Towards an integrated neonatal brain and cardiac examination capability at 7 T: electromagnetic field simulations and early phantom experiments using an 8-channel dipole array

Objective Neonatal brain and cardiac imaging would benefit from the increased signal-to-noise ratio levels at 7 T compared to lower field. Optimal performance might be achieved using purpose designed RF coil arrays. In this study, we introduce an 8-channel dipole array and investigate, using simulations, its RF performances for neonatal applications at 7 T. Methods The 8-channel dipole array was designed and evaluated for neonatal brain/cardiac configurations in terms of SAR efficiency (ratio between transmit-field and maximum specific-absorption-rate level) using adjusted dielectric properties for neonate. A birdcage coil operating in circularly polarized mode was simulated for comparison. Validation of the simulation model was performed on phantom for the coil array. Results The 8-channel dipole array demonstrated up to 46% higher SAR efficiency levels compared to the birdcage coil in neonatal configurations, as the specific-absorption-rate levels were alleviated. An averaged normalized root-mean-square-error of 6.7% was found between measured and simulated transmit field maps on phantom. Conclusion The 8-channel dipole array design integrated for neonatal brain and cardiac MR was successfully demonstrated, in simulation with coverage of the baby and increased SAR efficiency levels compared to the birdcage. We conclude that the 8Tx-dipole array promises safe operating procedures for MR imaging of neonatal brain and heart at 7 T.

Neonatal brain injury influences structural connectivity and childhood functional outcomes

Neonatal brain injury may impact brain development and lead to lifelong functional impairments. Hypoxic-ischemic encephalopathy (HIE) and congenital heart disease (CHD) are two common causes of neonatal brain injury differing in timing and mechanism. Maturation of whole-brain neural networks can be quantified during development using diffusion magnetic resonance imaging (dMRI) in combination with graph theory metrics. DMRI of 35 subjects with CHD and 62 subjects with HIE were compared to understand differences in the effects of HIE and CHD on the development of network topological parameters and functional outcomes. CHD newborns had worse 12–18 month language (P<0.01) and 30 month cognitive (P<0.01), language (P = 0.05), motor outcomes (P = 0.01). Global efficiency, a metric of brain integration, was lower in CHD (P = 0.03) than in HIE, but transitivity, modularity and small-worldness were similar. After controlling for clinical factors known to affect neurodevelopmental outcomes, we observed that global efficiency was highly associated with 30 month motor outcomes (P = 0.02) in both groups. To explore neural correlates of adverse language outcomes in CHD, we used hypothesis-based and data-driven approaches to identify pathways with altered structural connectivity. We found that connectivity strength in the superior longitudinal fasciculus (SLF) tract 2 was inversely associated with expressive language. After false discovery rate correction, a whole connectome edge analysis identified 18 pathways that were hypoconnected in the CHD cohort as compared to HIE. In sum, our study shows that neonatal structural connectivity predicts early motor development after HIE or in subjects with CHD, and regional SLF connectivity is associated with language outcomes. Further research is needed to determine if and how brain networks change over time and whether those changes represent recovery or ongoing dysfunction. This knowledge will directly inform strategies to optimize neurologic functional outcomes after neonatal brain injury.

