Maternal serum PlGF associates with 3D power doppler ultrasound markers of utero-placental vascular development in the first trimester: the rotterdam periconception cohort.

OBJECTIVE (S): Circulating angiogenic factors are used for prediction of placenta-related complications, but their associations with first-trimester placental development is unknown. This study investigates associations between maternal angiogenic factors and utero-placental vascular volume (uPVV) and utero-placental vascular skeleton (uPVS) as novel imaging markers of volumetric and morphologic (branching) development of the first-trimester utero-placental vasculature. METHODS: In 185 ongoing pregnancies from the VIRTUAL Placenta study, a subcohort of the ongoing prospective Rotterdam Periconception cohort, three-dimensional power Doppler ultrasounds of the placenta were obtained at 7-9-11 weeks gestational age (GA). The uPVV was measured as a parameter of volumetric development and reported the vascular quantity in cm3. The uPVS was generated as a parameter of morphologic (branching) development and reported the number of end-, bifurcation- crossing- or vessel points and total vascular length. At 11 weeks GA, maternal serum biomarkers suggested to reflect placental (vascular) development were assessed: placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). sFlt-1/PlGF and sEng/PlGF ratios were calculated. Multivariable linear regression with adjustments was used to estimate associations between serum biomarkers and uPVV and uPVS trajectories. RESULTS: Serum PlGF was positively associated with uPVV and uPVS development (uPVV: ß = 0.39, 95% CI = 0.15;0.64; bifurcation points: ß = 4.64, 95% CI = 0.04;9.25; crossing points: ß = 4.01, 95% CI = 0.65;7.37; total vascular length: ß = 13.33, 95% CI = 3.09;23.58, all p-values < 0.05). sEng/PlGF ratio was negatively associated with uPVV and uPVS development. We observed no associations between sFlt-1, sEng or sFlt-1/PlGF ratio and uPVV and uPVS development. CONCLUSION(S): Higher first-trimester maternal serum PlGF concentration is associated with increased first-trimester utero-placental vascular development as reflected by uPVV and uPVS. Clinical trial registration number Dutch Trial Register NTR6854.

Assessment of first-trimester utero-placental vascular morphology by 3D power Doppler ultrasound image analysis using a skeletonization algorithm: the Rotterdam Periconception Cohort.

STUDY QUESTION: Can three-dimensional (3D) Power Doppler (PD) ultrasound and a skeletonization algorithm be used to assess first-trimester development of the utero-placental vascular morphology? SUMMARY ANSWER: The application of 3D PD ultrasonography and a skeletonization algorithm facilitates morphologic assessment of utero-placental vascular development in the first trimester and reveals less advanced vascular morphologic development in pregnancies with placenta-related complications than in pregnancies without placenta-related complications. WHAT IS KNOWN ALREADY: Suboptimal development of the utero-placental vasculature is one of the main contributors to the periconceptional origin of placenta-related complications. The nature and attribution of aberrant vascular structure and branching patterns remain unclear, as validated markers monitoring first-trimester utero-placental vascular morphologic development are lacking. STUDY DESIGN, SIZE, DURATION: In this prospective observational cohort, 214 ongoing pregnancies were included before 10 weeks gestational age (GA) at a tertiary hospital between January 2017 and July 2018, as a subcohort of the ongoing Rotterdam Periconception Cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: By combining 3D PD ultrasonography and virtual reality, utero-placental vascular volume (uPVV) measurements were obtained at 7, 9 and 11 weeks GA. A skeletonization algorithm was applied to the uPVV measurements to generate the utero-placental vascular skeleton (uPVS), a network-like structure containing morphologic characteristics of the vasculature. Quantification of vascular morphology was performed by assigning a morphologic characteristic to each voxel in the uPVS (end-, vessel-, bifurcation- or crossing-point) and calculating total vascular network length. A Mann-Whitney U test was performed to investigate differences in morphologic development of the first-trimester utero-placental vasculature between pregnancies with and without placenta-related complications. Linear mixed models were used to estimate trajectories of the morphologic characteristics in the first trimester. MAIN RESULTS AND THE ROLE OF CHANCE: All morphologic characteristics of the utero-placental vasculature increased significantly in the first trimester (P < 0.005). In pregnancies with placenta-related complications (n = 54), utero-placental vascular branching was significantly less advanced at 9 weeks GA (vessel points P = 0.040, bifurcation points P = 0.050, crossing points P = 0.020, total network length P = 0.023). Morphologic growth trajectories remained similar after adjustment for parity, conception mode, foetal sex and occurrence of placenta-related complications. LIMITATIONS, REASONS FOR CAUTION: The tertiary setting of this prospective observational study provides high internal, but possibly limited external, validity. Extrapolation of the study's findings should therefore be addressed with caution. WIDER IMPLICATIONS OF THE FINDINGS: The uPVS enables assessment of morphologic development of the first-trimester utero-placental vasculature. Further investigation of this innovative methodology needs to determine its added value for the assessment of (patho-) physiological utero-placental vascular development. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered at the Dutch Trial Register (NTR6854).

Innovative approach for first-trimester fetal organ volume measurements using a Virtual Reality system: The Generation R Next Study.

INTRODUCTION: To investigate the reproducibility of first-trimester fetal organ volume measurements using three-dimensional (3D) ultrasound and a Virtual Reality system. METHODS: Within a population-based prospective cohort study, 3D ultrasound datasets of 25 first-trimester fetuses were collected by three sonographers. We used the V-scope application to perform Virtual Reality volume assessments of the fetal heart, lungs, and kidneys. All measurements were performed by two independent researchers. RESULTS: Intraobserver analyses for volume measurements of the fetal heart, lungs, and kidneys showed intraclass correlation coefficients ≥0.86, mean differences ≤8.3%, and coefficients of variation ≤22.8%. Interobserver analyses showed sufficient agreement for right lung volume measurements, but consistent measurement differences between observers for left lung, heart, and kidney volume measurements (p-values <0.05). CONCLUSION: We observed sufficient intraobserver reproducibility, but overall suboptimal interobserver reproducibility for first-trimester fetal heart, lung, and kidney volume measurements using an innovative Virtual Reality approach. In the current stage, these measurements might be promising for the use in research settings. The reproducibility of the measurements might be further improved by novel post-processing algorithms.

Corpus luteum number and the maternal renin-angiotensin-aldosterone system as determinants of utero-placental (vascular) development: the Rotterdam Periconceptional Cohort.

BACKGROUND: Pregnancies with > 1 corpus luteum (CL) display a hyperdynamic circulation and an increased risk of small-for-gestational age deliveries. Among the factors released by the CL is prorenin, the inactive precursor of renin. Since the renin-angiotensin-aldosterone system (RAAS) is involved in early hemodynamic pregnancy adaptation, we linked both CL number and first-trimester concentrations of prorenin (as an indicator of RAAS activity) and the aldosterone/renin ratio (as an indicator of angiotensin-independent aldosterone effectiveness) to non-invasive markers of utero-placental (vascular) development, measured longitudinally from the first trimester onwards. METHODS: A total of 201 women, who conceived naturally or after in-vitro fertilization treatment (with 0 (n = 8), 1 (n = 143), or > 1 (n = 51) CL), were selected from the Rotterdam Periconceptional Cohort. Maternal RAAS components were determined at 11 weeks gestation. Placental volume and utero-placental vascular volume were measured from transvaginal 3D ultrasound scans at 7, 9 and 11 weeks gestation, pulsatility and resistance indices of the uterine arteries were assessed by pulsed wave Doppler ultrasounds at 7, 9, 11, 13, 22 and 32 weeks gestation. At birth placental weight was obtained using standardized procedures. RESULTS: Pregnancies without a CL show lower uterine artery indices throughout gestation than 1 CL and > 1 CL pregnancies, while parameters of placental development are comparable among the CL groups. After adjustment for patient- and treatment-related factors, first-trimester prorenin concentrations are positively associated with uterine artery pulsatility and resistance indices (ß 0.06, 95% CI 0.01;0.12, p = 0.04 and ß 0.10, 95% CI 0.01;0.20, p = 0.04, respectively), while high prorenin concentrations are negatively associated with first-trimester utero-placental vascular volume (ß -0.23, 95% CI -0.44;-0.02, p = 0.04) and placental weight (ß -93.8, 95%CI -160.3;-27.4, p = 0.006). In contrast, the aldosterone/renin ratio is positively associated with first-trimester placental volume (ß 0.12, 95% CI 0.01;0.24, p = 0.04). CONCLUSIONS: The absence of a CL, resulting in low prorenin concentrations, associates with low uterine artery pulsatility and resistance, while high prorenin concentrations associate with a low utero-placental vascular volume and weight. These data support a scenario in which excess prorenin, by upregulating angiotensin II, increases uterine resistance, thereby preventing normal placental (vascular) development, and increasing the risk of small-for-gestational age deliveries. Simultaneously, high aldosterone concentrations, by ensuring volume expansion, exert the opposite.

First trimester fetal proportion volumetric measurements using a Virtual Reality approach.

OBJECTIVE: To establish feasibility and reproducibility of fetal proportion volumetric measurements, using three-dimensional (3D) ultrasound and a Virtual Reality (VR) system. METHODS: Within a population-based prospective birth cohort, 3D ultrasound datasets of 50 fetuses in the late first trimester were collected by three ultrasonographers in a single research center. V-scope software was used for volumetric measurements of total fetus, extremities, head-trunk, head, trunk, thorax, and abdomen. All measurements were performed independently by two researchers. Intraobserver and interobserver reproducibility were analyzed using Bland and Altman methods. RESULTS: Intraobserver and interobserver analyses of volumetric measurements of total fetus, head-trunk, head, trunk, thorax and abdomen showed intraclass correlation coefficients above 0.979, coefficients of variation below 7.51% and mean difference below 3.44%. The interobserver limits of agreement were within the ±10% range for volumetric measurements of total fetus, head-trunk, head and trunk. The interobserver limits of agreement for extremities, thorax and abdomen were -26.09% to 4.77%, -14.14% to 10.00% and -14.47% to 8.83%, respectively. CONCLUSION: First trimester fetal proportion volumetric measurements using 3D ultrasound and VR are feasible and reproducible, except volumetric measurements of the fetal extremities. These novel volumetric measurements may be used in future research to enable detailed studies on first trimester fetal development and growth.

Evaluation of embryonic posture using four-dimensional ultrasound and virtual reality.

AIM: To assess the possibility of embryonic posture evaluation (=feasibility, reproducibility, variation) at rest at 9 weeks' (+0-6 days) gestational age (GA) using four-dimensional ultrasound and virtual reality (VR) techniques. Moreover, it is hypothesized that embryonic posture shows variation at the same time point in an uneventful pregnancy. METHODS: In this explorative prospective cohort study, 23 pregnant women were recruited from the Rotterdam periconceptional cohort. A transvaginal four-dimensional ultrasound examination of 30 min per pregnancy was performed between 9 and 10 weeks' GA. The acquired datasets were offline evaluated longitudinally (i.e. per frame) using VR techniques. RESULTS: The ultrasound data of 16 (70%) out of 23 pregnancies were eligible for evaluation. At rest the analysis of the embryonic posture was feasible and showed a strong (>80%) intraobserver and interobserver reproducibility for most body parts. The majority of the body parts were in similar anatomic positions at rest. However, variations in anatomic positions (e.g. 6% rotated head, 9% laterally bent spine), within and between embryos, were seen at 9 weeks' GA. CONCLUSION: In this unique study, we showed for the first time that embryonic posture measurements at rest can be performed in a reliable way using state-of-the-art four-dimensional ultrasound and VR techniques. Already early in prenatal life there are differences regarding posture within and between embryos.

