between the two groups. RESULTS: Sixty normal fetuses were included in the control group and 22 fetuses with OSB in the study group. In both groups, the BST angle was found to be independent of gestational age or crown-rump length (P = 0.8815, R2 = 0.0003861 in the controls, and P = 0.2665, R2 = 0.00978 in the OSB group). The mean BST angle was 48.7 ± 7.8° in controls and 88.1 ± 1.18°, i.e. close to 90°, in fetuses with OSB. Comparison of BST-angle measurements between the control group and cases with OSB showed a statistically significant difference (P = 0.0153). In all fetuses with OSB, the downward displacement of the TH and tentorium was clearly visible at the 11-13-week scan. CONCLUSIONS: In fetuses with OSB, the BST angle is significantly larger than in normal controls, with the tentorium being almost perpendicular to the brainstem. This sign confirms the inferior displacement of the tentorium cerebelli with respect to its normal insertion on the occipital clivus as early as the first trimester of pregnancy and is useful in the diagnosis of Chiari-II malformation at this early stage. In fetuses with OSB, the low position of the tentorium and TH is clearly visible, even subjectively, at the 11-13-week scan. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Position of the choroid plexus of the fourth ventricle in first- and second-trimester fetuses: a novel approach to early diagnosis of cystic posterior fossa anomalies.

OBJECTIVE: To describe the sonographic appearance and position of the choroid plexus of the fourth ventricle (4V-CP) between 12 and 21 weeks' gestation in normal fetuses and in fetuses with Dandy-Walker malformation (DWM) or Blake's pouch cyst (BPC). METHODS: The study population comprised 90 prospectively recruited normal singleton pregnancies and 41 pregnancies identified retrospectively from our institutional database that had a suspected posterior fossa anomaly at 12-13 weeks' gestation based on the ultrasound finding of abnormal hindbrain spaces. In all cases the final diagnosis was confirmed by prenatal and/or postnatal magnetic resonance imaging or postmortem examination. All pregnancies underwent a detailed ultrasound assessment, including a dedicated examination of the posterior fossa, at 12-13 weeks, 15-16 weeks and 20-21 weeks of gestation. Two-dimensional ultrasound images of the midsagittal and coronal views of the brain through the posterior fontanelle and three-dimensional volume datasets were obtained. Multiplanar orthogonal image correlation with volume contrast imaging was used as the reference visualization mode. Two independent operators, blinded to the fetal outcome, were asked to classify the 4V-CP as visible or not visible in both normal and abnormal cases, and to assess if the 4V-CP was positioned inside or outside the cyst in fetuses with DWM and BPC. RESULTS: Of the 41 fetuses with apparently isolated cystic posterior fossa anomaly in the first trimester, eight were diagnosed with DWM, 29 were diagnosed with BPC and four were found to be normal in the second trimester. The position of the 4V-CP differed between DWM, BPC and normal cases in the first- and second-trimester ultrasound examinations. In particular, in normal fetuses, no cyst was present and, in the midsagittal and coronal planes of the posterior fossa, the 4V-CP appeared as an echogenic oval-shaped structure located inside the 4V apparently attached to the cerebellar vermis. In fetuses with DWM, the 4V-CP was not visible in the midsagittal view because it was displaced inferolaterally by the cyst. In contrast, in the coronal view of the posterior brain, the 4V-CP was visualized in all cases with DWM at 12-13 weeks, with a moderate decrease in the visualization rate at 15-16 weeks (87.5%) and at 20-21 weeks (75%). In the coronal view, the 4V-CP was classified as being outside the cyst in all DWM cases at 12-13 weeks and in 87.5% and 75% of cases at 15-16 and 20-21 weeks, respectively. In fetuses with BPC, the 4V-CP was visualized in all cases in both the midsagittal and coronal views at 12-13 weeks and in 100% and 96.6% of cases, respectively, at 15-16 weeks. In the coronal view, the 4V-CP was classified as being inside the cyst in 28 (96.6%), 27 (93.1%) and 25 (86.2%) cases at 12-13, 15-16 and 20-21 weeks, respectively. The medial segment of the 4V-CP was visualized near the inferior part of the vermis. CONCLUSIONS: Our study shows that longitudinal ultrasound assessment of the 4V-CP and its temporal changes from 12 to 21 weeks is feasible. The 4V-CP is located inside the cyst, just below the vermis, in BPC and outside the cyst, inferolaterally displaced and distant from the vermian margin, in DWM, consistent with the pathogenesis of the two conditions. The position of the 4V-CP is a useful sonographic marker that can help differentiate between DWM and BPC as early as in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal Brain MR Imaging: Reference Linear Biometric Centiles between 20 and 24 Gestational Weeks.

BACKGROUND AND PURPOSE: Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. MATERIALS AND METHODS: From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. RESULTS: Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. CONCLUSIONS: Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development.

Sphenofrontal distance on three-dimensional ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation.

OBJECTIVE: To compare the distance between the sphenoid and frontal bones on three-dimensional (3D) ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation. METHODS: We acquired 3D volumes of the fetal profile from 80 normal and 30 trisomy-21 fetuses at 16-24 weeks' gestation. We used the multiplanar mode to obtain the mid-sagittal plane and measured the sphenofrontal distance as the shortest distance between the most anterior edge of the sphenoid bone and the lowest edge of the frontal bone. RESULTS: In normal fetuses, the sphenofrontal distance increased linearly with gestational age, from 15.1 mm at 16 weeks to 18.2 mm at 24 weeks. In fetuses with trisomy 21, the mean sphenofrontal distance delta value was significantly smaller than in normal cases (-3.447 mm (95% CI, -5.684 to -1.211 mm); P < 0.01). The sphenofrontal distance was below the 5(th) and 1(st) percentiles of the normal range in 29 (96.7%) and 27 (90.0%) trisomy-21 fetuses, respectively. CONCLUSIONS: The sphenofrontal distance is shorter at 16-24 weeks' gestation in fetuses with trisomy 21 than in normal fetuses. A reduction in the growth of the anterior cranial base contributes to the mid-facial hypoplasia observed in fetuses with trisomy 21. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Uterine artery blood flow volume in pregnant women with an abnormal pulsatility index of the uterine arteries delivering normal or intrauterine growth restricted newborns.

The aim of this study was to assess and compare uterine artery (UtA) blood flow volume in pregnant patients with an abnormal uterine Doppler pulsatility index (PI) who delivered fetuses with an appropriate weight for gestational age (AGA) or with intrauterine growth restricted (IUGR). We prospectively recruited singleton pregnancies with abnormal uterine arteries P.I. between 18 and 38 weeks of gestation regardless of estimated fetal weight (EFW). Vessel diameter and blood flow velocity were measured along the UtA upstream to the vessel bifurcation in both the right and left UtAs. Uterine blood flow volumes measured in these pregnancies were compared to historical Control-pregnancies. Forty-three patients delivered at term a normal weight newborn (AGA-pregnancies). Thirty patients delivered growth restricted newborns at 32 weeks (i.r. 29-36w) with a median weight of 1160 gr (i.r. 1000-2065 gr) (IUGR-pregnancies). At mid-gestation (18 + 0 - 25 + 6 weeks + days of gestation) a significantly lower uterine blood flow volume per unit weight was observed between the two study groups and compared to controls: 142 ml/min/kg in IUGR-pregnancies, 217 ml/min/kg in AGA-pregnancies and 538 ml/min/kg in Control-pregnancies. These striking differences in blood flow volume were already present at mid-gestation, at a time when EFW was still normal. In late gestation (27 + 0 - 37 + 6 weeks + days of gestation), pregnancies with an abnormal uterine P.I. showed persistently low UtA flow (<50% of controls) even when corrected for fetal weight: 81 ml/min/kg in IUGR-pregnancies, 105 ml/min/kg in AGA-pregnancies, and 193 ml/min/kg in Control-pregnancies; p < 0.0001. Our findings are consistent with other recent studies regarding the association between reduced uterine blood flow volume and fetal growth restriction. However, the study brings new insight into the finding of abnormal uterine P.I. in normally grown fetuses typically dismissed as "falsely abnormal" or "false positive" findings. Our study suggests that blood flow volume measurement may serve as a new tool to assess this group of patients and possibly those with ischemic placental diseases that may provide some basis for therapeutic interventions.

Blood flow volume of uterine arteries in human pregnancies determined using 3D and bi-dimensional imaging, angio-Doppler, and fluid-dynamic modeling.

The primary aim of this pilot study was to study uterine artery (UtA) blood flow volume in uneventful human pregnancies delivered at term, at mid and late gestation by means of 3D and bi-dimensional ultrasound imaging with angio-Doppler combined with fluid-dynamic modeling. Secondary aims were to correlate flow volume to placental site and to UtA Pulsatility Index (PI). Women with singleton, low-risk pregnancies were examined at mid and late gestation. The structure and course of the uterine artery (UtA) was studied in each patient by means of 3D-angio-Doppler and included vessel diameter D, blood flow velocity and PI (measured along the UtA). Fetal weight estimation and placental insertion site were assessed by ultrasound. A robust fluid-dynamic modeling was applied to calculate absolute flow and flow per unit fetal weight. Mean UtA diameter and blood flow velocity increased significantly (p < 0.0001) from mid-gestation to late gestation from 2.6 mm and 67.5 cm/s, to 3.0 mm and 85.3 cm/s, respectively, yielding an increasing absolute flow troughout gestation. h coefficient, derived by fluid-dynamic modeling to calculate mean velocity, increased significantly from 0.52 at mid-gestation to 0.57 at late gestation. UtA blood flow volume ml/min/kg-fetal weight was significantly higher at mid-gestation than at late gestation (535 ml/min/kg vs 193 ml/min/kg; p < 0.0001). In cases with strictly lateral placentas the ipsilateral UtA accommodates at mid and late gestation 63% and 67% of the total UtA flow. In central placentas UtA flow was evenly distributed between the two vessels. An inverse correlation was observed between PI and blood flow volume ml/min/kg (Pearson's coefficient r = -0.54). Our work confirms the technological and methodological limitations in the measurement of uterine artery blood flow. However, Doppler measurements supported by three-dimensional angio imaging of the uterine vessel, high resolution imaging and diameter measurement, and a robust mathematical model of local circulation adds a genuine new area of investigation into human uterine circulation during pregnancy.

The impact of maternal plasma volume expansion and antihypertensive treatment with intravenous dihydralazine on fetal and maternal hemodynamics during pre-eclampsia: a clinical, echo-Doppler and viscometric study.

OBJECTIVES: To establish the effects of plasma volume expansion (PVE) followed by intravenous dihydralazine (DH) administration on maternal whole blood viscosity (WBV) and hematocrit, uteroplacental and fetoplacental downstream impedance and umbilical venous (UV) volume flow in pre-eclampsia. METHODS: In 13 pre-eclamptic women maternal and fetal hemodynamics were established by means of combined measurement of maternal arterial blood pressure (BP), WBV, hematocrit and uterine artery (UtA) resistance index (RI) in addition to umbilical artery (UA) pulsatility index (PI) and UV volume flow obtained from UV vessel area and UV time-averaged flow velocity. In each woman all parameters were measured four times at baseline, after PVE, after DH and 24 h after the start of treatment. RESULTS: Maternal diastolic BP, hematocrit and WBV display a significant reduction after PVE. In the fetus UA PI decreases significantly whereas a significant increase in UV cross-sectional area was detected. After maternal DH administration, arterial systolic and diastolic BP and UA PI show a significant decrease compared with the measurements following PVE. At 24 h, only maternal systolic and diastolic BP display a significant further decrease. No significant changes were established for the UtA RI, UV time-averaged velocity and UV volume flow during the entire study period. CONCLUSIONS: During pre-eclampsia, maternal PVE followed by DH administration results in a significant reduction in maternal diastolic BP, maternal hematocrit and WBV. Maternal PVE is associated with a significant increase in UV cross-sectional area and a non-significant rise of 11% in UV volume flow. Maternal DH administration does not result in any change in UV cross-sectional area. However, UA PI decreases significantly after both PVE and DH treatment.

Umbilical venous volume flow and fetal behavioral states in the normally developing fetus.

OBJECTIVE: To determine the relationship between umbilical venous (UV) volume flow and fetal behavioral states 1F (quiet sleep) and 2F (active sleep) in normal pregnancies at 36-40 weeks of gestation. METHODS: Fetal behavioral states were established in 17 normal pregnancies by means of combined assessment of fetal heart rate patterns (FHRP), and fetal eye and body movements. UV vessel area (mm(2)) as obtained by tracing the inner vessel area using Labview and Imaq Vision software and UV time-averaged flow velocity (mm/s Doppler) were multiplied to calculate UV volume flow (mL/min) including flow/kg fetus. The pulsatility index (PI) in the umbilical artery was also determined. In each woman, all parameters were measured between three and five times in each behavioral state. Data are reported as mean +/- 1 SD and analyzed by paired t-test. RESULTS: No statistically significant behavioral-state-related changes were observed for UV time-averaged velocity and UV volume flow, resulting in UV volume flow/kg fetus of 69.1 +/- 14.9 mL/min*kg at 1F and 71.6 +/- 12.1 mL/min*kg at 2F (not significant). A statistically significant increase (P = 0.02) was established for UV cross-sectional area (46.4 +/- 8.6 mm(2) vs. 49.0 +/- 10.1 mm(2)) and for fetal heart rate (FHR) from 134.2 +/- 10.3 bpm in 1F to 144.2 +/- 7 bpm in 2F. Umbilical artery PI was not significantly different between the two behavioral states. CONCLUSIONS: On the basis of high venous vessel wall compliance, the significant increase in UV cross-sectional area during fetal behavioral state 2F may be determined by a rise in mean venous pressure. The significant rise in FHR may reflect increased fetal cardiac output during state 2F while the resistance at the hepato-ductal pathway remains relatively constant with the purpose of meeting raised energy demands during the active sleep state. This is further supported by the observed trend towards an increase in UV volume flow.

Fetal brain/liver volume ratio and umbilical volume flow parameters relative to normal and abnormal human development.

