Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease.

BACKGROUND: Fetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. OBJECTIVES: This study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. METHODS: In this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. RESULTS: A total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). CONCLUSIONS: Among fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

Vision-controlled jetting for composite systems and robots.

Recreating complex structures and functions of natural organisms in a synthetic form is a long-standing goal for humanity1. The aim is to create actuated systems with high spatial resolutions and complex material arrangements that range from elastic to rigid. Traditional manufacturing processes struggle to fabricate such complex systems2. It remains an open challenge to fabricate functional systems automatically and quickly with a wide range of elastic properties, resolutions, and integrated actuation and sensing channels2,3. We propose an inkjet deposition process called vision-controlled jetting that can create complex systems and robots. Hereby, a scanning system captures the three-dimensional print geometry and enables a digital feedback loop, which eliminates the need for mechanical planarizers. This contactless process allows us to use continuously curing chemistries and, therefore, print a broader range of material families and elastic moduli. The advances in material properties are characterized by standardized tests comparing our printed materials to the state-of-the-art. We directly fabricated a wide range of complex high-resolution composite systems and robots: tendon-driven hands, pneumatically actuated walking manipulators, pumps that mimic a heart and metamaterial structures. Our approach provides an automated, scalable, high-throughput process to manufacture high-resolution, functional multimaterial systems.

Feasibility of MRI assessment of maternal-fetal oxygen transport and consumption relative to maternal position in healthy late gestational pregnancies.

Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O2 ) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow-up MRI was performed 6-months postpartum (n = 16/20). MRI techniques included phase-contrast and T1/T2 relaxometry for blood flow and oximetry imaging, respectively. O2 transport was measured in the following vessels (bilateral where appropriate): maternal abdominal descending aorta (DAoabdo ), IVC, ovarian, paraspinal veins (PSV), uterine artery (UtA) and external iliacs, and umbilical. Maternal cardiac output was measured by summing DAothoracic and superior vena cava flows. Supine mothers (n = 6) had lower cardiac output and O2 delivery in the DAoabdo , UtA and external iliac arteries, and higher PSV flow than those in either the left (n = 8) or right (n = 6) lateral positions during MRI. However, O2 consumption in the gravid uterus, fetus, placenta and lower limbs was unaffected by maternal positioning. The ratio of IVC/PSV flow decreased in supine mothers while ovarian venous flow and O2 saturation were unaltered, suggesting a major route of pelvic venous return unaffected by maternal position. Placental-fetal O2 transport and consumption were similar between left and right lateral maternal positions. In comparison to non-pregnant findings, DAoabdo and UtA O2 delivery and pelvic O2 consumption increased, while lower-limb consumption remained constant , despite reduced external iliac artery O2 delivery in late gestation. KEY POINTS: Though sleeping supine during the third trimester is associated with an increased risk of antepartum stillbirth, the underlying biological mechanisms are not fully understood. Maternal cardiac output and uteroplacental flow are reduced in supine mothers due to inferior vena caval compression from the weight of the gravid uterus. This MRI study provides a comprehensive circulatory assessment, demonstrating reduced maternal cardiac output and O2 delivery (uteroplacental, lower body) in supine compared to lateral positioning; however, O2 consumption (gravid uterus, fetus, placenta, lower limbs) was preserved. Unlike other mammalian species, the ovarian veins conduct substantial venous return from the human pregnant uterus that is unaffected by maternal positioning. Lumbar paraspinal venous flow increased in supine mothers. These observations may have important considerations during major pelvic surgery in pregnancy (i.e. placenta percreta). Future studies should address the importance of maternal positioning as a potential tool to deliver improved perinatal outcomes in pregnancies with compromised uteroplacental O2 delivery.

Analyzing Continuous Physiologic Data to Find Hemodynamic Signatures Associated With New Brain Injury After Congenital Heart Surgery.

Continuous data capture technology is becoming more common. Establishing analytic approaches for continuous data could aid in understanding the relationship between physiology and clinical outcomes. OBJECTIVES: Our objective was to design a retrospective analysis for continuous physiologic measurements and their relationship with new brain injury over time after cardiac surgery. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study in the Cardiac Critical Care Unit at the Hospital for Sick Children in patients after repair of transposition of the great arteries (TGA) or single ventricle (SV) lesions. MAIN OUTCOMES AND MEASURES: Continuously acquired physiologic measurements for up to 72 hours after cardiac surgery were analyzed for association with new brain injury by MRI. Distributions of heart rate (HR), systolic blood pressure (BP), and oxygen saturation (Spo2) for SV and TGA were analyzed graphically and with descriptive statistics over postoperative time for data-driven variable selection. Mixed-effects regression analyses characterized relationships between HR, BP, and Spo2 and new brain injury over time while accounting for variation between patients, measurement heterogeneity, and missingness. RESULTS: Seventy-seven patients (60 TGA; 17 SV) were included. New brain injury was seen in 26 (34%). In SV patients, with and without new brain injury, respectively, in the first 24 hours after cardiac surgery, the median (interquartile range) HR was 172.0 beats/min (bpm) (169.7-176.0 bpm) versus 159.6 bpm (145.0-167.0 bpm); systolic BP 74.8 (67.9-78.5 mm Hg) versus 68.9 mm Hg (61.6-70.9 mm Hg). Higher postoperative HR (parameter estimate, 19.4; 95% CI, 7.8-31; p = 0.003 and BP, 8.6; 1.3-15.8; p = 0.024) were associated with new brain injury in SV patients. The strength of this relationship decreased with time. CONCLUSIONS AND RELEVANCE: Retrospective analysis of continuous physiologic measurements can provide insight into changes in postoperative physiology over time and their relationship with new brain injury. This technique could be applied to assess relationships between physiologic data and many patient interventions or outcomes.

Volumetric Fetal Flow Imaging With Magnetic Resonance Imaging.

Fetal development relies on a complex circulatory network. Accurate assessment of flow distribution is important for understanding pathologies and potential therapies. In this paper, we demonstrate a method for volumetric imaging of fetal flow with magnetic resonance imaging (MRI). Fetal MRI faces challenges: small vascular structures, unpredictable motion, and inadequate traditional cardiac gating methods. Here, orthogonal multislice stacks are acquired with accelerated multidimensional radial phase contrast (PC) MRI. Slices are reconstructed into flow sensitive time-series images with motion correction and image-based cardiac gating. They are then combined into a dynamic volume using slice-to-volume reconstruction (SVR) while resolving interslice spatiotemporal coregistration. Compared to prior methods, this approach achieves higher spatiotemporal resolution ( 1×1×1 mm3, ~30 ms) with reduced scan time - important features for the quantification of flow through small fetal structures. Validation is demonstrated in adults by comparing SVR with 4D radial PCMRI (flow bias and limits of agreement: -1.1 ml/s and [-11.8 9.6] ml/s). Feasibility is demonstrated in late gestation fetuses by comparing SVR with 2D Cartesian PCMRI (flow bias and limits of agreement: -0.9 ml/min/kg and [-39.7 37.8] ml/min/kg). With SVR, we demonstrate complex flow pathways (such as parallel flow streams in the proximal inferior vena cava, preferential shunting of blood from the ductus venosus into the left atrium, and blood from the brain leaving the heart through the main pulmonary artery) for the first time in human fetal circulation. This method allows for comprehensive evaluation of the fetal circulation and enables future studies of fetal physiology.

Impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in patients with Ebstein anomaly and tricuspid valve dysplasia.

OBJECTIVES: To evaluate the impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in severe Ebstein anomaly and tricuspid valve dysplasia. METHODS: Thirty-four fetuses with Ebstein anomaly/tricuspid valve dysplasia were referred from 2013 to 2019 for fetal echocardiography and clinical management. Nineteen fetuses with Ebstein anomaly/tricuspid valve dysplasia and 30 controls underwent cardiovascular magnetic resonance to quantify the fetal blood flow and to calculate cerebral oxygen delivery (cDO2) and consumption (cVO2). The 3D steady-state free precession acquisition was used to measure fetal brain volume. Surgical outcome, brain MRI, and neurodevelopmental follow-up were reviewed. RESULTS: Twenty-six fetuses were live born (76%) and survival (65%) at a mean follow-up of 4 years. Nine fetuses had a brain MRI before discharge, and all had clinically silent injuries and volume loss. At 18 months, five single-ventricle patients had a neurodevelopmental delay in cognition and language (mean percentile: 11th), with gross-motor skills more affected than fine-motor skills (mean percentiles: 4th and 34th). Fetuses with Ebstein anomaly/tricuspid valve dysplasia had smaller brains, lower combined ventricular output, ascending aorta, superior caval vien and umbilical vein flows, lower oxygen saturation in ascending aorta and superior caval vien, lower cDO2 and cVO2 (p < 0.05). Superior caval vien/combined ventricular output and descending aorta/combined ventricular output ratios were lower in fetuses with circular shunt (p < 0.05). Fetuses requiring the Starnes procedure tended to have smaller brains, lower combined ventricular output, superior caval vien, descending aorta, and umbilical vein flows. CONCLUSIONS: All patients with Ebstein anomaly/tricuspid valve dysplasia are at high risk of neurodevelopmental delay and warrant follow-up. Fetal cardiovascular magnetic resonance revealed impaired brain growth with diminished cerebral blood flow and cDO2, the extenting dependent on the severity of the haemodynamic compromise.

Prevalence, Risk Factors, and Impact of Preoperative Seizures in Neonates With Congenital Heart Disease.

PURPOSE: The purpose of this study was to assess the prevalence, risk factors, and impact of electrographic seizures in neonates with complex congenital heart disease before cardiac surgery. METHODS: A cohort of 31 neonates with congenital heart disease monitored preoperatively with continuous video-EEG (cEEG) was first reviewed for electrographic seizure burden and EEG background abnormalities. Second, cEEG findings were correlated with brain MRI and 18-month outcomes. RESULTS: Continuous video-EEG was recorded preoperatively for a median duration of 20.5 hours (range, 2.5-93.5 hours). The five neonates (16%; 95% confidence interval, 5.5% to 34%) with seizures detected on cEEG in the preoperative period had a diagnosis of transposition of the great arteries or similar physiology, detected in four of five postnatally. None of the 157 recorded electrographic seizures had a clinical correlate. The median time to first seizure was 65 minutes (range, 6-300 minutes) after cEEG hookup. The median maximum hourly seizure burden was 12.4 minutes (range, 7-23 minutes). Before the first electrographic seizure, a prolonged interburst interval (>10 seconds) was not associated with seizures (coefficient 1.2; 95% confidence interval, -1.1 to 3.6). MRI brain lesions were three times more common in neonates with seizures. Sharp wave transients on cEEG were associated with delayed opercular development. CONCLUSIONS: In this cohort, preoperative electrographic seizures were common, were all subclinical, and were associated with MRI brain injury and postnatal diagnosis of transposition of the great arteries. The findings motivate further study of the mechanisms of preoperative brain injury, particularly among neonates with a postnatal diagnosis of transposition of the great arteries.

Fetal brain issues in congenital heart disease.

Following the improvements in the clinical management of patients with congenital heart disease (CHD) and their increased survival, neurodevelopmental outcome has become an emerging priority in pediatric cardiology. Large-scale efforts have been made to protect the brain during the postnatal, surgical, and postoperative period; however, the presence of brain immaturity and injury at birth suggests in utero and peripartum disturbances. Over the past decade, there has been considerable interest and investigations on fetal brain growth in the setting of CHD. Advancements in fetal brain imaging have identified abnormal brain development in fetuses with CHD from the macrostructural (brain volumes and cortical folding) down to the microstructural (biochemistry and water diffusivity) scale, with more severe forms of CHD showing worse disturbances and brain abnormalities starting as early as the first trimester. Anomalies in common genetic developmental pathways and diminished cerebral substrate delivery secondary to altered cardiovascular physiology are the forefront hypotheses, but other factors such as impaired placental function and maternal psychological stress have surfaced as important contributors to fetal brain immaturity in CHD. The characterization and timing of fetal brain disturbances and their associated mechanisms are important steps for determining preventative prenatal interventions, which may provide a stronger foundation for the developing brain during childhood.

Maternal hyperoxygenation in congenital heart disease.

The importance of prenatal diagnosis and fetal intervention has been increasing as a preventative strategy for improving the morbidity and mortality in congenital heart disease (CHD). The advancements in medical imaging technology have greatly enhanced our understanding of disease progression, assessment, and impact in those with CHD. In particular, there has been a growing focus on improving the morbidity and mortality of fetuses diagnosed with left-sided lesions. The disruption of fetal hemodynamics resulting from poor structural developmental of the left outflow tract during cardiogenesis is considered a major factor in the progressive lethal underdevelopment of the left ventricle (LV). This positive feedback cycle of inadequate flow and underdevelopment of the LV leads to a disrupted fetal circulation, which has been described to impact fetal brain growth where systemic outflow is poor and, in some cases, the fetal lungs in the setting of a restrictive interatrial communication. For the past decade, maternal hyperoxygenation (MH) has been investigated as a diagnostic tool to assess the pulmonary vasculature and a therapeutic agent to improve the development of the heart and brain in fetuses with CHD with a focus on left-sided cardiac defects. This review discusses the findings of these studies as well as the utility of acute and chronic administration of MH in CHD.

