Fetal brain biometry and cortical development in congenital heart disease: A prospective cross sectional study.

OBJECTIVE: To evaluate brain biometry and cortical development by neurosonography in fetuses with congenital heart defect (CHD) and evaluate differences among different type of CHD. METHODS: In a prospective cross sectional study singleton fetus with CHD were matched with controls and grouped into two categories according to the predicted severity of cerebral arterial oxygen deficit induced by the CHD: Group A mildly reduced or normal and Group B moderately to severely reduced. Neurosonography was done at 30-33 weeks to obtain measurements of corpus callosum (CC), cerebellar vermis (CV), Sylvian fissure (SF) insula, parieto-occipital fissure (POF), and calcarine sulci fissures (CSF). All the neurosonographic parameters were adjusted by head circumference (HC). RESULTS: A total of 78 fetuses with CHD (group A 30; group B 48) and 80 matched controls form uncomplicated pregnancies were considered. CHD fetuses have significantly smaller CC, CV, SF, and POF and bigger insula when compared to control fetuses. These differences are more marked in group B fetuses. These differences remained significant after correction for HC values. CONCLUSION: Fetuses with CHD have an impaired cortical development and these variations are more evident in those with a predicted lower oxygen delivery to the brain.

5D CNS+ Software for Automatically Imaging Axial, Sagittal, and Coronal Planes of Normal and Abnormal Second-Trimester Fetal Brains.

The purpose of this study was to test new 5D CNS+ software (Samsung Medison Co, Ltd, Seoul, Korea), which is designed to image axial, sagittal, and coronal planes of the fetal brain from volumes obtained by 3-dimensional sonography. The study consisted of 2 different steps. First in a prospective study, 3-dimensional fetal brain volumes were acquired in 183 normal consecutive singleton pregnancies undergoing routine sonographic examinations at 18 to 24 weeks' gestation. The 5D CNS+ software was applied, and the percentage of adequate visualization of brain diagnostic planes was evaluated by 2 independent observers. In the second step, the software was also tested in 22 fetuses with cerebral anomalies. In 180 of 183 fetuses (98.4%), 5D CNS+ successfully reconstructed all of the diagnostic planes. Using the software on healthy fetuses, the observers acknowledged the presence of diagnostic images with visualization rates ranging from 97.7% to 99.4% for axial planes, 94.4% to 97.7% for sagittal planes, and 92.2% to 97.2% for coronal planes. The Cohen κ coefficient was analyzed to evaluate the agreement rates between the observers and resulted in values of 0.96 or greater for axial planes, 0.90 or greater for sagittal planes, and 0.89 or greater for coronal planes. All 22 fetuses with brain anomalies were identified among a series that also included healthy fetuses, and in 21 of the 22 cases, a correct diagnosis was made. 5D CNS+ was efficient in successfully imaging standard axial, sagittal, and coronal planes of the fetal brain. This approach may simplify the examination of the fetal central nervous system and reduce operator dependency.

First trimester placental volume and three dimensional power doppler ultrasonography in type I diabetic pregnancies.

OBJECTIVE: This study aimed to investigate the placental volume and three dimensional (3D) power Doppler vascularization in type I diabetic pregnancies during the first trimester METHODS: 3D-power Doppler ultrasonography of the placenta was performed at 11+0-13+6 weeks in 32 pregnancies complicated by type I diabetes. Placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated using a standardized setting. RESULTS: In nine pregnancies, a poor first trimester glycemic control was present as expressed by HbA1c levels ≥ 7%, whereas in the remaining 23 mothers, the HbA1c concentrations were <7%. No differences were found in the placental volumes of diabetic mothers when compared with reference limits. 3D Doppler placental vascular indices were significantly higher in diabetic mothers (VI delta value 0.99, p=0.0012; FI delta value 0.64, p=0.0008; VFI delta value 1.28, p=0.0039) when compared with reference limits. Pregnancies with HbA1c ≥ 7% exhibited higher placental vascular indices when compared with diabetic mothers with better glycemic control. CONCLUSIONS: In type I diabetic mothers, placental vascular indices are increased and these modifications are more evident in pregnancies with poor first trimester glycemic control.

Assessment of corpus callosum biometric measurements at 18 to 32 weeks' gestation by 3-dimensional sonography.

