Three-Dimensional Fractional Moving Blood Volume (3D-FMBV): A robust bedside tool for evaluation of fetal multi-organ perfusion.

INTRODUCTION: Three-dimensional-fractional moving blood volume (3D-FMBV) may provide superior non-invasive measurement of feto-placental perfusion compared to current methods. This study investigated the feasibility and repeatability of producing 3D-FMBV measurements of the placenta, fetal liver, kidney, and brain in a single ultrasound consultation. METHODS: The placenta, fetal liver, kidney and brain were scanned in triplicate using 3D power Doppler ultrasound (3D-PDU) in 48 women ≥22 weeks gestation with healthy fetuses. 3D-FMBV was calculated by two analyzers. Feasibility was assessed as the percentage of cases where 3D-FMBV could be evaluated; repeatability (intraobserver and interobserver) using two-way mixed measure intraclass correlation coefficients (ICCs). RESULTS: 3D-FMBV was calculated for 100% of scanned organs. Intraobserver ICCs (95% CI) were good to excellent; 0.93 (0.88-0.96) and 0.87 (0.78-0.92) for placenta, 0.95 (0.92-0.97) and 0.98 (0.96-0.99) for fetal liver, 0.96 (0.94-0.98) and 0.91 (0.85-0.95) for fetal kidney and 0.98 (0.97-0.99) and 0.97 (0.95-0.98) for fetal brain. Interobserver ICCs (95% CI) were 0.50 (0.08-0.73), 0.92 (0.85-0.96), 0.89 (0.78-0.94) and 0.71 (0.46-0.85) for placenta, fetal liver, kidney and brain. CONCLUSION: Feto-placental perfusion assessment with 3D-FMBV is highly reliable in healthy pregnancies ≥22 weeks gestation and can be feasibly calculated in four feto-placental vascular beds in a single ultrasound consultation.

Evaluation of neonatal cerebral perfusion using three-dimensional power Doppler ultrasound volumes.

AIM: Despite improvement in preterm survival, neurological morbidity remains high. 3D fractional moving blood volume (3D-FMBV) quantifies neonatal cerebral perfusion by calculating a standardised measure of the amount of moving blood in a region of interest and correlates with tissue perfusion in animal studies. However, its feasibility and reproducibility are yet to be assessed in newborn infants. METHODS: Fractional moving blood volume analysis was performed on three-dimensional power Doppler ultrasound (PD-US) volumes from a cohort of preterm infants recruited in 2015 from the Royal Hospital for Women Neonatal Intensive Care Unit. The volumes were acquired by two sonographers and analysed by two different observers. The 3D-FMBV algorithm was applied to calculate an estimate for perfusion. Reproducibility and agreement were assessed using intra-class correlation coefficients (ICC) and Bland-Altman plots. RESULTS: All 3D PD-US volumes were analysed successfully. Intra-observer reliability was excellent with an ICC of 0.907 (95% CI 0.751-0.968) and 0.906 (95% CI 0.741-0.967) for two independent observers respectively. The inter-observer reliability of the entire technique was good with an ICC of 0.752 (CI: 0.404-0.909). CONCLUSION: We have successfully shown the feasibility and reliability of applying the 3D-FMBV technique to the neonatal brain in a healthy preterm population.

The Influence of Hyperoxygenation on Fetal Brain Vascularity Measured Using 3D Power Doppler Ultrasound and the Index "Fractional Moving Blood Volume".