Maternal and Fetal Hemodynamic Adaptations to Pregnancy and Clinical Outcomes in Maternal Cardiac Disease.

BACKGROUND: Although insufficient maternal cardiac output (CO) has been implicated in poor outcomes in mothers with heart disease (HD), maternal-fetal interactions remain incompletely understood. We sought to quantify maternal-fetal hemodynamics with the use of magnetic resonance imaging (MRI) and explore their relationship with adverse events. METHODS: Pregnant women with moderate or severe HD (n = 22; mean age 32 ± 5 years) were compared with healthy control women (n = 21; 34 ± 3 years). An MRI was performed during the third trimester at peak output (maternal-fetal) and 6 months postpartum with return of maternal hemodynamics to baseline (reference). Phase-contrast MRI was used for flow quantification and was combined with T1/T2 relaxometry for derivation of fetal oxygen delivery/consumption. RESULTS: Third-trimester CO and cardiac index (CI) measurements were similar in HD and control groups (CO 7.2 ± 1.5 vs 7.3 ± 1.6 L/min, P = 0.79; CI 4.0 ± 0.7 vs 4.3 ± 0.7 L/min/m,2P = 0.28). However, the magnitude of CO/CI increase (Δ, peak pregnancy - reference) in the HD group exceeded that in the control group (CO 46 ± 24% vs 27 ± 16% [P = 0.007]; CI 51 ± 28% vs 28 ± 17% [P = 0.005]). Fetal growth and oxygen delivery/consumption were similar between groups. Adverse cardiovascular outcomes (nonmutually exclusive) in 6 HD women included arrhythmia (n = 4), heart failure (n = 2), and hypertensive disorder of pregnancy (n = 1); premature delivery was observed in 2 of these women. The odds of a maternal cardiovascular event were inversely associated with peak CI (odds ratio 0.10, 95% confidence interval 0.001-0.86; P = 0.04) and Δ,CI (0.02, 0.001-0.71; P = 0.03). CONCLUSIONS: Maternal-fetal hemodynamics can be well characterised in pregnancy with the use of MRI. Impaired adaptation to pregnancy in women with HD appears to be associated with development of adverse outcomes of pregnancy.

An MRI approach to assess placental function in healthy humans and sheep.

KEY POINTS: Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( VO2 ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and VO2 by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental VO2 by MRI was ∼4 ml min-1  kg-1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental VO2 , which involves the quantification of maternal- and fetal-placental blood flows, fetal oxygen delivery and VO2 , and the oxygen gradient between uterine- and umbilical-venous blood, providing a comprehensive assessment of placental function with clinical potential. ABSTRACT: It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ( VO2 ) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non-invasively quantify in utero placental and fetal oxygen delivery ( DO2 ) and VO2 in healthy humans and sheep. Women (n = 20) and Merino sheep (n = 10; 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively; mean ± SD). Blood flow (phase-contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine- and umbilical-placental vessels, allowing calculation of uteroplacental and fetal DO2 and VO2 . Maternal DO2 (ml min-1  kg-1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal DO2 (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal VO2 (ml min-1  kg-1 fetus; uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281; fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal VO2 ratio did not change with age (human, P = 0.256; sheep, P = 0.121). Human umbilical blood flow (ml min-1  kg-1 fetus) decreased with advancing age (P = 0.008), while fetal VO2 was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal VO2 was preserved through stable umbilical flow (ml min-1  kg-1 ; P = 0.443) and oxygen extraction (P = 0.582). MRI derived measurements of uteroplacental and fetal VO2 between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical 'placental function test'.

The association between parent stress, coping and mental health, and neurodevelopmental outcomes of infants with congenital heart disease.