Prenatal Exposure to Early Life Adversity and Neonatal Brain Volumes at Birth

Importance: Exposure to early life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The extent that prenatal exposure to life adversity alters structure at birth remains poorly understood. Objective: To determine if prenatal exposure to maternal social advantage and psychosocial distress alters global and regional brain volumes and cortical folding in the first weeks of life. Design: A prospective, longitudinal study of sociodemographically-diverse mothers recruited in the first trimester of pregnancy and their infants who underwent brain magnetic resonance imaging scan in the first weeks of life. Setting: Mothers were recruited from local obstetric clinics from 2017-2020. Participants: Of 399 mother-infant dyads prospectively recruited into the parent study, 280 healthy, term-born infants (47% female, mean postmenstrual age at scan 42 weeks) were eligible for inclusion. Exposures: Maternal social advantage and psychosocial distress in pregnancy. Main Measures and Outcomes: Two measures of latent constructs were created using Confirmatory Factor Analyses spanning Maternal Social Advantage (Income to Needs ratio, Area Deprivation Index, Healthy Eating Index, education level, insurance status) and Psychosocial Stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellar, hippocampus, and amygdala volumes were generated using semi-automated age-specific segmentation pipelines. Results: After covariate adjustment and multiple comparisons correction, greater social disadvantage (i.e., lower Advantage values) was associated with reduced cortical gray matter (p=.03), subcortical gray matter (p=.008), and white matter (p=.004) volumes and cortical folding (p=.001). Psychosocial Stress was not related to neonatal brain metrics. While social disadvantage was associated with smaller absolute volumes of the bilateral hippocampi and amygdalae, after correcting for total brain volume, there were no regional effects. Conclusions and Relevance: Prenatal exposure to social disadvantage is associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that the deleterious effects of poverty begin in utero and are evident in the first weeks of life. These findings emphasize that preventative interventions to support fetal brain development should address socioeconomic hardships for expectant parents.

Free Radicals and Neonatal Brain Injury: From Underlying Pathophysiology to Antioxidant Treatment Perspectives

Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles of injury have been identified. The growing evidence on the detrimental effects of free radicals on the brain tissue has led to discover not only potential biomarkers for oxidative damage, but also possible neuroprotective therapeutic approaches targeting oxidative stress. While a more extensive validation of free radical biomarkers is required before considering their use in routine neonatal practice, two important treatments endowed with antioxidant properties, such as therapeutic hypothermia and magnesium sulfate, have become part of the standard of care to reduce the risk of neonatal brain injury, and other promising therapeutic strategies are being tested in clinical trials. The implementation of currently available evidence is crucial to optimize neonatal neuroprotection and to develop individualized diagnostic and therapeutic approaches addressing oxidative brain injury, with the final aim of improving the neurological outcome of this population.

Neurodevelopmental Preparedness for Language in the Neonatal Brain

Neonates show broad-based, universal speech perception abilities, allowing them to acquire any language. Moreover, an increasing body of research shows that prenatal experience with speech, which is a low-pass signal mainly preserving prosody, already shapes those abilities. In this review, we first provide a summary of the empirical evidence available today on newborns’ universal and experience-modulated speech perception abilities. We then interpret these findings in a new framework, focusing on the role of the prenatal prosodic experience in speech perception development. We argue that the chronological sequence of infants’ experience with speech, starting before birth with a low-pass filtered signal and continuing with the full-band signal after birth, sets up the prosodic hierarchy and a cascade of embedded neural oscillations as its brain correlate, laying the foundations for language acquisition. Prosody, constituting infants’ very first experience with language, may thus play a fundamental role in speech perception and language development.

Methods for Monitoring Risk of Hypoxic Damage in Fetal and Neonatal Brains: A Review

Fetal, perinatal, and neonatal asphyxia are vital health issues for the most vulnerable groups in human beings, including fetuses, newborns, and infants. Severe reduction in oxygen and blood supply to the fetal brain can cause hypoxic-ischemic encephalopathy, leading to long-term neurological disorders, including mental impairment and cerebral palsy. Such neurological disorders are major healthcare concerns. Therefore, there has been a continuous effort to develop clinically useful diagnostic tools for accurately and quantitatively measuring and monitoring blood and oxygen supply to the fetal and neonatal brain to avoid severe consequences of asphyxia Hypoxic-Ischemic Encephalopathy (HIE) and Neonatal Encephalopathy (NE). Major diagnostic technologies used for this purpose include fetal heart rate monitoring (FHRM), fetus scalp blood sampling (FBS), ultrasound (US) imaging, magnetic resonance imaging (MRI), x-ray computed tomography (CT), and nuclear medicine. In addition, given the limitations and shortcomings of traditional diagnostic methods, emerging technologies such as near-infrared spectroscopy (NIRS) and photoacoustic (PA) imaging have also been introduced as stand-alone or complementary solutions to address this critical gap in fetal and neonatal care. This review provides a thorough overview of the traditional and emerging technologies for monitoring fetal and neonatal brain oxygenation status and describes their clinical utility, performance, advantages, and disadvantages.

N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice

Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.