INTRODUCTION: Maternal hyperoxygenation effects on fetal cerebral hemodynamics are largely unknown. This study aimed to determine efficacy and reliability of a validated power Doppler ultrasound (US) index, fractional moving blood volume (FMBV), at measuring fetal cerebral vasculature changes during maternal hyperoxia. METHODS: The fetal cerebral effects of 10 min of hyperoxygenation at 2 flow rates (52%/60% FiO2) were evaluated in women in their third trimester of pregnancy. 2D-US and 3D-US in a transverse plane were performed before, during, and following maternal hyperoxygenation with FMBV estimation performed offline. RESULTS: Forty-five cases provided data for analysis. Mean intraobserver ICCs were 0.89 (3D-FMBV) and 0.84 (2D-FMBV). A significant difference in vascularity before and during and before and after 60% hyperoxia was observed (p < 0.05), whereas no significant differences were found at 52% hyperoxia (p > 0.05). Significant differences in vascularity were found between 2D-FMBV and 3D-FMBV (p < 0.01). CONCLUSION: Measurement of fetal cerebral vascularity by 3D-FMBV and 2D-FMBV was highly reproducible. The differing cerebral vascular changes seen with 60% but not 52% FiO2 suggest a possible "threshold effect" that may have influenced prior studies. Further studies are needed to assess cerebral effects of maternal hyperoxygenation on compromised fetuses.

Three-dimensional US Fractional Moving Blood Volume: Validation of Renal Perfusion Quantification.

Background Three-dimensional (3D) fractional moving blood volume (FMBV) derived from 3D power Doppler US has been proposed for noninvasive approximation of perfusion. However, 3D FMBV has never been applied in animals against a ground truth. Purpose To determine the correlation between 3D FMBV and the reference standard of fluorescent microspheres (FMS) for measurement of renal perfusion in a porcine model. Materials and Methods From February 2017 to September 2017, adult pigs were administered FMS before and after measurement of renal 3D FMBV at baseline (100%) and approximately 75%, 50%, and 25% flow levels by using US machines from two different vendors. The 3D power Doppler US volumes were converted and segmented, and correlations between FMS and 3D FMBV were made with simple linear regression (r2). Similarity and reproducibility of manual segmentation were determined with the Dice similarity coefficient and 3D FMBV reproducibility (intraclass correlation coefficient [ICC]). Results Thirteen pigs were studied with 33 flow measurements. Kidney volume (mean Dice similarity coefficient ± standard deviation, 0.89 ± 0.01) and renal segmentation (coefficient of variation = 12.6%; ICC = 0.86) were consistent. The 3D FMBV calculations had high reproducibility (ICC = 0.97; 95% confidence interval: 0.96, 0.98). The 3D FMBV per-pig correlation showed excellent correlation for US machines from both vendors (mean r2 = 0.96 [range, 0.92-1.0] and 0.93 [range, 0.78-1.0], respectively). The correlation between 3D FMBV and perfusion measured with microspheres was high for both US machines (r2 = 0.80 [P < .001] and 0.70 [P < .001], respectively). Conclusion The strong correlation between three-dimensional (3D) fractional moving blood volume (FMBV) and fluorescent microspheres indicates that 3D FMBV shows excellent correlation to perfusion and good reproducibility. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Morrell et al in this issue.

Basal ganglia perfusion in the preterm infant during transition.

BACKGROUND: The preterm brain is susceptible to changes in blood flow. Using power Doppler images, digital imaging techniques have been developed to measure the total amount of blood flow in a defined area, giving the index: fractional moving blood volume (FMBV). The aim of this study was to investigate temporal changes in basal ganglia perfusion during the transitional period after birth. METHODS: Twenty-four preterm infants were examined with serial cranial ultrasounds at four time points during the first 48 h of life. FMBV was calculated using power Doppler images at each time point. RESULTS: All infants had analyzable data and FMBV was successfully calculated at all time points. Twenty-three of the 24 infants had an increasing trend in FMBV over time. The median FMBV increased from 17% at 6 h to 25% at 48 h. One-way repeated measures ANOVA showed a significant increase in values at P < 0.001 at each of the four time points. CONCLUSION: We have demonstrated changes in basal ganglia blood flow as the cerebral circulation adapts to extrauterine life. With further investigation, this technique may be useful in the assessment of preterm circulatory adaptation, either alone or in conjunction with other modes of evaluating cerebral blood flow.

A technique for the estimation of fractional moving blood volume by using three-dimensional power Doppler US.

PURPOSE: To (a) demonstrate an image-processing method that can automatically measure the power Doppler signal in a three-dimensional ( 3D three-dimensional ) ultrasonographic (US) volume by using the location of organs within the image and (b) compare 3D three-dimensional fractional moving blood volume ( FMBV fractional moving blood volume ) results with commonly used, unstandardized measures of 3D three-dimensional power Doppler by using the human placenta as the organ of interest. MATERIALS AND METHODS: This is a retrospective study of scans obtained as part of a prospective study of imaging placental biomarkers with US, performed with ethical approval and written informed consent. One hundred forty-three consecutive female patients were examined by using an image-processing technique. Three-dimensional FMBV fractional moving blood volume was measured on the vasculature from the uteroplacental interface to a depth 5 mm into the placenta by using a normalization volume 10 mm outside the uteroplacental interface and compared against the Virtual Organ Computer-aided AnaLysis ( VOCAL Virtual Organ Computer-aided AnaLysis ; GE Healthcare, Milwaukee, Wis) vascularization flow index ( VFI vascularization flow index ). Intra- and interobserver variability was assessed in a subset of 18 volumes. Wilcoxon signed rank test and intraclass correlation coefficients were used to assess measurement repeatability. RESULTS: The mean 3D three-dimensional FMBV fractional moving blood volume value ± standard deviation was 11.78% ± 9.30 (range, 0.012%-44.16%). Mean VFI vascularization flow index was 2.26 ± 0.96 (range, 0.15-6.06). Linear regression of VFI vascularization flow index versus FMBV fractional moving blood volume produced an R(2) value of 0.211 and was significantly different in distribution (P < .001). Intraclass correlation coefficient analysis showed higher FMBV fractional moving blood volume values than VFI vascularization flow index for intra- and interobserver variability; intraobserver values were 0.95 for FMBV fractional moving blood volume (95% confidence interval [ CI confidence interval ]: 0.90, 0.98) versus 0.899 for VFI vascularization flow index (95% CI confidence interval : 0.78, 0.96), and interobserver values were 0.93 for FMBV fractional moving blood volume (95% CI confidence interval : 0.82, 0.97) versus 0.67 for VFI vascularization flow index (95% CI confidence interval : 0.32, 0.86). CONCLUSION: The extension of an existing two-dimensional standardized power Doppler measurement into 3D three-dimensional by using an image-processing technique was shown in an in utero placental study. Three-dimensional FMBV fractional moving blood volume and VFI vascularization flow index produced significantly different results. FMBV fractional moving blood volume performed better than VFI vascularization flow index in repeatability studies. Further studies are needed to assess accuracy against a reference standard.

Monitoring of Cerebrovascular Reactivity for Determination of Optimal Blood Pressure in Preterm Infants.

OBJECTIVE: To define levels of mean arterial blood pressure (MABP) where cerebrovascular reactivity is strongest in preterm infants (ie, optimal MABP, or MABPOPT) and correlate deviations from MABPOPT with mortality and intraventricular hemorrhage (IVH). STUDY DESIGN: A total of 60 preterm infants born at median gestational age 26 ± 2 weeks (23 ± 2 to 32 ± 1) with indwelling arterial catheter were studied at a median 34 hours (range 5-228) of age. Tissue oxygenation heart rate (HR) reactivity index, which estimates cerebrovascular reactivity, was calculated as the moving correlation coefficient between slow waves of tissue oxygenation index, measured with near-infrared spectroscopy, and HR. MABPOPT was defined by dividing MABP into 2-mm Hg bins and averaging the tissue oxygenation HR reactivity index within those bins. A measurement of divergence from MABPOPT was calculated as the absolute difference between mean MABP and mean MABPOPT. RESULTS: Individual MABPOPT was defined in 81% of the patients. A measurement of divergence from MABPOPT was greater in those patients who died (mean 4.2 mm Hg; 95% CI 3.33-4.96) compared with those who survived (mean 2.1 mm Hg; 95% CI 1.64-2.56), P = .013. Patients who had MABP lower than MABPOPT by 4 mm Hg or more had a greater rate of mortality (40%) than those with MABP close to or above MABPOPT (13%), P = .049. Patients with MABP greater than MABPOPT by 4 mm Hg had greater IVH scores, P = .042. CONCLUSIONS: Continuous monitoring of cerebrovascular reactivity allows the determination of MABPOPT in preterm neonates. Significant deviation below MABPOPT was observed in infants who died. Deviation of MABP above optimal level was observed in infants who developed more severe IVH.

Does matrix transducer technology improve quality and repeatability of four-dimensional tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements?

Background: Novel ultrasound technology and software processing allow offline evaluation of tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements. We wished to compare both novel 4D matrix (eM6C) and conventional (RAB6-D) transducers with variable settings (electronic spatiotemporal image correlation, spatiotemporal image correlation and four-dimensional real time) to determine if there was a significant difference in absolute value, quality and repeatability of the resultant reconstructed image and M-mode trace. Methods: A blinded prospective cross-sectional study of normal fetuses from 23 to 38 weeks' gestation were recruited. After routine sonography, four-dimensional volumes were stored and analysed using GE 4DView™ software. Statistical analysis explored variability, correlations and repeatability of the measurements with chi-square analysis, intraclass correlations and the Bland-Altman comparison plots. A scoring system was devised for image quality. Results: Eighteen participants generated 282 data volumes. Absolute values demonstrated some inconsistencies for both tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements with variations between transducers: the highest for the RAB6-D/spatiotemporal image correlation setting and the lowest for the four-dimensional real-time settings. The RAB6-D/spatiotemporal image correlation setting was the most repeatable combination (intraclass correlation coefficient = 0.85). Poorest image quality (M-mode trace, four-chamber view, annuli) came from the RAB6-D/four-dimensional real-time combination with the eM6C/electronic spatiotemporal image correlation and RAB6-D/spatiotemporal image correlation settings being nearly identical. Conclusion: We show that transducer and setting combinations influence absolute tricuspid annular plane systolic excursion/mitral annular plane systolic excursion measurements, so need to be articulated in future research. The transducer setting (electronic spatiotemporal image correlation/spatiotemporal image correlation/four-dimensional real time) was a more significant factor than the type of transducer (conventional vs matrix). Subjective image evaluation does not correlate well with repeatability of image acquisition. Further studies are needed to compare measurements using four-dimensional post-processing tools against conventional real-time measurements.

Insight into evolution of Bordetella pertussis from comparative genomic analysis: evidence of vaccine-driven selection.

Despite high vaccine coverage, pertussis incidence has increased substantially in recent years in many countries. A significant factor that may be contributing to this increase is adaptation to the vaccine by Bordetella pertussis, the causative agent of pertussis. In this study, we first assessed the genetic diversity of B. pertussis by microarray-based comparative genome sequencing of 10 isolates representing diverse genotypes and different years of isolation. We discovered 171 single nucleotide polymorphisms (SNPs) in a total of 1.4 Mb genome analyzed. The frequency of base changes was estimated as one per 32 kb per isolate, confirming that B. pertussis is one of the least variable bacterial pathogens. We then analyzed an international collection of 316 B. pertussis isolates using a subset of 65 of the SNPs and identified 42 distinct SNP profiles (SPs). Phylogenetic analysis grouped the SPs into six clusters. The majority of recent isolates belonged to clusters I-IV and were descendants of a single prevaccine lineage. Cluster I appeared to be a major clone with a worldwide distribution. Typing of genes encoding acellular vaccine (ACV) antigens, ptxA, prn, fhaB, fim2, and fim3 revealed the emergence and increasing incidence of non-ACV alleles occurring in clusters I and IV, which may have been driven by ACV immune selection. Our findings suggest that B. pertussis, despite its high population homogeneity, is evolving in response to vaccination pressure with recent expansion of clones carrying variants of genes encoding ACV antigens.

