Automated multivolume placental reconstruction using three-dimensional power Doppler ultrasound and infrared camera tracking.

OBJECTIVE: Placental insufficiency contributes to many obstetric pathologies however there is no bedside clinical tool to evaluate placental perfusion. We have developed a method to acquire multiple three-dimensional power Doppler ultrasound (3D PD-US) volumes of placental vasculature with infrared camera tracking providing global coordinates. These are automatically reconstructed ('stitched') into a model of the entire placenta. The purpose of the study was to evaluate the accuracy of automated reconstruction in an US phantom and apply this technique to human placentas. METHODS: A custom-designed acrylic phantom was constructed with dimensions mimicking a third-trimester placenta, containing 12 quadrilateral towers of varying heights submersed in tissue-mimicking solution. Triplicated three-dimensional ultrasound volumes of this phantom were acquired at three different acquisition angles using infrared camera tracking. Data was transformed into a three-dimensional cartesian volume and automatically stitched. A single-centre, cross-sectional feasibility study was conducted on uncomplicated second-to-third trimester singleton pregnancies using standardised obstetric settings. Multiple 3D PD-US and grayscale volumes of the placenta were acquired with infrared camera tracked coordinates. Volumes were stitched to create a model of placental vasculature. RESULTS: 6 phantom datasets were reconstructed at each of 3 volume angles with a median of 9 volumes required. Perfect volume alignment occurred in 66.7% of 648 datapoints. Mean distance error for volume misalignment was 2.92mm. Measurements of 210 distances in each stitched volume (2160 total distances) differed an average of 1.51mm from true measurements. These compare favourably with recent literature, though for a substantially larger phantom. 17 participants were scanned with 92% reconstruction success per placental volume set and 100% participant achievability. Median reconstruction time was 10 minutes. Placental vasculature was qualitatively assessed to be present, continuous, and detailed throughout. Volume measurement of entire segmented placentas was highly repeatable (ICC 0.96). CONCLUSION: We present an automated method to model the entire structure and vasculature of second-to-third trimester placentas, with verified accuracy and clinical feasibility for grayscale and power Doppler. This study builds the foundation to develop a practical screening tool for detecting placental insufficiency, and expansion to adult organ perfusion evaluation. This article is protected by copyright. All rights reserved.

Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Screening methods for linear errors-in-variables models in high dimensions.

Microarray studies, in order to identify genes associated with an outcome of interest, usually produce noisy measurements for a large number of gene expression features from a small number of subjects. One common approach to analyzing such high-dimensional data is to use linear errors-in-variables (EIV) models; however, current methods for fitting such models are computationally expensive. In this paper, we present two efficient screening procedures, namely, corrected penalized marginal screening (PMSc) and corrected sure independence screening (SISc), to reduce the number of variables for final model building. Both screening procedures are based on fitting corrected marginal regression models relating the outcome to each contaminated covariate separately, which can be computed efficiently even with a large number of features. Under mild conditions, we show that these procedures achieve screening consistency and reduce the number of features substantially, even when the number of covariates grows exponentially with sample size. In addition, if the true covariates are weakly correlated, we show that PMSc can achieve full variable selection consistency. Through a simulation study and an analysis of gene expression data for bone mineral density of Norwegian women, we demonstrate that the two new screening procedures make estimation of linear EIV models computationally scalable in high-dimensional settings, and improve finite sample estimation and selection performance compared with estimators that do not employ a screening stage.

Assuming independence in spatial latent variable models: Consequences and implications of misspecification.

Multivariate spatial data, where multiple responses are simultaneously recorded across spatially indexed observational units, are routinely collected in a wide variety of disciplines. For example, the Southern Ocean Continuous Plankton Recorder survey collects records of zooplankton communities in the Indian sector of the Southern Ocean, with the aim of identifying and quantifying spatial patterns in biodiversity in response to environmental change. One increasingly popular method for modeling such data is spatial generalized linear latent variable models (GLLVMs), where the correlation across sites is captured by a spatial covariance function in the latent variables. However, little is known about the impact of misspecifying the latent variable correlation structure on inference of various parameters in such models. To address this gap in the literature, we investigate how misspecifying and assuming independence for the latent variables' correlation structure impacts estimation and inference in spatial GLLVMs. Through both theory and numerical studies, we show that performance of maximum likelihood estimation and inference on regression coefficients under misspecification depends on a combination of the response type, the magnitude of true regression coefficient, and the corresponding loadings, and, most importantly, whether the corresponding covariate is (also) spatially correlated. On the other hand, estimation and inference of truly nonzero loadings and prediction of latent variables is consistently not robust to misspecification of the latent variable correlation structure.