Caring for the complex needs of a child with congenital heart disease (CHD) can place significant burden on the family. Parent mental health and coping have important influences on resilience and neurodevelopmental outcomes in children with CHD. Objectives: To describe the uptake of a cardiac neurodevelopmental program (CNP), examine parent mental health and coping specific to parenting a child with CHD, and explore the relationship between parent mental health and child neurodevelopmental outcomes. Method: Implementation and uptake of the CNP was examined, and forty-four parents of children with CHD completed the DASS and RSQ-CHD. Results: The CNP showed significant uptake in follow-up and interventions offered including 100% completed brain MRIs of eligible patients, 35% increase in neonatal neurology consults, and 100% of families counselled on neurodevelopmental outcomes. A significant proportion of parents endorsed moderate/severe levels of anxiety (25%), depression (20%), and CHD-specific stress. Parents predominantly engaged in secondary control engagement coping (F(2,64)=75.04, p<.001, ηp2=.70). Secondary control engagement coping was associated with lower parent total stress (r=-.48, p=.006) and anxiety (r=-.47, p=.009). Higher parent stress was associated with higher anxiety (r=.45, p=.016), depression (r=.37, p=.05), more severe types of CHD (r=.35, p=.048), older child age (t(30)= -2.33, p=.03), and lower child cognitive scores (r=-.37, p=.045). More severe types of CHD were associated with lower language scores (F(3,35)=3.50, p=.03). Conclusions: This study highlights the relationship between parent mental health and early child cognitive outcomes in CHD and helps inform models of psychological care to reduce family burden and improve child outcomes.

Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation.

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the recognized standard-of-care for blood flow quantification based on phase contrast MRI. While such measurement of blood flow has been possible in adults for decades, methods to extend this capability to fetal blood flow have only recently been developed. Fetal blood flow quantification in major vessels is important for monitoring fetal pathologies such as congenital heart disease (CHD) and fetal growth restriction (FGR). CHD causes alterations in the cardiac structure and vasculature that change the course of blood in the fetus. In FGR, the path of blood flow is altered through the dilation of shunts such that the oxygenated blood supply to the brain is increased. Blood flow quantification enables assessment of the severity of the fetal pathology, which in turn allows for suitable in utero patient management and planning for postnatal care. The primary challenges of applying phase contrast MRI to the human fetus include small blood vessel size, high fetal heart rate, potential MRI data corruption due to maternal respiration, unpredictable fetal movements, and lack of conventional cardiac gating methods to synchronize data acquisition. Here, we describe recent technical developments from our lab that have enabled the quantification of fetal blood flow using phase contrast MRI, including advances in accelerated imaging, motion compensation, and cardiac gating.

Fetal Flow Quantification in Great Vessels Using Motion-Corrected Radial Phase Contrast MRI: Comparison With Cartesian.

BACKGROUND: Phase contrast MRI in the great vessels is a potential clinical tool for managing fetal pathologies. One challenge is the uncontrollable fetal motion, potentially corrupting flow quantifications. PURPOSE: To demonstrate improvements in fetal blood flow quantification in great vessels using retrospectively motion-corrected golden-angle radial phase contrast MRI relative to Cartesian phase contrast MRI. STUDY TYPE: Method comparison. PHANTOM/SUBJECTS: Computer simulation. Seventeen pregnant volunteers. FIELD STRENGTH/SEQUENCE: 1.5T and 3T. Cartesian and golden-angle radial phase contrast MRI. ASSESSMENT: Through computer simulations, radial (with and without retrospective motion correction) and Cartesian phase contrast MRI were compared using flow deviations. in vivo Cartesian and radial phase contrast MRI measurements and reconstruction qualities were compared in pregnancies. Cartesian data were reconstructed into gated reconstructions (CINEs) after cardiac gating with metric optimized gating (MOG). For radial data, real-time reconstructions were performed for motion correction and MOG followed by CINE reconstructions. STATISTICAL TESTS: Wilcoxon signed-rank test. Linear regression. Bland-Altman plots. Student's t-test. RESULTS: Simulations showed significant improvements (P < 0.05) in flow accuracy and reconstruction quality with motion correction ([mean/peak] flow errors with ±5 mm motion corruption: Cartesian [35 ± 1/115 ± 7] mL/s, motion uncorrected radial [25 ± 1/75 ± 2] mL/s and motion-corrected radial [1.0 ± 0.5/-5 ± 1] mL/s). in vivo Cartesian reconstructions without motion correction had lower quality than the motion-corrected radial reconstructions (P < 0.05). Across all fetal mean flow measurements, the bias [limits of agreement] between the two measurements were -0.2 [-76, 75] mL/min/kg, while the linear regression coefficients were (Mradial = 0.81 × MCartesian + 29.8 [mL/min/kg], r2 = 0.67). The corresponding measures for the peak fetal flows were -23 [-214, 167] mL/min/kg and (Pradial = 0.95 × PCartesian -1.2 [mL/min/kg], r2 = 0.80). Cartesian reconstructions of low quality showed significantly higher estimated mean and peak (P < 0.05) flows than the corresponding radial reconstructions. DATA CONCLUSION: Simulations showed that radial phase contrast MRI with motion compensation improved flow accuracy. For fetal measurements, motion-corrected radial reconstructions showed better image quality than, and different flow values from, Cartesian reconstructions. Level of Evidence 1. Technical Efficacy Stage 1. J. MAGN. RESON. IMAGING 2021;53:540-551.

Fetal brain growth and risk of postnatal white matter injury in critical congenital heart disease.

OBJECTIVE: To test the hypothesis that delayed brain development in fetuses with d-transposition of the great arteries or hypoplastic left heart syndrome heightens their postnatal susceptibility to acquired white matter injury. METHODS: This is a cohort study across 3 sites. Subjects underwent fetal (third trimester) and neonatal preoperative magnetic resonance imaging of the brain to measure total brain volume as a measure of brain maturity and the presence of acquired white matter injury after birth. White matter injury was categorized as no-mild or moderate-severe based on validated grading criteria. Comparisons were made between the injury groups. RESULTS: A total of 63 subjects were enrolled (d-transposition of the great arteries: 37; hypoplastic left heart syndrome: 26). White matter injury was present in 32.4% (n = 12) of d-transposition of the great arteries and 34.6% (n = 8) of those with hypoplastic left heart syndrome. Overall total brain volume (taking into account fetal and neonatal scan) was significantly lower in those with postnatal moderate-severe white matter injury compared with no-mild white matter injury after adjusting for age at scan and site in d-transposition of the great arteries (coefficient: 14.8 mL, 95% confidence interval, -28.8 to -0.73, P = .04). The rate of change in total brain volume from fetal to postnatal life did not differ by injury group. In hypoplastic left heart syndrome, no association was noted between overall total brain volume and change in total brain volume with postnatal white matter injury. CONCLUSIONS: Lower total brain volume beginning in late gestation is associated with increased risk of postnatal moderate-severe white matter injury in d-transposition of the great arteries but not hypoplastic left heart syndrome. Rate of brain growth was not a risk factor for white matter injury. The underlying fetal and perinatal physiology has different implications for postnatal risk of white matter injury.

Fetal cardiovascular magnetic resonance imaging.

Fetal cardiovascular MRI is showing promise as a clinical diagnostic tool in the setting of congenital heart disease when the cardiac anatomy is unresolved by US or when complementary quantitative data on blood flow, oxygen saturation and hematocrit are required to aid in management. Compared with postnatal cardiovascular MRI, prenatal cardiovascular MRI still has some technical limitations. However, ongoing technical advances continue to improve the robustness and usability of fetal cardiovascular MRI. In this review, we provide an overview of the state of the art of fetal cardiovascular MRI and summarize the current focus of clinical application for this versatile technique.

Complicated ventricular arrhythmia and hematologic myeloproliferative disorder in RIT1-associated Noonan syndrome: Expanding the phenotype and review of the literature.

BACKGROUND: Noonan syndrome is an autosomal dominant disorder secondary to RASopathies, which are caused by germ-line mutations in genes encoding components of the RAS mitogen-activated protein kinase pathway. RIT1 (OMIM *609591) was recently reported as a disease gene for Noonan syndrome. METHODS AND RESULTS: We present a patient with RIT1-associated Noonan syndrome, who in addition to the congenital heart defect, had monocytosis, myeloproliferative disorder, and accelerated idioventricular rhythm that was associated with severe hemodynamic instability. Noonan syndrome was suspected given the severe pulmonary stenosis, persistent monocytosis, and "left-shifted" complete blood counts without any evidence of an infectious process. Genetic testing revealed that the patient had a heterozygous c.221 C>G (pAla74Gly) mutation in the RIT1. CONCLUSION: We report a case of neonatal Noonan syndrome associated with RIT1 mutation. The clinical suspicion for Noonan syndrome was based only on the congenital heart defect, persistent monocytosis, and myeloproliferative process as the child lacked all other hallmarks characteristics of Noonan syndrome. However, the patient had an unusually malignant ventricular dysrhythmia that lead to his demise. The case highlights the fact that despite its heterogeneous presentation, RIT1-associated Noonan syndrome can be extremely severe with poor outcome.

Decreased Brain Volumes and Infants With Congenital Heart Disease Undergoing Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: The aims of this study were to: i) determine the spectrum of brain injury and ii) compare brain volumes between pre- and postoperative brain MRI in the infants receiving extracorporeal membrane oxygenation compared with those who did not require extracorporeal membrane oxygenation. DESIGN: Cohort study of infants with D-transposition of the great arteries or single ventricle physiology. Brain volume (cm) was measured using a segmentation of a volumetric T1-weighted gradient echo sequence. Brain imaging findings (intraventricular hemorrhage, white matter injuries, and stroke) were analyzed with respect to known clinical risk factors for brain injury and adverse neurodevelopmental outcomes. Clinical factors were collected by retrospective chart review. The association between brain volume and extracorporeal membrane oxygenation was evaluated using generalized estimating equations to account for repeated measures. SETTING: Prospective and single-centered study. PATIENTS: One hundred nine infants (median gestational age, 39.1 wk) with D-transposition of the great arteries (n = 77) or single ventricle physiology (n = 32) were studied pre- and postoperatively with MRI as per clinical protocol. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 28 infants (26%) receiving extracorporeal membrane oxygenation, 19 (68%) were supported with extracorporeal membrane oxygenation once, and nine (32%) were supported 2-4 times. On postoperative MRI, new white matter injury was found in only five (17%) of the extracorporeal membrane oxygenation infants versus 40 (49%) in the non-extracorporeal membrane oxygenation group (p = 0.073). The rate of stroke (9% vs 10%), intraventricular hemorrhage (24% vs 29%), and hypoxic ischemia (3% vs 14%) did not differ between the non-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation groups (all p > 0.5). Accounting for D-transposition of the great arteries or single ventricle physiology diagnosis, infants requiring extracorporeal membrane oxygenation had slower brain volume with single (ß = -1.67) or multiple extracorporeal membrane oxygenation runs ([ß = -6.54]; overall interaction p = 0.012). CONCLUSIONS: Patients with d-transposition of the great arteries or single ventricle physiology undergoing extracorporeal membrane oxygenation at our center have a similar incidence of brain injury but more significant impairment of perioperative brain volumes than those not requiring extracorporeal membrane oxygenation.

Understanding Fetal Hemodynamics Using Cardiovascular Magnetic Resonance Imaging.

Human fetal circulatory physiology has been investigated extensively using grey-scale ultrasound, which provides excellent visualization of cardiac anatomy and function, while velocity profiles in the heart and vessels can be interrogated using Doppler. Measures of cerebral and placental vascular resistance, as well as indirect measures of intracardiac pressure obtained from the velocity waveform in the ductus venosus are routinely used to guide the management of fetal cardiovascular and placental disease. However, the characterization of some key elements of cardiovascular physiology such as vessel blood flow and the oxygen content of blood in the arteries and veins, as well as fetal oxygen delivery and consumption are not readily measured using ultrasound. To study these parameters, we have historically relied on data obtained using invasive measurements made in animal models, which are not equivalent to the human in every respect. Over recent years, a number of technical advances have been made that have allowed us to examine the human fetal circulatory system using cardiovascular magnetic resonance (CMR). The combination of vessel blood flow measurements made using cine phase contrast magnetic resonance imaging and vessel blood oxygen saturation and hematocrit measurements made using T1 and T2 mapping have enabled us to emulate those classic fetal sheep experiments defining the distribution of blood flow and oxygen transport across the fetal circulation in the human fetus. In addition, we have applied these techniques to study the relationship between abnormal fetal cardiovascular physiology and fetal development in the setting of congenital heart disease and placental insufficiency. CMR has become an important diagnostic tool in the assessment of cardiovascular physiology in the setting of postnatal cardiovascular disease, and is now being applied to the fetus to enhance our understanding of normal and abnormal fetal circulatory physiology and its impact on fetal well-being.