Effect of malaria on placental volume measured using three-dimensional ultrasound: a pilot study.

BACKGROUND: The presence of malaria parasites and histopathological changes in the placenta are associated with a reduction in birth weight, principally due to intrauterine growth restriction. The aim of this study was to examine the feasibility of studying early pregnancy placental volumes using three-dimensional (3D) ultrasound in a malaria endemic area, as a small volume in the second trimester may be an indicator of intra-uterine growth restriction and placental insufficiency. METHODS: Placenta volumes were acquired using a portable ultrasound machine and a 3D ultrasound transducer and estimated using the Virtual Organ Computer-aided AnaLysis (VOCAL) image analysis software package. Intra-observer reliability and limits of agreement of the placenta volume measurements were calculated. Polynomial regression models for the mean and standard deviation as a function of gestational age for the placental volumes of uninfected women were created and tested. Based on these equations each measurement was converted into a z -score. The z-scores of the placental volumes of malaria infected and uninfected women were then compared. RESULTS: Eighty-four women (uninfected = 65; infected = 19) with a posterior placenta delivered congenitally normal, live born, single babies. The mean placental volumes in the uninfected women were modeled to fit 5th, 10th, 50th, 90th and 95th centiles for 14-24 weeks' gestation. Most placenta volumes in the infected women were below the 50th centile for gestational age; most of those with Plasmodium falciparum were below the 10th centile. The 95% intra-observer limits of agreement for first and second measurements were ± 37.0 mL and ± 25.4 mL at 30 degrees and 15 degrees rotation respectively. CONCLUSION: The new technique of 3D ultrasound volumetry of the placenta may be useful to improve our understanding of the pathophysiological constraints on foetal growth caused by malaria infection in early pregnancy.

Multi-Parametric Fusion of 3D Power Doppler Ultrasound for Fetal Kidney Segmentation Using Fully Convolutional Neural Networks.

Kidney development is key to the long-term health of the fetus. Renal volume and vascularity assessed by 3D ultrasound (3D-US) are known markers of wellbeing, however, a lack of real-time image segmentation solutions preclude these measures being used in a busy clinical environment. In this work, we aimed to automate kidney segmentation using fully convolutional neural networks (fCNNs). We used multi-parametric input fusion incorporating 3D B-Mode and power Doppler (PD) volumes, aiming to improve segmentation accuracy. Three different fusion strategies and their performance were assessed versus a single input (B-Mode) network. Early input-level fusion provided the best segmentation accuracy with an average Dice similarity coefficient (DSC) of 0.81 and Hausdorff distance (HD) of 8.96 mm, an improvement of 0.06 DSC and reduction of 1.43 mm HD compared to our baseline network. Compared to manual segmentation for all models, repeatability was assessed by intra-class correlation coefficients (ICC) indicating good to excellent reproducibility (ICC 0.93). The framework was extended to support multiple graphics processing units (GPUs) to better handle volumetric data, dense fCNN models, batch normalization and complex fusion networks. This work and available source code provides a framework to increase the parameter space of encoder-decoder style fCNNs across multiple GPUs and shows that application of multi-parametric 3D-US in fCNN training improves segmentation accuracy.

Fully Automated 3-D Ultrasound Segmentation of the Placenta, Amniotic Fluid, and Fetus for Early Pregnancy Assessment.