Effect of human embryonic morphological development on fetal growth parameters: the Rotterdam Periconceptional Cohort (Predict Study).

RESEARCH QUESTION: Is embryonic morphological development according to the Carnegie stages associated with pregnancy outcome? DESIGN: In a tertiary hospital-based cohort, 182 singleton non-malformed pregnancies were selected. Serial transvaginal three-dimensional ultrasound (3D-US) scans were carried out between 6+0 and 10+2 gestational weeks. Embryonic development was annotated according to the morphological criteria of the Carnegie classification using a virtual reality system. Second-trimester biparietal diameter, head circumference, abdominal circumference and femur length measurements were retrieved from medical records. Z-scores were calculated for mid-pregnancy estimated fetal weight (EFW) and newborn birth weight. Associations between longitudinal Carnegie stages and fetal growth parameters were investigated using linear mixed models, with subgroup analysis based on fetal gender. RESULTS: A total of 576 first-trimester 3D-US scans were analysed (median of three scans per pregnancy). Embryonic development was positively associated with EFW z-score (ß = 0.69; 95% CI 0.51 to 0.86; P < 0.001), biparietal diameter and femur length, but not with head circumference, abdominal circumference and birth weight z-score. After stratification for fetal gender, positive associations for both males and females were confirmed between embryonic development and EFW z-scores. Moreover, opposite gender-specific associations were detected between embryonic development and birth weight z-scores (males: ß = 0.37; 95% CI 0.04 to 0.70; P < 0.05; females: ß = -0.36; 95% CI -0.62 to -0.10; P < 0.01). CONCLUSIONS: Human embryonic development according to the Carnegie stages is associated with fetal growth parameters with gender-specificity of birth weight. These results emphasize the importance of the first-trimester of pregnancy, raising the morphological staging of the embryo as a new methodology for early risk assessment and improvement of subsequent fetal growth parameters.

First trimester physiological development of the fetal foot position using three-dimensional ultrasound in virtual reality.

AIM: In anatomic studies of the embryo, it has been established that during the development of the lower limb, several changes in foot position can be observed defined as a temporary 'physiological clubfoot'. The aim of this study was to develop and test a measurement tool for objective documentation of the first trimester foot position in vivo and made an attempt to create a chart for first trimester foot position. METHODS: We developed a virtual orthopedic protractor for measuring foot positioning using three-dimensional virtual reality visualization. Three-dimensional ultrasound volumes of 112 pregnancies of women examined during the first trimester were studied in a BARCO I-Space. The frontal angle (plantar flexion) and the lateral angle (adduction) between the leg and foot were measured from 8 until 13 weeks gestational age. RESULTS: We observed that the frontal angle steadily decreases, whereas the lateral angle first increases, resulting in transient physiological clubfeet position at 10- to 11-week gestation, followed by a decrease to a normal foot position. CONCLUSION: A transient clubfoot position is present during the normal development of the lower limbs, and it has been measured in vivo for the first time. This study emphasizes that a diagnosis of congenital clubfoot should not be made in the first trimester of pregnancy.

Evaluation of First-Trimester Physiological Midgut Herniation Using Three-Dimensional Ultrasound.

INTRODUCTION: The aim of this study was to investigate the development of midgut herniation in vivo using three-dimensional (3D) ultrasonographic volume and distance measurements and to create reference data for physiological midgut herniation in ongoing pregnancies in a tertiary hospital population. MATERIALS AND METHODS: The transvaginal 3D ultrasound volumes of 112 women, seen weekly during the first trimester of pregnancy, were obtained and subsequently analysed in a virtual reality environment. The width of the umbilical cord insertion, the maximum diameter of the umbilical cord, and the volume of midgut herniation were measured from 6 until 13 weeks gestational age (GA). RESULTS: All parameters had a positive relation with GA, crown-rump length, and abdominal circumference. In approximately 1 of 10 volumes no midgut herniation could be observed at 9 and 10 weeks GA. In 5.0% of the fetuses the presence of midgut herniation could still be visualised at 12 weeks GA. CONCLUSION: Reference charts for several dimensions of physiological midgut herniation were created. In the future, our data might be used as a reference in the first trimester for comparison in case of a suspected pathological omphalocele.

Accuracy of fetal sex determination in the first trimester of pregnancy using 3D virtual reality ultrasound.

PURPOSE: Early detection of fetal sex is becoming more popular. The aim of this study was to evaluate the accuracy of fetal sex determination in the first trimester, using 3D virtual reality. METHODS: Three-dimensional (3D) US volumes were obtained in 112 pregnancies between 9 and 13 weeks of gestational age. They were offline projected as a hologram in the BARCO I-Space and subsequently the genital tubercle angle was measured. Separately, the 3D US aspect of the genitalia was examined for having a male or female appearance. RESULTS: Although a significant difference in genital tubercle angles was found between male and female fetuses, it did not result in a reliable prediction of fetal gender. Correct sex prediction based on first trimester genital appearance was at best 56%. CONCLUSION: Our results indicate that accurate determination of the fetal sex in the first trimester of pregnancy is not possible, even using an advanced 3D US technique.

Preoperative prediction of cosmetic results in breast conserving surgery.

BACKGROUND: Preoperative objective predictions of cosmetic result after breast conserving surgery (BCS) has the potential to aid in surgical treatment decision making. Our aim was to investigate the predictive value of tumor volume in relation to breast volume (TV/BV ratio) for cosmetic result. METHODS: Sixty-nine invasive breast cancer women with preoperative MRI and treated by BCS and radiotherapy in 2007-2012 were prospectively included. Simple excision or basic oncoplastic techniques were used, but no volume displacement. TV/BV ratio was measured in the MRI while 3D-projected in virtual reality environment (I-Space). Cosmetic result was assessed by patient questionnaire, panel evaluation, and breast retraction assessment (BRA). Quality-of-life was assessed by EORTC QLQ-C30 and BR23. RESULTS: Intraobserver and interobserver correlation coefficients for tumor and breast volume were all >0.95. Increasing TV/BV ratio correlated with decreasing cosmetic result as determined by patient, panel, and BRA. TV/BV ratio was a significant independent predictor for the panel evaluation (P=0.028), as was tumor location (P<0.05), and together they constituted a good prediction model (AUC 0.83). CONCLUSIONS: TV/BV ratio was a precise and independent predictor for cosmetic result determined by a panel and can be used as preoperative prediction tool to enable more informed surgical treatment decision making.

Design and validation of a 3D virtual reality desktop system for sonographic length and volume measurements in early pregnancy evaluation.

PURPOSE: To design and validate a desktop virtual reality (VR) system, for presentation and assessment of volumetric data, based on commercially off-the-shelf hardware as an alternative to a fully immersive CAVE-like I-Space VR system. METHODS: We designed a desktop VR system, using a three-dimensional (3D) monitor and a six degrees-of-freedom tracking system. A personal computer uses the V-Scope (Erasmus MC, Rotterdam, The Netherlands) volume-rendering application, developed for the I-Space, to create a hologram of volumetric data. Inter- and intraobserver reliability for crown-rump length and embryonic volume measurements are investigated using Bland-Altman plots and intraclass correlation coefficients. Time required for the measurements was recorded. RESULTS: Comparing the I-Space and the desktop VR system, the mean difference for crown-rump length is -0.34% (limits of agreement -2.58-1.89, ±2.24%) and for embryonic volume -0.92% (limits of agreement -6.97-5.13, ±6.05%). Intra- and interobserver intraclass correlation coefficients of the desktop VR system were all >0.99. Measurement times were longer on the desktop VR system compared with the I-Space, but the differences were not statistically significant. CONCLUSIONS: A user-friendly desktop VR system can be put together using commercially off-the-shelf hardware at an acceptable price. This system provides a valid and reliable method for embryonic length and volume measurements and can be used in clinical practice.