OBJECTIVES: The purposes of this study were to construct reference limits for corpus callosum dimensions measured on images reconstructed from 3-dimensional (3D) sonography and to evaluate the reproducibility of these measurements. METHODS: Three-dimensional sonographic volumes were acquired transabdominally from an axial view of the head in 361 fetuses cross-sectionally studied at 18 to 32 weeks' gestation. Offline analysis of the fetal brain midsagittal plane was used to evaluate the length and area of the corpus callosum and corpus callosum-cavum septi pellucidi complex. The agreement between 2-dimensional (2D) and 3D measurements as well as the interobserver variability in 3D measurements were assessed by interclass correlation coefficients (ICCs). RESULTS: Adequate visualization of the midsagittal plane was obtained in 98.1% of the fetuses. A clear distinction between the corpus callosum and cavum septi pellucidi was obtained in 35.7% of the fetuses, whereas in the remaining cases, the corpus callosum-cavum septi pellucidi complex was visualized as a single echogenic structure. The corpus callosum-cavum septi pellucidi complex length (r = 0.806; P < .0001), corpus callosum-cavum septi pellucidi complex area (r = 0.920; P < .0001), and corpus callosum area (r = 0.713; P < .0001) showed a significant linear growth with gestation. A good agreement was found between measurements from both 2D and 3D sonographic views (corpus callosum length ICC, 0.916) as well as between measurements obtained by different observers (corpus callosum-cavum septi pellucidi complex length ICC, 0.936; corpus callosum-cavum septi pellucidi complex area ICC, 0.931). CONCLUSIONS: Measurements of the corpus callosum and cavum septi pellucidi can be obtained from the midsagittal plane of the fetal brain reconstructed from 3D volumes acquired transabdominally. The constructed nomograms may facilitate the diagnosis of corpus callosum abnormalities.

Satisfactory rate of postprocessing visualization of standard fetal cardiac views from 4-dimensional cardiac volumes acquired during routine ultrasound practice by experienced sonographers in peripheral centers.

The aim of this study was to evaluate the feasibility of visualizing standard cardiac views from 4-dimensional (4D) cardiac volumes obtained at ultrasound facilities with no specific experience in fetal echocardiography. Five sonographers prospectively recorded 4D cardiac volumes starting from the 4-chamber view on 500 consecutive pregnancies at 19 to 24 weeks' gestation undergoing routine ultrasound examinations (100 pregnancies for each sonographer). Volumes were sent to the referral center, and 2 independent reviewers with experience in 4D fetal echocardiography assessed their quality in the display of the abdominal view, 4-chamber view, left and right ventricular outflow tracts, and 3-vessel and trachea view. Cardiac volumes were acquired in 474 of 500 pregnancies (94.8%). The 2 reviewers respectively acknowledged the presence of satisfactory images in 92.4% and 93.6% of abdominal views, 91.5% and 93.0% of 4-chamber views, in 85.0% and 86.2% of left ventricular outflow tracts, 83.9% and 84.5% of right ventricular outflow tracts, and 85.2% and 84.5% of 3-vessel and trachea views. The presence of a maternal body mass index of greater than 30 altered the probability of achieving satisfactory cardiac views, whereas previous maternal lower abdominal surgery did not affect the quality of reconstructed cardiac views. In conclusion, cardiac volumes acquired by 4D sonography in peripheral centers showed high enough quality to allow satisfactory diagnostic cardiac views.

Histomorphometric characteristics of first trimester chorionic villi in pregnancies with low serum pregnancy-associated plasma protein-A levels: relationship with placental three-dimensional power doppler ultrasonographic vascularization.

OBJECTIVE: To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization. METHODS: Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system. RESULTS: Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01). CONCLUSIONS: Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.

Umbilical vein blood flow at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To establish reference intervals for fetal umbilical vein (UV) diameter, UV time averaged maximum velocity (TAMXV) and UV flow (UVBF) at 11 + 0 to 13 plus; 6 weeks of gestation and to determine the intraobserver reliability of these measurements. METHODS: We considered, in a cross-sectional study, 162 fetuses from uncomplicated singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. UV diameter and TAMXV were measured in its intraabdominal portion by real-time and Doppler ultrasonography and UVBF calculated. Relationships between these parameters and fetal crown rump length were tested by regression analysis. In 25 cases UVBF was measured twice by the same investigator and the intraobserver agreement of these measurements was calculated. RESULTS: A significant increase was evidenced in the gestational age period considered in UV diameter (r = 0.729, p < 0.0001), TAMXV (r = 0.691, p < 0.0001) and UVBF (r = 0.777, p < 0.0001). UVBF increased from 2.26 ml/min at 11 weeks to 15.62 ml/min at 13 + 6 weeks of gestation. The intraobserver ICCs were 0.96, 0.92 and 0.88, respectively, for UV diameter, TAMXV and UVBF. CONCLUSIONS: In normal fetuses, UV diameter, TAMVX and flow increase between 11 + 0 and 13 + 6 weeks of gestation. In this gestational age interval, the calculation of UV blood flow and its components shows an intraobserver agreement reliable enough for clinical use.

Role of sonographic automatic volume calculation in measuring fetal cardiac ventricular volumes using 4-dimensional sonography: comparison with virtual organ computer-aided analysis.

OBJECTIVE: The purpose of this study was to compare the agreement and reliability of virtual organ computer-aided analysis (VOCAL) and sonographic automatic volume calculation (sonoAVC) for measurements of ventricular volume from fetal heart data sets acquired by 4-dimensional sonography with spatiotemporal image correlation (STIC). METHODS: We studied 45 volumes from fetuses with normal (n = 30) and abnormal (n = 15) hearts. Spatiotemporal image correlation data sets were frozen in end systole and end diastole, and ventricular volumes were measured with VOCAL and sonoAVC. The stroke volume was calculated from these measurements. Reliability and agreement of the two techniques were evaluated with intraclass correlation coefficients (ICCs), and proportionate Bland-Altman plots were constructed. The time necessary to complete the measurements with either technique was compared. Intraobserver and interobserver agreement of measurements was calculated. RESULTS: All data sets could be measured with both techniques. A high degree of reliability was observed between VOCAL and sonoAVC (left ventricular stroke volume ICC, 0.978; 95% confidence interval [CI], 0.957-0.989; right ventricular stroke volume ICC, 0.985; 95% CI, 0.972-0.992). The time necessary to measure the stroke volume was significantly shorter with sonoAVC (2.8 versus 11.7 minutes; P < .0001) than with VOCAL. Bland-Altman tests showed no clinically significant mean percent differences between stroke volume measurements obtained from each ventricle by the same observer or by 2 independent observers using either VOCAL or sonoAVC. CONCLUSIONS: There was good agreement between cardiac volumes measured with VOCAL and sonoAVC. Sonographic automatic volume calculation represents a rapid technique for estimating fetal stroke volume and promises to become the method of choice.

First-trimester placental volume and vascularization measured by 3-dimensional power Doppler sonography in pregnancies with low serum pregnancy-associated plasma protein a levels.

OBJECTIVE: The purpose of this study was to investigate the first-trimester placental volume and 3-dimensional (3D) power Doppler vascularization of pregnancies with low serum pregnancy-associated plasma protein A (PAPP-A) levels and to relate these findings to pregnancy outcomes. METHODS: Three-dimensional power Doppler sonography of the placenta was performed at gestational ages of 11 weeks to 13 weeks 6 days in 84 pregnancies with PAPP-A concentrations of less than 0.4 multiple of the median (MoM). With a standardized setting, the placental volume and vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were calculated and related to pregnancy outcomes. RESULTS: Pregnancy outcomes were as follows: 57 pregnancies with birth weights at or above the 10th percentile (group A), 16 pregnancies with birth weights below the 10th percentile and normal Doppler findings in the umbilical artery throughout gestation (group B), and 11 pregnancies with birth weights below the 10th percentile and abnormal umbilical Doppler findings later in gestation (group C). No differences were found in PAPP-A levels among groups. Placental volume values were significantly lower than reference limits, but no differences were found between groups. In groups A and B, there were no significant differences in 3D Doppler indices. However, these indices were significantly lower in group C (VI mean difference, -1.904; P < .001; FI mean difference, -1.939; P < .001; VFI mean difference, -1.944; P < .001). Placental vascular indices were significantly related to the severity of intrauterine growth restriction (IUGR; VI, r = 0.438; P < .001; FI, r = 0.482; P < .001; VFI, r = 0.497; P < .001) but not to the PAPP-A MoM and placental volume values. CONCLUSIONS: Low serum maternal PAPP-A levels are associated with altered 3D placental Doppler indices, and these changes are related to subsequent development of IUGR and adverse pregnancy outcomes.

The significance of visualising coronary blood flow in early onset severe growth restricted fetuses with reverse flow in the ductus venosus.

OBJECTIVE: To evaluate the incidence and significance of coronary blood flow visualisation in early onset severe intrauterine growth restriction (IUGR) fetuses and to assess its relationship with the presence of reverse flow in ductus venosus (DV). METHODS: The examination of coronary artery was performed at a gestational age <26 weeks in 19 IUGR fetuses from mothers without medical complications and characterised by the presence of reverse flow in DV. Visualisation or non-visualisation of coronary circulation were compared with fetal and neonatal outcome. RESULTS: Coronary flow was seen in 7/19 (36.8%) of the IUGR fetuses and these fetuses showed a higher incidence of fetal death (71.4%vs. 16.6%, p = 0.044), delivery or fetal death at an earlier gestational age (23.71 vs. 26.57 weeks, p = 0.011) and a lower birthweight (310 vs. 586 g, p = 0.011). Kaplan-Meier survival analysis demonstrated that visualisation or non-visualisation of coronary flow in such fetuses provides an independent contribution in the prediction of the time interval between Doppler study and delivery or fetal death (chi square = 15.36, p < 0.001). CONCLUSIONS: Visualisation of coronary flow in IUGR fetuses with reverse flow in the DV identifies a subgroup of fetuses with a poorer fetal and neonatal outcome.

Effects of maternal cigarette smoking on placental volume and vascularization measured by 3-dimensional power Doppler ultrasonography at 11+0 to 13+6 weeks of gestation.

OBJECTIVE: We sought to establish the effect of maternal smoking on placental volume and vascularization in early gestation. STUDY DESIGN: Three-dimensional power Doppler ultrasonography of the placenta was performed at 11+0 to 13+6 weeks in 80 pregnancies categorized according to cigarette consumption: group A never smoked, B smoking < 10 cigarettes/day, C smoking 10-20 cigarettes/day, and D smoking > 20 cigarettes/day. Using a standardized setting, placental volume and vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated. RESULTS: No differences were found in placental volume among groups. In groups C and D lower values were found for VI (group C: t = 4.52, P = .0002; group D: t = 3.72, P = .0014), FI (group C: t = 5.06, P = .0001; group D: t = 4.59, P = .0002), and VFI (group C: t = 3.49, P = .0024; group D: t = 2.88, P = .0095). Placental vascular indices were significantly related to birthweight (VI r = 0.563, FI r = 0.580, VFI r = 0.601; P < .001). CONCLUSION: Maternal smoking is associated with altered 3-dimensional placental Doppler indices and these changes are related to birth weight.

Relationship between aortic isthmus and ductus venosus velocity waveforms in severe growth restricted fetuses.

OBJECTIVE: To evaluate the incidence of abnormalities in velocity waveforms from ductus venosus (DV) and aortic isthmus (AoI) in fetuses with intrauterine growth restriction (IUGR) and their reciprocal temporal relationship. METHODS: DV and AoI velocity waveforms were recorded in 31 IUGR fetuses characterized either by absent end diastolic (20) or reverse flow (11) in umbilical artery. Abnormal velocity waveforms in DV and AoI were defined in presence of reverse diastolic flows. RESULTS: Abnormal DV velocity waveforms were present in 10 fetuses and were always associated with abnormalities. Abnormal AoI flows were also present in 10 fetuses of the remaining 21 fetuses with normal DV velocity waveforms (47.6%). Longitudinal monitoring of fetuses with normal DV flows showed a significantly shorter time interval in the onset of reverse flow in DV when abnormalities in AoI were present (4 vs 14 days p=0.001) irrespectively of gestational age or other potential confounding variables. CONCLUSIONS: Our data suggest that AoI velocity waveforms become abnormal at an earlier stage of fetal compromise than DV.

Use of the 3-vessel view to record Doppler velocity waveforms from the aortic isthmus in normally grown and growth-restricted fetuses: comparison with the long aortic arch view.

OBJECTIVE: Aortic isthmus (AoI) velocity waveforms are considered powerful indicators of hemodynamic deterioration in intrauterine growth-restricted (IUGR) fetuses. However, technical difficulties in sampling AoI velocity waveforms from the longitudinal aortic arch (LAA) have limited its clinical application thus far. In this study, we tested the possibility of recording AoI velocity waveforms from the 3-vessel (3V) view of the fetal mediastinum and comparing the agreement of these measurements with recordings from the LAA. METHODS: Doppler measurements of the pulsatility index (PI) from the AoI were performed in 70 fetuses (20 IUGR and 50 normally grown) between 20 and 34 weeks' gestation. All measurements were sampled in both the LAA and 3V views by the same investigator. Reliability was evaluated with intraclass correlation coefficients (ICCs), and Bland-Altman plots were generated. The time required to complete the measurements was compared. RESULTS: A high degree of reliability was observed between PI values obtained from LAA and 3V views in both IUGR and normally grown fetuses (all fetuses: ICC, 0.976; 95% confidence interval [CI], 0.961-0.985; normally grown: ICC, 0.839; 95% CI, 0.731-0.906; IUGR: ICC, 0.954; 95% CI, 0.886-0.982). However, recordings from the 3V view were significantly less time-consuming than those from the LLA view (mean +/- SD, 30.4 +/- 14.2 versus 52.8 +/- 29.4 seconds; P < .0001) and showed higher intraobserver reproducibility. CONCLUSIONS: In IUGR and normally grown fetuses, AoI waveforms can be reliably obtained from the 3V view with higher reproducibility and a shorter recording time.