OBJECTIVES: To estimate fetal brain volume from head circumference and published postmortem data; to determine normal values for the fetal brain/liver volume ratio relative to gestational age; to establish the relationship between the brain/liver volume ratio and fetal circulatory parameters during normal and restricted (SGA) fetal growth. PATIENTS AND METHOD: This was a cross-sectional study involving a total of 47 uncomplicated pregnancies appropriate-for-gestational age (AGA) and 23 pregnancies resulting in the delivery of a SGA fetus. At enrollment gestational age ranged between 20 and 36 weeks in both groups. Umbilical venous cross-sectional area and time-averaged velocity for calculation of volume flow as well as velocity waveforms from the umbilical artery, middle cerebral artery and ductus venosus, were recorded. Fetal liver volume measurements were obtained using three-dimensional ultrasound. Fetal brain volume was estimated from fetal head volume following comparison with published postmortem data on fetal brain weight. RESULTS: A significant correlation was observed between prenatally estimated fetal head volume and postmortem fetal brain volume. Fetal brain volume was approximately half that of fetal head volume. The normal fetal brain/liver volume ratio demonstrated a significant reduction with gestational age (R = -0.54; P < 0.001). The normal mean +/- standard deviation (SD) fetal brain/liver volume ratio (3.4 +/- 0.7) was significantly different (P < 0.001) from the mean fetal brain/liver volume ratio in the SGA group (n = 23) (5.9 +/- 1.9). A significant difference existed for mean umbilical venous volume flow between AGA (104.7 +/- 26.9 mL/min/kg) and SGA (59.6 +/- 22.7 mL/min/kg) fetuses. In the SGA fetus, there was a significant inverse relationship (P < 0.001) between fetal weight-related umbilical venous volume flow and fetal brain/liver volume ratio. In a subset of 16 SGA and 16 AGA fetuses matched for gestational age, a significant difference existed for umbilical artery pulsatility index (2.30 +/- 1.52 vs. 0.99 +/- 0.19), fetal middle cerebral artery pulsatility index (1.3 +/- 0.4 vs. 2.1 +/- 0.3) and late diastolic flow velocity in the fetal ductus venosus (6.9 +/- 14.2 cm/s vs. 23.9 +/- 8.8 cm/s), but not for peak systolic, early diastolic and time-averaged velocity in the ductus venosus. CONCLUSION: Sonographic estimates of fetal brain volume can be obtained. The fetal brain/liver volume ratio is a predictor of fetal outcome in the growth-restricted fetus. An inverse relationship exists in SGA fetuses between brain/liver volume ratio and fetal weight-related umbilical venous blood flow.

Umbilical venous volume flow in the normally developing and growth-restricted human fetus.

OBJECTIVE: To determine the reproducibility of measurement of umbilical venous volume flow components and to calculate umbilical venous volume flow in normal and growth-restricted (small-for-gestational age) fetuses in a cross-sectional study. METHOD: Using Labview and Imaq-vision software, the cross-sectional inner area of the umbilical vein was traced. Vessel area (mm2) and Doppler-derived time-averaged flow velocity (mm/s) were multiplied to calculate volume flow (mL/min) including flow per kg fetal weight. The coefficient of variation for vessel area and flow velocity scans and tracings were determined (n = 13; 26-35 weeks). Normal charts for components and volume flow were constructed (n = 100; 20-36 weeks) and related to data from growth restricted fetuses (birth weight < 5th centile) (n = 33; 22-36 weeks). In growth-restricted fetuses the umbilical artery pulsatility index was also obtained. RESULTS: Reproducibility: The coefficient of variation was 5.4% (vessel area) and 7.3% (time-averaged velocity) for scans and 6.6% and 10.5% for measurements, resulting in a coefficient of variation of 8.1% (scans) and 11.9% (measurements) for volume flow. A gestational age-related increase exists for vessel area, time-averaged flow velocity and umbilical venous volume flow from 33.2 (SD, 15.2) mL/min at 20 weeks to 221.0 (SD, 32.8) mL/min at 36 weeks of gestation, but there is a reduction from 117.5 (SD, 33.6) mL/min to 78.3 (SD, 12.4) mL/min for volume flow per kg fetal weight. In small-for-gestational age fetuses, the values were below the normal range in 31 of 33 cases for volume flow and in 21 of 33 cases for volume flow per kg fetal weight. Umbilical artery pulsatility index was significantly different between the subsets with normal and those with reduced volume flow per kg fetal weight. CONCLUSIONS: Measurements of umbilical venous vessel area and time-averaged velocity resulted in acceptable reproducibility of volume flow calculations, which show a seven-fold increase at 20-36 weeks of gestation. In growth-restricted fetuses, volume flow is significantly reduced. When calculated per kg/fetus, the values were reduced in 21 (63.6%) out of 33 cases.