First-trimester hand measurements in euploid and aneuploid human fetuses using virtual reality.

OBJECTIVE: Although second-trimester and third-trimester reference curves for human fetal hand growth allow for identification of several genetic syndromes, little is known about first-trimester hand growth. We investigated first-trimester hand growth in euploid and aneuploid fetuses. METHOD: Between 9 and 12 weeks' gestational age (GA), wrist width, hand width, hand length, and hand index were measured in three-dimensional (3D) ultrasound datasets of 112 euploid and 65 aneuploid pregnancies. We constructed reference curves for these measurements in euploid pregnancies and calculated z-scores for measurements in aneuploid pregnancies. Reproducibility was established in a subset of 20 datasets. RESULTS: While wrist width, hand width, and hand length increased with gestational age, hand index decreased. Intraobserver and interobserver intraclass correlation coefficient values were >0.97. In trisomy 21 cases, wider wrists and hands were observed compared with euploid pregnancies (mean z-scores 1.06, SD 2.04, p < 0.001 and 1.16, SD 1.30, p < 0.001, respectively). Trisomy 18 cases showed narrower and shorter hands (mean z-scores -0.74, SD 1.20, p = 0.009 and -0.97, SD 0.86, p = 0.005, respectively). In trisomy 13 cases, no differences were observed. CONCLUSION: Reference values are available for first-trimester studies on human hand development. First-trimester hand measurements in trisomies 21 and 18 differ significantly from those in euploid pregnancies and may be useful for early identification of abnormal development.

First-trimester 3D power Doppler imaging markers of utero-placental vascular development are associated with placental weight and diameter at birth: The Rotterdam Periconception Cohort.

INTRODUCTION: Early utero-placental vascular development impacts placental development and function throughout pregnancy. We investigated whether impaired first-trimester utero-placental vascular development is associated with pathologic features of the postpartum placenta. METHODS: In this prospective observational study of 65 ongoing pregnancies, we obtained three-dimensional power Doppler ultrasounds of the placenta at 7, 9 and 11 weeks of gestation. We applied VOCAL software to measure placental volume (PV), virtual reality based segmentation to measure utero-placental vascular volume (uPVV) and applied a skeletonization algorithm to generate the utero-placental vascular skeleton (uPVS). Vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-, crossing- or vessel point). Following delivery, placentas were measured and histologically examined according to the Amsterdam criteria to assess maternal vascular malperfusion (MVM). We used linear mixed models to estimate trajectories of PV, uPVV and uPVS development. Multivariable linear regression analysis with adjustments for confounders was used to evaluate associations between PV, uPVV and uPVS development and features of the postpartum placenta. RESULTS: We observed no associations between first-trimester PV development and measurements of the postpartum placenta. Increased first-trimester utero-placental vascular development, reflected by uPVV (ß = 0.25 [0.01; 0.48]), uPVS end points (ß = 0.25 [0.01; 0.48]), bifurcation points (ß = 0.22 [0.05; 0.37]), crossing points (ß = 0.29 [0.07; 0.52]) and vessel points (ß = 0.09 [0.02; 0.17]) was positively associated with the postpartum placental diameter. uPVV was positively associated with postpartum placental weight. No associations were found with MVM. DISCUSSION: Development of the first-trimester utero-placental vasculature is associated with postpartum placental size, whereas placental tissue development contributes to a lesser extent.

Human embryonic growth trajectories and associations with fetal growth and birthweight.

STUDY QUESTION: How do human embryonic growth trajectories evolve in the first trimester, and is first-trimester embryonic growth associated with fetal growth and birthweight (BW)? SUMMARY ANSWER: Human embryonic growth rates increase between 9 and 10 weeks of gestation and are associated with mid-pregnancy fetal growth and BW. WHAT IS KNOWN ALREADY: Fetal growth is associated with health and disease risks in later life. Until recently, prenatal care and research have been focused predominantly on fetal growth in the second and third trimesters of pregnancy. Longitudinal first-trimester data remain scarce. STUDY DESIGN, SIZE, DURATION: We recruited 201 pregnancies before 8 weeks of gestation in a prospective periconception cohort study conducted in a tertiary center. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed weekly 3D ultrasound scans from enrollment up to 13 weeks of gestation. To create embryonic growth trajectories, serial crown-rump length (CRL) measurements were performed using the V-Scope software in the BARCO I-Space. Mid-pregnancy fetal growth parameters and BW were obtained from medical records. Z-scores were calculated for CRL, mid-pregnancy estimated fetal weight (EFW) and BW. Associations between embryonic and fetal growth parameters were investigated using Pearson's correlation coefficients. MAIN RESULTS AND THE ROLE OF CHANCE: During the early first trimester (up to 9 weeks of gestation), we observed a constant absolute mean embryonic CRL growth rate of 0.99 mm/day (SD 0.10), while the relative growth rate decreased. Between 9 and 10 weeks of gestation, the absolute growth rate increased, and during late first trimester (from 10 weeks of gestation onward), we observed a constant mean relative growth rate of 4.1% (SD 0.006) per day. Overall, early and late first-trimester median CRL Z-scores were strongly correlated with mid-pregnancy EFW (r overall/early/late = 0.57/0.57/0.54, P < 0.001) but only overall and late CRL Z-scores were correlated with BW (r overall = 0.15, P = 0.04; r early = 0.10, P = 0.17; r late = 0.17, P = 0.02). LIMITATIONS, REASONS FOR CAUTION: This study was conducted in a tertiary hospital. Therefore, future studies in other populations are warranted to confirm our results. WIDER IMPLICATIONS OF THE FINDINGS: This study shows differences between early and late first-trimester embryonic growth coinciding with changes in intrauterine nourishment. The established associations between first-trimester embryonic growth and fetal size in mid-pregnancy and at birth emphasize that more research is warranted to establish the importance of these results for preconceptional and early pregnancy care.

Computational methods for the analysis of early-pregnancy brain ultrasonography: a systematic review.

BACKGROUND: Early screening of the brain is becoming routine clinical practice. Currently, this screening is performed by manual measurements and visual analysis, which is time-consuming and prone to errors. Computational methods may support this screening. Hence, the aim of this systematic review is to gain insight into future research directions needed to bring automated early-pregnancy ultrasound analysis of the human brain to clinical practice. METHODS: We searched PubMed (Medline ALL Ovid), EMBASE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar, from inception until June 2022. This study is registered in PROSPERO at CRD42020189888. Studies about computational methods for the analysis of human brain ultrasonography acquired before the 20th week of pregnancy were included. The key reported attributes were: level of automation, learning-based or not, the usage of clinical routine data depicting normal and abnormal brain development, public sharing of program source code and data, and analysis of the confounding factors. FINDINGS: Our search identified 2575 studies, of which 55 were included. 76% used an automatic method, 62% a learning-based method, 45% used clinical routine data and in addition, for 13% the data depicted abnormal development. None of the studies shared publicly the program source code and only two studies shared the data. Finally, 35% did not analyse the influence of confounding factors. INTERPRETATION: Our review showed an interest in automatic, learning-based methods. To bring these methods to clinical practice we recommend that studies: use routine clinical data depicting both normal and abnormal development, make their dataset and program source code publicly available, and be attentive to the influence of confounding factors. Introduction of automated computational methods for early-pregnancy brain ultrasonography will save valuable time during screening, and ultimately lead to better detection, treatment and prevention of neuro-developmental disorders. FUNDING: The Erasmus MC Medical Research Advisor Committee (grant number: FB 379283).

Visualization of postoperative anterior cruciate ligament reconstruction bone tunnels: reliability of standard radiographs, CT scans, and 3D virtual reality images.