Examination of the fetal heart by four-dimensional ultrasound with spatiotemporal image correlation during routine second-trimester examination: the 'three-steps technique'.

OBJECTIVE: To prospectively analyze the accuracy and rapidity of four-dimensional (4D) ultrasonography with spatiotemporal image correlation (STIC) in the assessment of four-chamber view and outflow tracts in unselected fetuses and in fetuses with congenital heart defects (CHD) at 19-23 weeks of gestation. MATERIALS AND METHODS: 112 consecutive pregnancies undergoing routine second-trimester ultrasonographic scan and 10 pregnancies with fetuses with CHD affecting the great arteries formed the study group. From the four-chamber view, volumes of the fetal heart were acquired by the STIC technique and stored for a later offline analysis that was performed by two examiners blinded to the characteristics of the fetuses. Offline analysis was performed using a simplified multiplanar approach based on 3 different steps and one rotation finalized to visualize the four-chamber view and the left and right outflow tracts. RESULTS: Adequate recognition of four-chamber view and outflow tracts was obtained in more than 80% of the volumes. There were no false-positives and only one observer had a false-negative (interrupted aortic arch classified as normal). The mean time required to interpret 4D volumes was 3.7 min. CONCLUSIONS: The standard fetal cardiac anatomy survey can be performed in the second-trimester fetus by 4D STIC in both normal and abnormal hearts. This approach may reduce the operator's dependency in diagnosis of CHD.

Role of tomographic ultrasound imaging with spatiotemporal image correlation for identifying fetal ventricular septal defects.

OBJECTIVE: The purpose of this study was to test the possibility of diagnosing ventricular septal defects (VSDs) by using tomographic ultrasound imaging (TUI) on 4-dimensional volumes of the fetal chest obtained with spatiotemporal image correlation and the color Doppler function. METHODS: We retrospectively evaluated the 4-dimensional spatiotemporal image correlation volumes of 8 fetuses with VSDs (single in 7 and double in 1) between 20 and 33 weeks' gestation. The data were analyzed to determine whether VSDs were correctly identified in at least 1 of 7 automatically generated TUI displays. RESULTS: All of the included VSDs were correctly identified with the use of an interslice distance in the TUI function ranging from 0.8 to 2 mm without the need to further manipulate the volume. CONCLUSIONS: This automatic approach shows good retrieval of diagnostic cardiac planes in fetuses with VSDs, which may improve the diagnostic accuracy for this disease.

Application of automated sonography on 4-dimensional volumes of fetuses with transposition of the great arteries.

OBJECTIVE: The purpose of this study was to assess, in second-trimester fetuses with transposition of the great arteries (TGA), the performance of software (sonographically based volume computer-aided analysis) that automatically retrieves diagnostic cardiac planes from a 4-dimensional volume of the fetal chest obtained with spatiotemporal image correlation. METHODS: We retrospectively evaluated the 4-dimensional spatiotemporal image correlation volumes of 12 fetuses with TGA (complete TGA, 10 cases; correct TGA, 2 cases). The data were analyzed to determine whether the target diagnostic planes, that is, cardiac plane 1 (left ventricle outflow tract) and cardiac plane 2 (right ventricle outflow tract), were correctly identified in at least 1 of the 7 automatically generated tomographic sonographic image displays and whether they allowed diagnosis of TGA. RESULTS: In 9 of 10 fetuses with complete TGA, target diagnostic cardiac plane 1 showed a branching arterial vessel (pulmonary artery) arising from the left ventricle, whereas in 7 of 10 fetuses, the aorta arising from the right ventricle was shown. In both cases with correct TGA, the pulmonary artery starting from the morphologic left ventricle was shown, whereas in 1 of 2, the connection of the aorta with the morphologic right ventricle was found. In all of the fetuses with TGA, a ventricular arterial connection anomaly was shown in either cardiac plane 1 or 2. CONCLUSIONS: This automatic approach shows good retrieval of diagnostic cardiac planes in fetuses with TGA, which may improve diagnostic efficacy for this disease.