Volumetric placental measurement using 3-D ultrasound has proven clinical utility in predicting adverse pregnancy outcomes. However, this metric cannot currently be employed as part of a screening test due to a lack of robust and real-time segmentation tools. We present a multiclass (MC) convolutional neural network (CNN) developed to segment the placenta, amniotic fluid, and fetus. The ground-truth data set consisted of 2093 labeled placental volumes augmented by 300 volumes with placenta, amniotic fluid, and fetus annotated. A two-pathway, hybrid (HB) model using transfer learning, a modified loss function, and exponential average weighting was developed and demonstrated the best performance for placental segmentation (PS), achieving a Dice similarity coefficient (DSC) of 0.84- and 0.38-mm average Hausdorff distances (HDAV). The use of a dual-pathway architecture improved the PS by 0.03 DSC and reduced HDAV by 0.27 mm compared with a naïve MC model. The incorporation of exponential weighting produced a further small improvement in DSC by 0.01 and a reduction of HDAV by 0.44 mm. Per volume inference using the FCNN took 7-8 s. This method should enable clinically relevant morphometric measurements (such as volume and total surface area) to be automatically generated for the placenta, amniotic fluid, and fetus. The ready availability of such metrics makes a population-based screening test for adverse pregnancy outcomes possible.

Feasibility of image registration and fusion for evaluation of structure and perfusion of the entire second trimester placenta by three-dimensional power Doppler ultrasound.

BACKGROUND: Placental perfusion can be evaluated by 3D power Doppler ultrasound (3D PD-US), particularly using the validated tool 3D Fractional Moving Blood Volume (3D-FMBV); however regional variability and size limitations beyond the first trimester mean that multiple 3D PD-US volumes are required to evaluate the whole organ. PURPOSE: We assessed the feasibility of manual offline stitching of second trimester 3D PD-US volumes of the placenta to assess whole organ perfusion using 3D-FMBV. MATERIALS AND METHODS: This was a single-centre, prospective, observational cohort study of 36 normal second trimester singleton pregnancies with anterior placentas. 3D PD-US placental volumes were manually segmented offline and stitched together by rigid registration using manually selected, pair-wise coordinates. Data acquisition and offline volume segmentation and stitching were triplicated by a single observer with Dice similarity coefficient (DSC) and Hausdorff distance used to assess consistency. Intraclass correlation coefficient (ICC) was used to assess intra-observer repeatability of 3D-FMBV and placental volume. RESULTS: Acquisition and stitching success were 94% and 88%, respectively. Median time for acquisition, segmentation and stitching were 13 min, 40 min and 95 min, respectively. Median intra-observer DSCs were 0.94 and 0.88, and Hausdorff distances were 11.85 mm and 36.6 mm, for segmentations and stitching, respectively. CONCLUSION: 3D-ultrasound volume stitching of the placenta is technically feasible. Intra-observer repeatability was good to excellent for all measured parameters. This work demonstrates technical feasibility; further studies may provide the basis of an in-vivo assessment tool to measure the placenta in mid-to late pregnancy.

3D ultrasound file reading and coordinate transformations.

The Kretzfile format is used to store 3D ultrasound data, from GE Voluson ultrasound scanners. The geometry used in these hies is a toroidal coordinate system. Cartesian coordinates are required to allow application of advanced image libraries like ITK and scikit-image. We present ITK transformation and utilities to convert Kretzfiles to cartesian coordinates. Previous work (SlicerHeart, 2017) has enabled the reading of kretz files and approximate coordinate transformations. This work will enable medical imaging researchers to investigate clinically 3D ultrasound.

Four-Dimensional Ultrasound for Evaluating Newborn Cardiac Output: A Pilot Study of Healthy Infants.