Comparative Genomic Profiling of Refractory and Metastatic Penile and Nonpenile Cutaneous Squamous Cell Carcinoma: Implications for Selection of Systemic Therapy.

PURPOSE: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma. MATERIALS AND METHODS: DNA was extracted from 40 µ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci. RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types. CONCLUSIONS: Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. TWEETABLE ABSTRACT: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

Fetal myocardial performance index in assessment and management of small-for-gestational-age fetus: a cohort and nested case-control study.

OBJECTIVE: To assess the clinical utility of the fetal myocardial performance index (MPI) in assessment and management of the small-for-gestational-age (SGA) fetus/growth-restricted fetus (FGR). METHODS: This was a prospective cohort study in metropolitan Australia of patients referred in the period June 2012 to March 2015 to fetal medicine services at 24-38 weeks' gestation for suspected singleton SGA/FGR (estimated fetal weight (EFW) < 10th centile with or without abnormal umbilical artery (UA) Doppler) pregnancy. Patients had MPI assessed in addition to routine measures, and were followed through to birth. We compared MPI values against those of a local reference population and gestational age-matched controls, and assessed the correlation with perinatal outcome and other Doppler measures. RESULTS: Fifty-two cases were included, 38 diagnosed < 32 weeks and 14 diagnosed ≥ 32 weeks. None demonstrated significantly elevated left, right or delta MPI compared with the reference population or with gestational age-matched controls at the time of first MPI evaluation. There were no consistent longitudinal patterns in MPI that would suggest its clinical utility. The mean ± SD gestational age at delivery was 34.6 ± 3.8 weeks and birth weight was 1.7 ± 0.6 kg, and the median neonatal hospital admission time was 27 days, confirming a pathological cohort. There were no significant correlations between left, right or delta-MPI and perinatal outcome, although there were significant correlations between UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler and perinatal outcome (birth weight, gestational age at birth and length of neonatal hospital stay). Exploratory subgroup comparisons (EFW < 3rd vs 3rd -10th centile; early- vs late-onset; abnormal vs normal UA Doppler) found only minor differences in MPI, reaching statistical, but not clinical, significance, only in the EFW < 3rd vs 3rd -10th centile comparison. CONCLUSIONS: MPI did not demonstrate clinical utility in either triage or longitudinal follow-up of an SGA/FGR cohort presenting to fetal medicine services. Given that prior research suggesting its utility originates from single-center cohorts, while multicenter, large cohorts have suggested little utility or no additional utility if routine UA/MCA/DV Doppler is performed, publication bias may have affected previous reports. It seems unlikely that MPI has clinical utility in assessment and management of SGA/FGR fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Beat-to-beat variability of fetal myocardial performance index.

OBJECTIVES: To determine whether there is beat-to-beat (BTB) variability in the fetal left myocardial performance index (MPI), as evaluated by an automated system, and whether there is a correlation between MPI and fetal heart rate (FHR). METHODS: This was a prospective cross-sectional study of uncomplicated, morphologically normal, singleton pregnancies at 20-38 weeks' gestation. Multiple cineloops for left MPI measurement were acquired during a single examination of each fetus. Raw cineloop data were analyzed by our automated MPI system (intraclass correlation coefficient of 1.0 for any given waveform) to produce a set of MPIs. The corresponding instantaneous FHR was measured for each individual cardiac cycle for which MPI was calculated. RESULTS: Data from 29 fetuses were analyzed; mean MPI was 0.52, mean FHR was 150 beats per min and the median number of cardiac cycles examined per fetus was 70 (interquartile range, 31-115). Marked BTB variability was noted; median coefficient of variation was 10% (range, 5.5-13.9%). FHR was weakly correlated with absolute MPI (r = 0.22; P < 0.05). BTB variation in MPI as a percentage of the mean MPI was not significantly correlated with FHR (r = 0.031; P = 0.146). When standard error of the mean of all MPI values was divided by the mean for each case, it showed that at least four cardiac cycles should be averaged to reduce MPI variability to approximately ± 5%. CONCLUSION: There is significant BTB variability in fetal left MPI, which has an overall weak correlation with FHR. This could be a factor affecting the consistency of MPI values reported by different research groups. Variability would be reduced by averaging 4-5 cardiac cycles per fetus. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Why such differing stances? A review of position statements on home birth from professional colleges.