BACKGROUND AND PURPOSE: Non-anatomic bone tunnel placement is the most common cause of a failed ACL reconstruction. Accurate and reproducible methods to visualize and document bone tunnel placement are therefore important. We evaluated the reliability of standard radiographs, CT scans, and a 3-dimensional (3D) virtual reality (VR) approach in visualizing and measuring ACL reconstruction bone tunnel placement. METHODS: 50 consecutive patients who underwent single-bundle ACL reconstructions were evaluated postoperatively by standard radiographs, CT scans, and 3D VR images. Tibial and femoral tunnel positions were measured by 2 observers using the traditional methods of Amis, Aglietti, Hoser, Stäubli, and the method of Benereau for the VR approach. RESULTS: The tunnel was visualized in 50-82% of the standard radiographs and in 100% of the CT scans and 3D VR images. Using the intraclass correlation coefficient (ICC), the inter- and intraobserver agreement was between 0.39 and 0.83 for the standard femoral and tibial radiographs. CT scans showed an ICC range of 0.49-0.76 for the inter- and intraobserver agreement. The agreement in 3D VR was almost perfect, with an ICC of 0.83 for the femur and 0.95 for the tibia. INTERPRETATION: CT scans and 3D VR images are more reliable in assessing postoperative bone tunnel placement following ACL reconstruction than standard radiographs.

Larger First-Trimester Placental Volumetric Parameters Are Associated With Lower Pressure and More Flow-Mediated Vasodilation of the Fetoplacental Vasculature After Delivery.

OBJECTIVE: To explore the correlation between in vivo placental volumetric parameters in the first trimester of pregnancy and ex vivo parameters of fetoplacental vascular function after delivery. METHODS: In ten singleton physiological pregnancies, placental volume (PV) and uteroplacental vascular volume (uPVV) were measured offline in three-dimensional ultrasound volumes at 7, 9, and 11 weeks gestational age (GA) using Virtual Organ Analysis and Virtual Reality. Directly postpartum, term placentas were ex vivo dually perfused and pressure in the fetoplacental vasculature was measured to calculate baseline pressure (pressure after a washout period), pressure increase (pressure after a stepwise fetal flow rate increase of 1 mL/min up to 6 mL/min) and flow-mediated vasodilation (FMVD; reduction in inflow hydrostatic pressure on the fetal side at 6 mL/min flow rate). Correlations between in vivo and ex vivo parameters were assessed by Spearman's correlation coefficients (R). RESULTS: Throughout the first trimester, PV was negatively correlated with pressure increase (R growth = -0.84) and, at 11 weeks GA, also positively correlated with FMVD (R = 0.89). At 7 weeks GA, uPVV and uPVV/PV ratio were negatively correlated with pressure increase (R = -0.58 and R = -0.81, respectively) and positively correlated with FMVD (R = 0.62 and R = 0.90, respectively). DISCUSSION: Mainly in the early first trimester, larger placental volumetric parameters are associated with lower pressure and more FMVD in the fetoplacental vasculature after delivery. This may suggest that larger and/or more vascularized placentas in early pregnancy have better adaptive mechanisms and possibly lead to better pregnancy outcomes.

V-scope: design and implementation of an immersive and desktop virtual reality volume visualization system.

In this paper we present a new implementation of the virtual reality workstation concept. Based on an application originally developed for immersive virtual environments such as CAVEs, V-Scope allows clinicians and researchers to investigate their three dimensional (3D) imaging data with truly 3D views and interactions. This greatly improves the understanding of the data, and allows the efficient measurement of volumes and distances in a way that was previously not possible.

Towards a rational design of faecal transplant analogues.

Faecal transplants (microbiota transfer) have shown to be promising therapies having a wide range of therapeutic applications. However, current safety considerations hamper further valorisation. As such, well designed faecal transplant analogues provide an interesting alternative to minimize possible safety aspects. However, to date little knowledge on how to rationally design such analogues exists. Here, we show by applying first order basic graph theory that such analogues dedicated to restoring a specific physiological functionality (a microbial guild) should consist of 5-6 species to maximize stability, efficiency, and minimize safety issues and production costs.