BACKGROUND: There is currently no reliable non-invasive method of measuring cardiac output in neonatal intensive care. Spatiotemporal image correlation (STIC) is a novel four-dimensional (4D) ultrasound technique that was developed to assess the foetal heart, and it may be a useful way to assess neonatal haemodynamics. OBJECTIVE: This study aimed to evaluate the feasibility and reproducibility of determining neonatal cardiac output using STIC ultrasound in newborn infants. DESIGN: Infants were recruited opportunistically from a neonatal intensive care unit and then examined by 2 independent observers. STIC was used to obtain images of the heart. End-diastolic and end-systolic ventricular volumes were measured using virtual organ computer-aided analysis (VOCAL) and used to calculate cardiac output. Reproducibility was assessed with intraclass correlation coefficients (ICC) and agreement with Bland-Altman analysis. RESULTS: Twenty-four clinically stable infants of 34-43 weeks corrected gestational age were assessed. Both observers successfully acquired 4D STIC volumes in all infants. Left ventricular output showed good reproducibility, with an intra-observer ICC of 0.86 (0.69-0.94) and inter-observer ICC of 0.87 (0.70-0.95). Right ventricular output also showed good reproducibility, with an intra-observer ICC of 0.88 (0.70-95) and inter-observer ICC of 0.84 (0.63-0.93). CONCLUSIONS: Determining cardiac output using 4D STIC ultrasound is feasible and reproducible in well newborn infants. With further evaluation, this technique may provide valuable information about haemodynamic status in newborn infants requiring intensive care.

Determination of glycosyltransferase specificities for the Escherichia coli O111 O antigen by a generic approach.

We describe a bacterial strain developed to facilitate the determination of glycosyltransferase (GT) specificities for O antigens of known structure and gene cluster sequence. For proof of principle for the approach, the strain was used to determine the specificity of the Escherichia coli O111 O-antigen GT genes.

Understanding abnormal uterine artery Doppler waveforms: A novel computational model to explore potential causes within the utero-placental vasculature.

INTRODUCTION: Uterine artery (UtA) Doppler indices are one of the most commonly employed screening tests for pre-eclampsia worldwide. Abnormal indices appear to result from increased uterine vascular resistance, but anatomical complexity and lack of appropriate animal models mean that little is known about the relative contribution of each of the components of the uterine vasculature to the overall UtA Doppler waveform. Previous computational models suggested that trophoblast-mediated spiral artery remodeling has a dominant effect on the UtA Doppler waveform. However, these models did not incorporate the myometrial arterio-venous anastomoses, which have significant potential to affect utero-placental haemodynamics. METHODS: We present a more anatomically complete computational model, explicitly incorporating a structural description of each component of the uterine vasculature, and crucially including myometrial arterio-venous anastomoses as parallel pathways for blood-flow away from the placental bed. Wave transmission theory was applied to the network to predict UtA waveforms. RESULTS: Our model shows that high UtA resistance indices, combined with notching, reflect an abnormal remodeling of the entire uterine vasculature. Incomplete spiral artery remodeling alone is unlikely to cause abnormal UtA Doppler waveforms as increased resistance in these arteries can be 'buffered' by upstream anastomoses. Critically, our results indicate that the radial arteries, may have a more important effect on utero-placental flow dynamics, and the UtA Doppler waveform than previously thought. CONCLUSIONS: This model suggests that to appropriately interpret UtA Doppler waveforms they must be considered to be reflecting changes in the entire system, rather than just the spiral arteries.

Applying spatial-temporal image correlation to the fetal kidney: Repeatability of 3D segmentation and volumetric impedance indices.

