Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental perfusion imaging was performed using velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with whole-placenta coverage. In pregnancies with fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age; however, no such correlation was found in healthy pregnancies. Also, global placental perfusion was significantly higher in fetal CHD versus controls, in the lateral side-lying patient position versus supine, and in the posterior placental position versus anterior placental position. This study reports for the first time non-invasive whole-placenta perfusion imaging in utero. These data suggest that placental VSASL may serve as a potential biomarker of placental dysfunction in fetuses diagnosed with CHD

Advanced MR imaging of the placenta: Exploring the in utero placenta-brain connection.

The placenta is a vital organ necessary for the healthy neurodevelopment of the fetus. Despite the known associations between placental dysfunction and neurologic impairment, there is a paucity of tools available to reliably assess in vivo placental health and function. Existing clinical tools for placental assessment remain insensitive in predicting and assessing placental well-being. Advanced MRI techniques hold significant promise for the dynamic, non-invasive, real-time assessment of placental health and identification of early placental-based disorders. In this review, we summarize the available clinical tools for placental assessment including ultrasound, Doppler, and conventional MRI. We then explore the emerging role of advanced placental MR imaging techniques for supporting the developing fetus, appraise the strengths and limitations of quantitative MRI in identifying early markers of placental dysfunction for improved pregnancy monitoring and fetal outcomes

Robust preprocessing for stimulus-based functional MRI of the moving fetus.

Fetal motion manifests as signal degradation and image artifact in the acquired time series of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We present a robust preprocessing pipeline to specifically address fetal and placental motion-induced artifacts in stimulus-based fMRI with slowly cycled block design in the living fetus. In the proposed pipeline, motion correction is optimized to the experimental paradigm, and it is performed separately in each phase as well as in each region of interest (ROI), recognizing that each phase and organ experiences different types of motion. To obtain the averaged BOLD signals for each ROI, both misaligned volumes and noisy voxels are automatically detected and excluded, and the missing data are then imputed by statistical estimation based on local polynomial smoothing. Our experimental results demonstrate that the proposed pipeline was effective in mitigating the motion-induced artifacts in stimulus-based fMRI data of the fetal brain and placenta

Genome-wide neonatal epigenetic changes associated with maternal exposure to the COVID-19 pandemic.

BACKGROUND: During gestation, stressors to the fetus, including viral exposure or maternal psychological distress, can fundamentally alter the neonatal epigenome, and may be associated with long-term impaired developmental outcomes. The impact of in utero exposure to the COVID-19 pandemic on the newborn epigenome has yet to be described. METHODS: This study aimed to determine whether there are unique epigenetic signatures in newborns who experienced otherwise healthy pregnancies that occurred during the COVID-19 pandemic (Project RESCUE). The pre-pandemic control and pandemic cohorts (Project RESCUE) included in this study are part of a prospective observational and longitudinal cohort study that evaluates the impact of elevated prenatal maternal stress during the COVID-19 pandemic on early childhood neurodevelopment. Using buccal swabs collected at birth, differential DNA methylation analysis was performed using the Infinium MethylationEPIC arrays and linear regression analysis. Pathway analysis and gene ontology enrichment were performed on resultant gene lists. RESULTS: Widespread differential methylation was found between neonates exposed in utero to the pandemic and pre-pandemic neonates. In contrast, there were no apparent epigenetic differences associated with maternal COVID-19 infection during pregnancy. Differential methylation was observed among genomic sites that underpin important neurological pathways that have been previously reported in the literature to be differentially methylated because of prenatal stress, such as NR3C1. CONCLUSIONS: The present study reveals potential associations between exposure to the COVID-19 pandemic during pregnancy and subsequent changes in the newborn epigenome. While this finding warrants further investigation, it is a point that should be considered in any study assessing newborn DNA methylation studies obtained during this period, even in otherwise healthy pregnancies

Genome-wide neonatal epigenetic changes associated with maternal exposure to the COVID-19 pandemic

Abstract Background During gestation, stressors to the fetus, including viral exposure or maternal psychological distress, can fundamentally alter the neonatal epigenome, and may be associated with long-term impaired developmental outcomes. The impact of in utero exposure to the COVID-19 pandemic on the newborn epigenome has yet to be described. Methods This study aimed to determine whether there are unique epigenetic signatures in newborns who experienced otherwise healthy pregnancies that occurred during the COVID-19 pandemic (Project RESCUE). The pre-pandemic control and pandemic cohorts (Project RESCUE) included in this study are part of a prospective observational and longitudinal cohort study that evaluates the impact of elevated prenatal maternal stress during the COVID-19 pandemic on early childhood neurodevelopment. Using buccal swabs collected at birth, differential DNA methylation analysis was performed using the Infinium MethylationEPIC arrays and linear regression analysis. Pathway analysis and gene ontology enrichment were performed on resultant gene lists. Results Widespread differential methylation was found between neonates exposed in utero to the pandemic and pre-pandemic neonates. In contrast, there were no apparent epigenetic differences associated with maternal COVID-19 infection during pregnancy. Differential methylation was observed among genomic sites that underpin important neurological pathways that have been previously reported in the literature to be differentially methylated because of prenatal stress, such as NR3C1. Conclusions The present study reveals potential associations between exposure to the COVID-19 pandemic during pregnancy and subsequent changes in the newborn epigenome. While this finding warrants further investigation, it is a point that should be considered in any study assessing newborn DNA methylation studies obtained during this period, even in otherwise healthy pregnancies