UNLABELLED: Despite low rates of home birth throughout most Western countries, the topic generates considerable debate. This is reflected by the differing positions on home birth adopted by professional colleges representing obstetricians and midwives. We reviewed position statements of midwifery and obstetric colleges in the UK, USA, Australia, New Zealand, and Canada to explore how the same body of research evidence leads to different positions. Aside from a joint statement from the UK we found widely differing stances, reflecting traditional midwifery perspectives of birth as a physiological process versus obstetric perspectives of potential pathology. We feel the differences in position statements are largely the end product of significant confirmatory bias. TWEETABLE ABSTRACT: Review of organisational position on home birth suggests bias in literature interpretation.

Review of the correlation between blood flow velocity and polycythemia in the fetus, neonate and adult: appropriate diagnostic levels need to be determined for twin anemia-polycythemia sequence.

Twin anemia-polycythemia sequence (TAPS) is recognized increasingly antenatally by the demonstration of an anemic twin and a polycythemic cotwin using the middle cerebral artery peak systolic velocity (MCA-PSV). While the MCA-PSV has been shown to correlate well with anemia in singleton fetuses, the evidence to support its use to diagnose fetal polycythemia appears to be less clear-cut. We aimed to evaluate fetal, neonatal and adult literature used to support the use of MCA-PSV for the diagnosis of polycythemia. Comprehensive literature searches were performed for ultrasound evidence of polycythemia in the human fetus, neonate and adult using key search terms. Only manuscripts in the English language with an abstract were considered for the review, performed in June 2014. Fifteen manuscripts were found for the human fetus, including 38 cases of TAPS. Nine of these defined fetal polycythemia as MCA-PSV < 0.8 multiples of the median (MoM), five used < 1.0 MoM and one used 0.8-1.0 MoM. Only two studies, involving a total of 15 cases, proposed a diagnostic level, acknowledging false-positive and -negative cases, though neither reported sensitivities or specificities. Six neonatal studies (96 neonates) demonstrated evidence of decreased cerebral velocities in polycythemia and a consequent increase with hemodilution. In the adult, five studies (57 polycythemic adults) demonstrated increased flow or velocity with hemodilution. Neither neonatal nor adult studies conclusively defined levels for screening for polycythemia. Despite widespread adoption of a cut-off of < 0.8 MoM in the published literature for the polycythemic fetus in TAPS, this is based upon minimal evidence, with unknown sensitivity and specificity. We recommend caution in excluding TAPS based purely upon the absence of a reduced MCA-PSV.

Evaluation of an automated fetal myocardial performance index.

OBJECTIVE: To compare automated measurements of the fetal left myocardial performance index (MPI) with manual measurements for absolute value, repeatability and waveform acceptability. METHODS: This was a multicenter international online study using images from uncomplicated, morphologically normal singleton pregnancies (16-38 weeks' gestation). Single Doppler ultrasound cardiac cycle images of 25 cases were selected, triplicated and randomized (n = 75). Six senior observers, unaware of the repetition of images, manually calculated MPI for each waveform and the results were compared with automation. Intraobserver repeatability and interobserver reproducibility were assessed using intraclass correlation coefficients (ICCs) and 95% CI. The agreement between each observer's manual MPI measurements and corresponding automated measurements was evaluated using Bland-Altman plots and ICCs with 95% CI. The degree of variation between experts in the classification of fetal MPI waveform quality was assessed using individual cardiac cycle left MPI images previously classified by two authors as 'optimal', 'suboptimal' or 'unacceptable', with 30 images selected for each quality group. Ten images in each category were duplicated and the resulting 120 images were randomized and then classified online by five observers. The kappa statistic (κ) was used to demonstrate interobserver and intraobserver agreement and agreement of classifications by the five observers. RESULTS: The automated measurement software returned the same value for any given image, resulting in an ICC of 1.00. Manual measurements had intraobserver repeatability ICC values ranging from 0.69 to 0.97, and the interobserver reproducibility ICC was 0.78. Comparison of automated vs manual MPI absolute measurements for each observer gave ICCs ranging from 0.77 to 0.96. Interobserver image quality classification agreement gave k = 0.69 (P < 0.001), and the intraobserver agreement was variable (κ ranging from 0.40 to 0.81). CONCLUSIONS: Automated fetal MPI provides superior repeatability and reproducibility to manual methodology. Additionally, experts vary significantly when classifying suitability of fetal MPI waveforms. Automated MPI may facilitate clinical translation by removing human subjectivity. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Monitoring intrahepatic cholestasis of pregnancy using the fetal myocardial performance index: a cohort study.

OBJECTIVE: To investigate use of the fetal myocardial performance index (MPI) in assessing intrahepatic cholestasis of pregnancy (ICP). METHODS: This was a cohort study including cross-sectional and longitudinal data from 31 women with ICP recruited from June 2012 to March 2014. Fetal left, right and delta MPI (LMPI, RMPI and DMPI), and routine measures of fetal growth and wellbeing, were obtained at each ultrasound examination. Results were evaluated with respect to gestational age (GA)-adjusted reference intervals, level of maternal serum bile acid (SBA) and fetal outcome. Lower SBA (≥ 7.5 and < 40 µmol/L) and high SBA (≥ 40 µmol/L) subgroups of cases were defined for the analysis. RESULTS: A total of 51 ultrasound examinations were performed in 33 fetuses. The mean LMPI, and means of its isovolumetric relaxation time (IRT) and isovolumetric contraction time (ICT) components were significantly higher in all subgroups of cases of ICP relative to the normal reference mean. Considering only the first examination in each case of ICP, IRT was significantly more prolonged in the high SBA group (n = 10) in comparison to the lower SBA group (n = 23) (52.7 ± 8.0 ms vs 47.3 ± 4.8 ms, P = 0.02), and both IRT (r = 0.538, P = 0.001) and LMPI (r = 0.367, P = 0.036) were significantly correlated with SBA concentration. The proportion of high SBA cases with LMPI, RMPI or DMPI > 2 SD above the GA-adjusted reference mean was not significantly greater than for the lower SBA group. On analysis of all data from those cases with more than one examination, no significant correlation was found between SBA concentration and any of the MPI variables. CONCLUSIONS: LMPI values increase above the population GA-adjusted mean in cases of ICP, particularly amongst women with higher SBA. A significant correlation between IRT and LMPI at initial examination and increasing SBA concentration was found. A future multicenter prospective study may clarify the prognostic utility of MPI in ICP.

Randomised controlled trials and clinical maternity care: moving on from intention-to-treat and other simplistic analyses of efficacy.

BACKGROUND: The obstetrical literature is dominated by Randomised Controlled Trials (RCTs), with the vast majority being analysed using an intention-to-treat (ITT) approach. Whilst this approach may reflect well the consequence of assignment to therapy and hence the 'trialists'perspective', it may fail to address the consequence of actually receiving therapy (the patient's perspective). DISCUSSION: This review questions the ubiquitous adherence to the ITT approach, and gives examples of where this may have misled the maternity care professions. It gives an overview of techniques to overcome potential deficiencies in result presentation, using method effectiveness models such as 'Per Protocol' (PP) or 'As-Treated' (AT) that may give more accurate clinical meaning to the presentation of obstetrical results. It then proceeds to cover the added benefits, considerations and potential pitfalls of the use of Instrumental Variable (IV) models in order to better reflect the clinical context. SUMMARY: While ITT may achieve statistical purity, it frequently fails to address the true clinical or patient's perspective. Though more complex and potentially beset by problems of their own, alternative methods of result presentation may better serve the latter aim. Each of the other methods may rely on untestable assumptions and therefore it is wisest that study results are presented in multiple formats to allow for informed reader evaluation.

Pilot investigation of an activity-based approach to building hardiness.

BACKGROUND: The purpose was to describe an activity-based psychological hardiness training programme delivered by an occupational therapist and examine its acceptability and effectiveness in improving hardiness. METHOD: Participants (N=28) completed the 6-hour programme, which included pre/post-programme completion of the Dispositional Resilience Scale-15 (DRS-15) and a Program Evaluation Form. Paired t-tests were used to determine differences between pre-training and post-training scores on the DRS-15. RESULTS: Results showed a significant increase (p<0.05) in total hardiness, commitment, and control scores on the DRS-15 from pre-training to post-training and good-excellent ratings for all categories on the Program Evaluation Form. CONCLUSIONS: This programme evaluation described an occupational therapist's role in providing an activity-based psychological hardiness training programme and provided preliminary support for the acceptability of an activity-based approach to training psychological hardiness for service members.

Fetal left modified myocardial performance index: technical refinements in obtaining pulsed-Doppler waveforms.

OBJECTIVE: To assess the influence of machine settings (wall motion filter (WMF), angle of insonation, Doppler aliasing) and phase of valve clicks on repeatability of measurement of the fetal left modified myocardial performance index (Mod-MPI). METHODS: Fetal left Mod-MPI was evaluated prospectively in 157 morphologically normal fetuses at 19-36 weeks' gestation. In a baseline cohort, a previously published technique and settings were used for measurement of Mod-MPI. In a second cohort, the influence of WMF, angle of insonation, Doppler aliasing and selection of the phase of the valve clicks on repeatability of measurement of Mod-MPI was assessed. RESULTS: The intraclass correlation coefficient (ICC) for measurement repeatability in the baseline cohort was 0.22. Increase in WMF to 300 Hz or 500 Hz was associated with an increase in ICC to 0.60 and 0.55, respectively. An angle of insonation of < 15° was associated with an increase in ICC to 0.79 and 0.78 at a WMF of 300 and 500 Hz, respectively. A WMF of 300 Hz, angle of insonation of < 15° and absence of aliasing was associated with an increase in ICC to 0.85 and 0.87 at the beginning and peak of the valve click, respectively. Mod-MPI ranged from 0.35 to 0.48. An increase in calculated MPI was associated with increasing WMF, selection of the beginning vs. peak of the valve clicks and increase in angle of insonation. The presence or absence of aliasing had no effect. CONCLUSIONS: Refinement of machine settings improves repeatability of Mod-MPI, as does selection of the peak of the valve click. We suggest a consensus be reached as to the precise measurement of MPI, but for the moment would suggest: WMF, 300 Hz; angle of insonation, < 15°; avoiding Doppler aliasing; and selection of valve click peak. Systematic variation in measurement of time intervals may be responsible for the widely varying published normal ranges for Mod-MPI.

Reproducibility of constituent time intervals of right and left fetal modified myocardial performance indices on pulsed Doppler echocardiography: a short report.

OBJECTIVE: To assess reproducibility of constituent time intervals measured by pulsed Doppler echocardiography for calculation of the right and left fetal myocardial performance indices (MPIs). METHODS: This was a prospective study of 30 normal singleton pregnancies (19-36 weeks). In each, five different time intervals were measured from the Doppler waveform and four repeated measures were taken for each time interval. Three were from the left heart: isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT) and ejection time (ET); two were from the right heart: 'a-interval' and 'b-interval'. The left and right modified MPIs (Mod-MPIs) generated by these constituent time intervals were also evaluated. Two operators evaluated the reproducibility of all measures. RESULTS: There was generally good intra- and interobserver reproducibility for all time intervals and resultant Mod-MPIs: ICT, range, 19-43 ms with intraclass correlation coefficient (ICC), 0.91 (95% CI, 0.85-0.95); ET, range, 160-184.8 ms with ICC, 0.90 (95% CI, 0.84-0.95); IRT, range, 35.8-48.5 ms with ICC, 0.67 (95% CI, 0.52-0.81); a-interval, range 208-265 ms with ICC, 0.89 (95% CI, 0.82-0.94); b-interval, range, 163.1-188.3 ms with ICC, 0.82 (95% CI, 0.71-0.90); left Mod-MPI, range, 0.33-0.48 with ICC, 0.84 (95% CI, 0.74-0.91); right Mod-MPI, range, 0.21-0.49 with ICC, 0.82 (95% CI, 0.71-0.90). The 95% limits of agreement showed no statistically significant difference in measurements between the two examiners for all time intervals. CONCLUSION: This is the first study to evaluate the reproducibility of the component time intervals of both right and left fetal Mod-MPIs in the second and third trimesters and supports the reproducibility of fetal functional cardiac assessment. The IRT is the main source of variation for the left Mod-MPI so should be the focus of further investigation. Even using two separate pulsed-wave Doppler gates and therefore separate cardiac cycles, the right Mod-MPI is reproducible.

Spatiotemporal image correlation-derived volumetric Doppler impedance indices from spherical samples of the placenta: intraobserver reliability and correlation with conventional umbilical artery Doppler indices.

OBJECTIVE: Volumetric impedance indices derived from spatiotemporal image correlation (STIC) power Doppler ultrasound (PDU) might overcome the influence of machine settings and attenuation. We examined the feasibility of obtaining these indices from spherical samples of anterior placentas in healthy pregnancies, and assessed intraobserver reliability and correlation with conventional umbilical artery (UA) impedance indices. METHODS: Uncomplicated singleton pregnancies with anterior placenta were included in the study. A single observer evaluated UA pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D) and acquired three STIC-PDU datasets from the placenta just above the placental cord insertion. Another observer analyzed the STIC-PDU datasets using Virtual Organ Computer-aided AnaLysis (VOCAL) spherical samples from every frame to determine the vascularization index (VI) and vascularization flow index (VFI); maximum, minimum and average values were used to determine the three volumetric impedance indices (vPI, vRI, vS/D). Intraobserver reliability was examined by intraclass correlation coefficients (ICC) and association between volumetric indices from placenta, and UA Doppler indices were assessed by Pearson's correlation coefficient. RESULTS: A total of 25 pregnant women were evaluated but five were excluded because of artifacts observed during analysis. The reliability of measurement of volumetric indices of both VI and VFI from three STIC-PDU datasets was similar, with all ICCs ≥ 0.78. Pearson's r values showed a weak and non-significant correlation between UA pulsed-wave Doppler indices and their respective volumetric indices from spherical samples of placenta (all r ≥ 0.23). VOCAL indices from specific phases of the cardiac cycle showed good repeatability (ICC ≥ 0.92). CONCLUSION: Volumetric impedance indices determined from spherical samples of placenta are sufficiently reliable but do not correlate with UA Doppler indices in healthy pregnancies.

Influence of power Doppler gain setting on Virtual Organ Computer-aided AnaLysis indices in vivo: can use of the individual sub-noise gain level optimize information?

OBJECTIVES: To demonstrate the influence of gain setting on the calculated Virtual Organ Computer-aided AnaLysis (VOCAL(™)) three-dimensional (3D) indices and define a point, the sub-noise gain (SNG), at which maximum information is available without noise artifact. METHODS: Pregnant women were recruited at the time of their pregnancy-dating scan. Five identical static 3D power Doppler volumes of the placenta were acquired using identical machine settings apart from altering the power Doppler gain setting. The gain settings included the individualized SNG setting (determined by increasing gain until noise artifact was visible, then reducing it until the artifact just disappeared). The data were analyzed using VOCAL II. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated for the same sample at five different power Doppler gain levels. The relationship between the values calculated for the VOCAL indices and the gain value was explored using linear regression analysis. RESULTS: Results from 50 women were analyzed. The percentage difference in VI and VFI from that observed at the SNG level in each woman was significantly linearly related to the gain setting relative to that at the SNG point (VI: r(2) = 0.68, P < 0.0001; VFI: r(2) = 0.72, P < 0.0001), with the values produced for VI and VFI decreasing as the gain was turned down. There was a distinct 'turning point' at the SNG level with linear relationships above and below, but with significantly different gradients (P ≤ 0.001). This relationship was not demonstrated for FI. CONCLUSION: The SNG setting appears to represent each individual's optimum gain level. Using this may improve meaningful comparisons of VI and VFI between patients.

Inapplicability of fractional moving blood volume technique to standardize Virtual Organ Computer-aided AnaLysis indices for quantified three-dimensional power Doppler.

OBJECTIVE: To determine whether the technique of fractional moving blood volume (FMBV) is applicable to Virtual Organ Computer-aided AnaLysis II (VOCAL II™)-based indices to quantify three-dimensional power Doppler ultrasound (3D-PDU) by investigating the effect of gain level on the indices measured at a possible reference point for standardization. METHODS: Ten women with singleton pregnancy between 33+3 and 37+5 weeks' gestation were recruited. The optimal position for 3D acquisition of cord insertion into the placenta was identified and static 3D-PDU volumes were acquired using consistent machine configurations. Without moving the probe or the participant changing position, successive 3D volumes were stored at -3, -5, -7 and -9 dB and at the individualized sub-noise gain (SNG) level. Volumes were excluded if flash artifact was present, in which case all five volumes were reacquired. Using 4D View software, the cord insertion was magnified and the smallest sphere possible was used to measure vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The associations between VOCAL indices and gain level were assessed using Pearson's correlation coefficient. RESULTS: VOCAL indices for cord insertion correlated poorly with gain level, whether fundamental or relative to SNG level (R(2) = 0.07 and 0.04, respectively). VI was consistently 100% and mean FI and VFI were 99.5 (SD, 0.57), with all values > 97 irrespective of gain level. CONCLUSIONS: Whilst previous work has shown that gain correlates well with placental tissue VOCAL indices, the correlation between gain level and VOCAL indices in an area of 100% vascularity at the cord insertion is poor. Regions of 100% vascularity appear to be artificially assigned a value approaching 100% for all VOCAL indices irrespective of gain level. This precludes using the technique of VOCAL indices from large vessels to standardize power Doppler measurements and the FMBV index is therefore not applicable to image analysis using VOCAL.

Three-dimensional Doppler evaluation of single spherical samples from the placenta: intra- and interobserver reliability.

OBJECTIVE: To evaluate the intra- and interobserver reliability of assessment of three-dimensional power Doppler (3D-PD) indices from single spherical samples of the placenta. METHODS: Women with singleton pregnancies at 24-40 weeks' gestation were included. Three scans were independently performed by two observers; Observer 1 performed the first and third scan, intercalated by the scan of Observer 2. The observers independently analyzed the 3D-PD datasets that they had previously acquired using four different methods, each using a spherical sample: random sample extending from basal to chorionic plate; random sample with 2 cm(3) of volume; directed sample to the region subjectively determined as containing more color Doppler signals extending from basal to chorionic plate; or directed sample with 2 cm(3) of volume. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were evaluated in each case. The observers were blinded to their own and each other's results. Additional evaluation was performed according to placental location: anterior, posterior and fundal or lateral. Intra- and interobserver reliability was assessed by intraclass correlation coefficients (ICC). RESULTS: Ninety-five pregnancies were included in the analysis. All three placental 3D-PD indices showed only weak to moderate reliability (ICC < 0.66 and ICC < 0.48, intra- and interobserver, respectively). The highest values of ICC were observed when using directed spherical samples from basal to chorionic plate. When analyzed by placental location, we found lower ICCs for lateral and fundal placentae compared to anterior and posterior ones. CONCLUSION: Intra- and interobserver reliability of assessment of placental 3D-PD indices from single spherical samples in pregnant women greater than 24 weeks' gestation is poor to moderate, and clinical usefulness of these indices is likely to be limited.