INTRODUCTION: Spatiotemporal image correlation (STIC) can evaluate fetal renal impedance using four-dimensional volumetric indices. We assessed repeatability of three-dimensional kidney segmentation and the repeatability of the resultant indices. METHODS: In each of 57 healthy pregnant women, three renal artery pulsed-wave Doppler (PWD) traces and three STIC volumes were acquired from the same fetal kidney and segmented by two observers. Vascularisation-flow index (VFI) and fractional moving blood volume (FMBV) were calculated for every STIC frame and used to determine the volumetric pulsatility index (vPI), volumetric resistance index (vRI) and volumetric systolic/diastolic ratio (vS/D). Segmentation performance was assessed using Dice similarity coefficients (DSCs), Hausdorff distances, coefficient of variation (CoV) and the intraclass correlation coefficient (ICC). Intra/Inter volumetric index repeatability was assessed using ICCs. RESULTS: Forty-eight cases (84%) provided full data. Mean intra- and interobserver DSCs were 0.90 and 0.81. Mean intra- and interobserver Hausdorff distances were 3.88 mm and 5.27 mm. Average kidney volumes for observers 1 and 2 were 9.88 mL and 8.54 mL (mean difference 16.1%). Mean intra-observer volumetric CoVs were 5.3% and 8.1%. Intra- and interobserver ICCs for kidney volume (same STIC volume) were 0.97 and 0.85. When assessing volume variation between STIC volumes, intra-observer ICC was 0.97. ICCs were 0.77-0.81 for VFI-derived volumetric indices and 0.61-0.62 for FMBV-derived indices; ICCs for all PWD indices were between 0.58 and 0.59. CONCLUSIONS: Periodical variation in vascularity was demonstrated in the fetal kidney, and three-dimensional segmentation was highly repeatable. Derived volumetric impedance indices show moderate variability but outperform corresponding two-dimensional PWD indices in terms of reproducibility.

Automated Visualization and Quantification of Spiral Artery Blood Flow Entering the First-Trimester Placenta, Using 3-D Power Doppler Ultrasound.

The goal of our research was to quantify the placental vascularity in 3-D at 11-13 + 6 wk of pregnancy at precise distances from the utero-placental interface (UPI) using 3-D power Doppler ultrasound. With this automated image analysis technique, differences in vascularity between normal and pathologic pregnancies may be observed. The algorithm was validated using a computer-generated image phantom and applied retrospectively in 143 patients. The following features from the PD data were recorded: The number of spiral artery jets into the inter-villous space, total geometric and PD area. These were automatically measured at discrete millimeter distances from the UPI. Differences in features were compared with pregnancy outcomes: Pre-eclamptic versus normal, all small-for-gestational age (SGA) to appropriate-for-gestational age (AGA) patients and AGA versus SGA in normotensives (Mann-Whitney). The Benjamini-Hochberg procedure was used (false discovery rate 10%) for multiple comparison testing. Features decreased with increasing distance from the UPI (Kruskal-Wallis test; p <0.001). At 2- 3 mm from the UPI, all features were smaller in pre-eclamptic compared with normal patients and for some in SGA compared with AGA patients (p <0.05). For AGA versus SGA in normotensive patients, no significant differences were found. Number of jets measured at 2-5 mm from the UPI did not vary because of the position of the placenta in the uterus (ANOVA; p > 0.05). This method provides a new in-vivo imaging tool for examining spiral artery development through pregnancy. Size and number of entrances of blood flow into the UPI could potentially be used to identify high-risk pregnancies and may provide a new imaging biomarker for placental insufficiency.

Fully automated, real-time 3D ultrasound segmentation to estimate first trimester placental volume using deep learning.

We present a new technique to fully automate the segmentation of an organ from 3D ultrasound (3D-US) volumes, using the placenta as the target organ. Image analysis tools to estimate organ volume do exist but are too time consuming and operator dependant. Fully automating the segmentation process would potentially allow the use of placental volume to screen for increased risk of pregnancy complications. The placenta was segmented from 2,393 first trimester 3D-US volumes using a semiautomated technique. This was quality controlled by three operators to produce the "ground-truth" data set. A fully convolutional neural network (OxNNet) was trained using this ground-truth data set to automatically segment the placenta. OxNNet delivered state-of-the-art automatic segmentation. The effect of training set size on the performance of OxNNet demonstrated the need for large data sets. The clinical utility of placental volume was tested by looking at predictions of small-for-gestational-age babies at term. The receiver-operating characteristics curves demonstrated almost identical results between OxNNet and the ground-truth). Our results demonstrated good similarity to the ground-truth and almost identical clinical results for the prediction of SGA.