Detrended fluctuation analysis of non-stationary cardiac beat-to-beat interval of sick infants

We performed detrended fluctuation analysis (DFA) of cardiac beat-to-beat intervals (RRis) collected from sick newborn infants over 1–4 day periods. We calculated four different metrics from the DFA fluctuation function: the DFA exponents $\alpha_{L}$ (>40 beats up to one-fourth of the record length), $\alpha_{s}$ (15–30 beats), root-mean-square (RMS) fluctuation on a short-time scale (20–50 beats), and RMS fluctuation on a long-time scale (110–150 beats). Except $\alpha_{L}$ , all metrics clearly distinguished two groups of newborn infants (favourable vs. adverse) with well-characterized outcomes. However, the RMS fluctuations distinguished the two groups more consistently over time compared to $\alpha_{S}$ . Furthermore, RMS distinguished the RRi of the two groups earlier compared to the DFA exponent. In all the three measures, the favourable outcome group displayed higher values, indicating a higher magnitude of (auto-)correlation and variability, thus normal physiology, compared to the adverse outcome group

Non-invasive measurement of biochemical profiles in the healthy fetal brain

© 2020 The Author(s) Proton magnetic resonance spectroscopy (1H-MRS) of the fetal brain can be used to study emerging metabolite profiles in the developing brain. Identifying early deviations in brain metabolic profiles in high-risk fetuses may offer important adjunct clinical information to improve surveillance and management during pregnancy. Objective: To investigate the normative trajectory of the fetal brain metabolites during the second half of gestation, and to determine the impact of using different Cramer-Rao Lower Bounds (CRLB) threshold on metabolite measurements using magnetic resonance spectroscopy. Study design: We prospectively enrolled 219 pregnant women with normal fetal ultrasound and biometric measures. We performed a total of 331 fetal 1H-MRS studies with gestational age in the rage of 18–39 weeks with 112 of the enrolled participants scanned twice. All the spectra in this study were acquired on a GE 1.5 T scanner using long echo-time of 144 ​ms and analyzed in LCModel. Results: We successfully acquired and analyzed fetal 1H-MRS with a success rate of 93%. We observed increases in total NAA, total creatine, total choline, scyllo inositol and total NAA-to-total choline ratio with advancing GA. Our results also showed faster increases in total NAA and total NAA-to-total choline ratio during the third trimester compared to the second trimester. We also observed faster increases in total choline and total NAA in female fetuses. Increasing the Cramer-Rao lower bounds threshold progressively from 100% to 40%–20% increased the mean metabolite concentrations and decreased the number of observations available for analysis. Conclusion: We report serial fetal brain biochemical profiles in a large cohort of health fetuses studied twice in gestation with a high success rate in the second and third trimester of pregnancy. We present normative in-vivo fetal brain metabolite trajectories over a 21-week gestational period which can be used to non-invasively measure and monitor brain biochemistry in the healthy and high-risk fetus

Non-invasive measurement of biochemical profiles in the healthy fetal brain.

© 2020 The Author(s) Proton magnetic resonance spectroscopy (1H-MRS) of the fetal brain can be used to study emerging metabolite profiles in the developing brain. Identifying early deviations in brain metabolic profiles in high-risk fetuses may offer important adjunct clinical information to improve surveillance and management during pregnancy. Objective: To investigate the normative trajectory of the fetal brain metabolites during the second half of gestation, and to determine the impact of using different Cramer-Rao Lower Bounds (CRLB) threshold on metabolite measurements using magnetic resonance spectroscopy. Study design: We prospectively enrolled 219 pregnant women with normal fetal ultrasound and biometric measures. We performed a total of 331 fetal 1H-MRS studies with gestational age in the rage of 18–39 weeks with 112 of the enrolled participants scanned twice. All the spectra in this study were acquired on a GE 1.5 T scanner using long echo-time of 144 ​ms and analyzed in LCModel. Results: We successfully acquired and analyzed fetal 1H-MRS with a success rate of 93%. We observed increases in total NAA, total creatine, total choline, scyllo inositol and total NAA-to-total choline ratio with advancing GA. Our results also showed faster increases in total NAA and total NAA-to-total choline ratio during the third trimester compared to the second trimester. We also observed faster increases in total choline and total NAA in female fetuses. Increasing the Cramer-Rao lower bounds threshold progressively from 100% to 40%–20% increased the mean metabolite concentrations and decreased the number of observations available for analysis. Conclusion: We report serial fetal brain biochemical profiles in a large cohort of health fetuses studied twice in gestation with a high success rate in the second and third trimester of pregnancy. We present normative in-vivo fetal brain metabolite trajectories over a 21-week gestational period which can be used to non-invasively measure and monitor brain biochemistry in the healthy and high-risk fetus

Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury