Demonstration of stable, long-term operation of a nanosecond pulsed DPSSL at 10 J, 100 Hz.

We report on stable, long-term operation of a diode-pumped solid-state laser (DPSSL) amplifying 15 ns pulses at 1029.5 nm wavelength to 10 J energy at 100 Hz pulse rate, corresponding to 1 kW average power, with 25.4% optical-to-optical efficiency. The laser was operated at this level for over 45 minutes (∼3 · 105 shots) in two separate runs with a rms energy stability of 1%. The laser was also operated at 7 J, 100 Hz for 4 hours (1.44 · 106 shots) with a rms long-term energy stability of 1% and no need for user intervention. To the best of our knowledge, this is the first time that long-term reliable amplification of a kW-class high energy nanosecond pulsed DPSSL at 100 Hz has been demonstrated.

Feasibility of a 2-minute eye-tracking protocol to support the early identification of autism.

We tested the potential for Gazefinder eye-tracking to support early autism identification, including feasible use with infants, and preliminary concurrent validity of trial-level gaze data against clinical assessment scores. We embedded the ~ 2-min 'Scene 1S4' protocol within a comprehensive clinical assessment for 54 consecutively-referred, clinically-indicated infants (prematurity-corrected age 9-14 months). Alongside % tracking rate as a broad indicator of feasible assessment/data capture, we report infant gaze data to pre-specified regions of interest (ROI) across four trial types and associations with scores on established clinical/behavioural tools. Most infants tolerated Gazefinder eye-tracking well, returning high overall % tracking rate. As a group, infants directed more gaze towards social vs. non-social (or more vs. less socially-salient) ROIs within trials. Behavioural autism features were correlated with increased gaze towards non-social/geometry (vs. social/people) scenes. No associations were found for gaze directed to ROIs within other stimulus types. Notably, there were no associations between developmental/cognitive ability or adaptive behaviour with gaze towards any ROI. Gazefinder assessment seems highly feasible with clinically-indicated infants, and the people vs. geometry stimuli show concurrent predictive validity for behavioural autism features. Aggregating data across the ~ 2-min autism identification protocol might plausibly offer greater utility than stimulus-level analysis alone.

Cardiovascular Follow-up of Patients Treated for MIS-C.

OBJECTIVES: To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C). METHODS: Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram. RESULTS: Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups. CONCLUSIONS: The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

Sociodemographic profile associated with congenital heart disease among infants <1 year old.

PURPOSE: Congenital heart disease affects thousands of newborns each year in the United States. Previous United States-based research has explored how sociodemographic factors may impact health outcomes in infants with congenital heart disease; however, their impact on the incidence of congenital heart disease is unclear. We explored the sociodemographic profile related to congenital heart disease to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with congenital heart disease will encourage implementation of potential preventative measures. DESIGN AND METHODS: We conducted a secondary analysis of longitudinally collected data comparing 39 infants with congenital heart disease and 30 healthy controls. We used a questionnaire to collect sociodemographic data. Pearson's chi-square test/Fisher's exact tests analyzed the associations among different sociodemographic factors between infants with congenital heart disease and healthy controls. RESULTS: We found a statistically significant difference in maternal education between our 2 groups of infants (p = 0.004). CONCLUSION: Maternal education was associated with congenital heart disease. Future studies are needed to further characterize sociodemographic factors that may predict and impact the incidence of congenital heart disease and to determine possible interventions that may help decrease health disparities regarding the incidence of congenital heart disease. PRACTICE IMPLICATIONS: Understanding the associations between maternal sociodemographic factors and infant congenital heart disease would allow clinicians to identify mothers at higher risk of having an infant with congenital heart disease.

'It's really important to be collaborating': Experiences of participatory research for Chinese and Vietnamese parents of autistic children.

Background and aims: Participatory research involves academic partners working together with the community that is affected by research to make decisions about that research. Such approaches often result in research that is more respectful of, and responsive to, community preferences - and is vital in the context of autism research with culturally and linguistically diverse (CALD) communities. Whilst participatory approaches are becoming more commonplace within CALD autism research, no studies have explored the experiences of being involved in autism research from the perspectives of CALD community partners over the course of a study. This paper intended to address this gap by reporting on the experiences of CALD parents of autistic children who were community partners in a 1-year Australian research project exploring home-school partnerships for CALD parents of autistic children. We aimed to: (1) report on how parents' involvement in the research process shaped the home-school partnerships study over time and (2) understand their experiences of being community partners on the home-school partnerships project. Methods: Using key principles of participatory approaches, we established Chinese and Vietnamese parent advisory groups to contribute to a project exploring home-school partnerships for parents of autistic children from CALD backgrounds in Australia. Advisory groups included parents of autistic children from Chinese/Vietnamese backgrounds, as well as interpreters, professionals and researchers. We documented how parents' participation as community partners shaped the home-school partnerships study over the course of the project. We also elicited parents' own views and experiences of being community partners through informal, open-ended questions at the beginning and end of the study. Results: We found that parents' input fundamentally shaped the broader home-school partnership study, from meaningful, accurate translation of interview schedules through to making decisions regarding community-specific recommendations and dissemination plans. Parents themselves reported being keen to collaborate and to hear and share opinions for the purpose of the home-school partnership study - although they noted how emotionally difficult sharing their stories could be. While they initially had some concerns about combining being involved as a community partner with their existing responsibilities, ultimately, parents were surprised by the scope of the home-school partnership study and their level of involvement as community partners. Through hearing others' stories and sharing their own in advisory group meetings, parents reported ancillary benefits of their involvement, including increased self-advocacy and well-being. Conclusions: These findings show how research that is conducted in partnership with diverse members of the autism community has the capacity to improve the quality of the research and benefit community partners. Implications: This study clearly documents the benefits and potential challenges of participatory approaches with CALD communities. These findings emphasise to researchers and funders the importance of including extra time and money within budgets in order to produce meaningful research that is respectful and responsive to communities.

Genetic and clinical variables act synergistically to impact neurodevelopmental outcomes in children with single ventricle heart disease.

BACKGROUND: Recent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes remains less understood. Outcomes analyses using genetics are complicated by the intrinsic severity of the CHD lesion and interactions with conditionally dependent clinical variables. METHODS: Bayesian Networks were applied to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD. RESULTS: As isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increase the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables act synergistically to further increase the probability of a low MDI score by 10-fold. The absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increase the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increase the probability of a good outcome by 59-fold. CONCLUSIONS: Our analyses suggest a modest genetic contribution to neurodevelopmental outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.

Single ventricle congenital heart disease is a birth defect. In these children, the heart has only one effective blood-pumping chamber instead of two. Surgery can reroute the blood to use only one chamber, but multiple risk factors influence how well a child develops afterwards. Studying these risk factors can be challenging because they are interconnected, i.e. children with a genetic birth defect may be more likely to have a lower birthweight, and hence more likely to spend longer in hospital after surgery. Here, we used a statistical approach not commonly applied to study congenital heart disease and describe that whether a genetic variant (a small difference in a child's DNA) is important for how a child with single ventricle heart disease develops and grows after surgery depends on the presence of other risk factors.

A pilot study: Comparing a novel noninvasive measure of cerebrovascular stability index with an invasive measure of cerebral autoregulation in neonates with congenital heart disease.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI's correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

Sociodemographic Profile Associated with Congenital Heart Disease among Infants Less than 1 Year Old.

Background: Congenital heart disease (CHD) affects thousands of newborns each year in the United States (US). Infants born with CHD have an increased risk of adverse health outcomes compared to healthy infants. These outcomes include, but are not limited to, neurodevelopmental, surgical, and mortality-related outcomes. Previous US-based research has explored how sociodemographic factors may impact these health outcomes in infants with CHD; however, their impact on the risk of CHD is unclear. This study aims to explore the sociodemographic profile related to CHD to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with CHD will encourage policy change and the implementation of preventative measures. Methods: This study is a secondary analysis of longitudinally collected data. We compared infants with CHD and healthy controls. We used a questionnaire to collect sociodemographic data. Pearson's chi-square test/Fisher's exact tests analyzed the associations among different sociodemographic factors between infants with CHD and healthy controls. Results: We obtained sociodemographic factors from 30 healthy control infants and 39 infants with CHD. We found a statistically significant difference in maternal education between our 2 groups of infants (p=0.004). Conclusion: Maternal education is associated with CHD. Future studies are needed to further characterize sociodemographic factors that may predict and impact the risk of CHD and to determine possible interventions that may help decrease health disparities regarding the risk of CHD.

'Somali parents feel like they're on the outer': Somali mothers' experiences of parent-teacher relationships for their autistic children.

LAY ABSTRACT: Good relationships between parents and schools can improve autistic children's school success. There are many reasons why families from different cultural backgrounds find it harder to develop good relationships with schools, such as language barriers, discrimination and unfamiliarity with education systems. We know little about what 'good relationships' look like for these families. Here, we worked with a team of autistic and non-autistic researchers as well as an Advisory Group of Somali parents to conduct interviews with 15 Somali mothers of kindergarten and school-age autistic children. We asked mothers about their experiences of their child's education, communication with teachers and what a good relationship with schools would look like. We also asked how they felt the Somali community understood autism. We looked for common things that mothers said. We found that mothers were very proud of their children. They had high expectations, particularly about what children could do by themselves. Mothers found it frustrating that teachers had low expectations, that schools were not good at communicating with them and that autism-specific skills and experience were uncommon in schools. They also reported racist attitudes towards their children. Mothers experienced stigma and lacked resources, but support was gained from their daughters and their religion. Mothers themselves were proactively increasing community awareness and knowledge about autism in the hope that they and their autistic children would be valued and better supported. Our work has implications for how teachers and schools can work together with Somali parents to forge better futures for autistic children.

The Utility of Natural Language Samples for Assessing Communication and Language in Infants Referred with Early Signs of Autism.

Natural Language Sampling (NLS) offers clear potential for communication and language assessment, where other data might be difficult to interpret. We leveraged existing primary data for 18-month-olds showing early signs of autism, to examine the reliability and concurrent construct validity of NLS-derived measures coded from video-of child language, parent linguistic input, and dyadic balance of communicative interaction-against standardised assessment scores. Using Systematic Analysis of Language Transcripts (SALT) software and coding conventions, masked coders achieved good-to-excellent inter-rater agreement across all measures. Associations across concurrent measures of analogous constructs suggested strong validity of NLS applied to 6-min video clips. NLS offers benefits of feasibility and adaptability for validly quantifying emerging skills, and potential for standardisation for clinical use and rigorous research design.

Parental Imitations and Expansions of Child Language Predict Later Language Outcomes of Autistic Preschoolers.

Both the amount and responsiveness of adult language input contribute to the language development of autistic and non-autistic children. From parent-child interaction footage, we measured the amount of adult language input, overall parent responsiveness, and six discrete parent responsive behaviours (imitations, expansions, open-ended questions, yes/no questions, comments and acknowledgements) to explore which types of responsiveness predicted autistic preschoolers' language five months later, after controlling for adult language input. We found expansions and particularly imitations to be more important for later language than overall responsiveness. This study emphasises the need to capture what exactly about parent language input influences child language acquisition, and adds to the evidence that imitating and expanding early language might be particularly beneficial for autistic preschoolers.

"They Were Saying That I Was a Typical Chinese Mum" : Chinese Parents' Experiences of Parent-Teacher Partnerships for Their Autistic Children.

Effective parent-teacher partnerships improve outcomes for autistic students. Yet, we know little about what effective partnerships look like for parents of autistic children from different backgrounds. We conducted interviews with 17 Chinese parents of autistic children attending Australian kindergartens/schools to understand their experiences. Parents appreciated the acceptance, opportunities and supports they received in Australia. They had high expectations of children; expectations not often shared by educators. Parents were respectful of teachers' expertise and polite and undemanding in interactions. Nevertheless, parents were frustrated by inconsistent teaching quality and inadequate communication. Navigating systems was also challenging and parents faced discrimination from teachers and their community. Recommendations include fostering open home-school communication, proactively seeking parents' expertise about children and explicitly scaffolding parents' self-advocacy.

Caregiver sensitivity predicts infant language use, and infant language complexity predicts caregiver language complexity, in the context of possible emerging autism.

While theory supports bidirectional effects between caregiver sensitivity and language use, and infant language acquisition-both caregiver-to-infant and also infant-to-caregiver effects-empirical research has chiefly explored the former unidirectional path. In the context of infants showing early signs of autism, we investigated prospective bidirectional associations with 6-min free-play interaction samples collected for 103 caregivers and their infants (mean age 12-months; and followed up 6-months later). We anticipated that measures of caregiver sensitivity/language input and infant language would show within-domain temporal stability/continuity, but also that there would be predictive associations from earlier caregiver input to subsequent child language, and vice versa. Caregiver sensitive responsiveness (from the Manchester Assessment of Caregiver-Infant interaction [MACI]) predicted subsequent infant word tokens (i.e., amount of language, coded following the Systematic Analysis of Language Transcripts [SALT]). Further, earlier infant Mean Length of Utterance (MLU; reflecting language complexity, also derived from SALT coding) predicted later caregiver MLU, even when controlling for variability in infant ages and clear within-domain temporal stability/continuity in key measures (i.e., caregiver sensitive responsiveness and infant word tokens; and infant and caregiver MLU). These data add empirical support to theorization on how caregiver input can be both supportive of, and potentially influenced by, infant capacities, when infants have social-communication differences and/or communication/language delays suggestive of possible emerging autism.

Clinical factors associated with microstructural connectome related brain dysmaturation in term neonates with congenital heart disease.

Objective: Term congenital heart disease (CHD) neonates display abnormalities of brain structure and maturation, which are possibly related to underlying patient factors, abnormal physiology and perioperative insults. Our primary goal was to delineate associations between clinical factors and postnatal brain microstructure in term CHD neonates using diffusion tensor imaging (DTI) magnetic resonance (MR) acquisition combined with complementary data-driven connectome and seed-based tractography quantitative analyses. Our secondary goal was to delineate associations between mild dysplastic structural brain abnormalities and connectome and seed-base tractography quantitative analyses. These mild dysplastic structural abnormalities have been derived from prior human infant CHD MR studies and neonatal mouse models of CHD that were collectively used to calculate to calculate a brain dysplasia score (BDS) that included assessment of subcortical structures including the olfactory bulb, the cerebellum and the hippocampus. Methods: Neonates undergoing cardiac surgery for CHD were prospectively recruited from two large centers. Both pre- and postoperative MR brain scans were obtained. DTI in 42 directions was segmented into 90 regions using a neonatal brain template and three weighted methods. Clinical data collection included 18 patient-specific and 9 preoperative variables associated with preoperative scan and 6 intraoperative (e.g., cardiopulmonary bypass and deep hypothermic circulatory arrest times) and 12 postoperative variables associated with postoperative scan. We compared patient specific and preoperative clinical factors to network topology and tractography alterations on a preoperative neonatal brain MRI, and intra and postoperative clinical factors to network topology alterations on postoperative neonatal brain MRI. A composite BDS was created to score abnormal findings involving the cerebellar hemispheres and vermis, supratentorial extra-axial fluid, olfactory bulbs and sulci, hippocampus, choroid plexus, corpus callosum, and brainstem. The neuroimaging outcomes of this study included (1) connectome metrics: cost (number of connections) and global/nodal efficiency (network integration); (2) seed based tractography methods of fractional anisotropy (FA), radial diffusivity, and axial diffusivity. Statistics consisted of multiple regression with false discovery rate correction (FDR) comparing the clinical risk factors and BDS (including subcortical components) as predictors/exposures and the global connectome metrics, nodal efficiency, and seed based- tractography (FA, radial diffusivity, and axial diffusivity) as neuroimaging outcome measures. Results: A total of 133 term neonates with complex CHD were prospectively enrolled and 110 had analyzable DTI. Multiple patient-specific factors including d-transposition of the great arteries (d-TGA) physiology and severity of impairment of fetal cerebral substrate delivery (i.e., how much the CHD lesion alters typical fetal circulation such that the highest oxygen and nutrient rich blood from the placenta are not directed toward the fetal brain) were predictive of preoperative reduced cost (p < 0.0073) and reduced global/nodal efficiency (p < 0.03). Cardiopulmonary bypass time predicted postoperative reduced cost (p < 0.04) and multiple postoperative factors [extracorporeal membrane oxygenation (ECMO), seizures and cardiopulmonary resuscitation (CPR)] were predictive of postoperative reduced cost and reduced global/nodal efficiency (p < 0.05). Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. Total BDS was not predictive of brain network topology. However, key subcortical components of the BDS score did predict key global and nodal network topology: abnormalities of the cerebellum predicted reduced cost (p < 0.0417) and of the hippocampus predicted reduced global efficiency (p < 0.0126). All three subcortical structures predicted unique alterations of nodal efficiency (p < 0.05), including hippocampal abnormalities predicting widespread reduced nodal efficiency in all lobes of the brain, cerebellar abnormalities predicting increased prefrontal nodal efficiency, and olfactory bulb abnormalities predicting posterior parietal-occipital nodal efficiency. Conclusion: Patient-specific (d-TGA anatomy, preoperative impairment of fetal cerebral substrate delivery) and postoperative (e.g., seizures, need for ECMO, or CPR) clinical factors were most predictive of diffuse postnatal microstructural dysmaturation in term CHD neonates. Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. In contrast, subcortical components (cerebellum, hippocampus, olfactory) of a structurally based BDS (derived from CHD mouse mutants), predicted more localized and regional postnatal microstructural differences. Collectively, these findings suggest that brain DTI connectome and seed-based tractography are complementary techniques which may facilitate deciphering the mechanistic relative contribution of clinical and genetic risk factors related to poor neurodevelopmental outcomes in CHD.

Associations between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease.

The relationship between maternal risk factors (MRFs) (particularly pre-gravid obesity, diabetes, and hypertension) and congenital heart disease (CHD) to placental and fetal brain outcomes is poorly understood. Here, we tested the hypothesis that MRF and CHD would be associated with reduced intrinsic placental and fetal brain function using a novel non-invasive technique. Pregnant participants with and without MRF and fetal CHD were prospectively recruited and underwent feto-placental MRI. Using intrinsic properties of blood oxygen level dependent imaging (BOLD) we quantified spatiotemporal variance of placenta and fetal brain. MRFs and CHD were correlated with functional characteristics of the placenta and fetal brain. Co-morbid MRF (hypertension, diabetes, and obesity) reduced spatiotemporal functional variance of placenta and fetal brain (p < 0.05). CHD predicted reduced fetal brain temporal variance compared to non-CHD (p < 0.05). The presence of both MRF and CHD was associated with reduced intrinsic pBOLD temporal variance (p = 0.047). There were no significant interactions of MRFs and CHD status on either temporal or spatial variance of intrinsic brain BOLD. MRF and CHD reduced functional characteristic of placenta and brain in fetuses. MRF modification and management during pregnancy may have the potential to not only provide additional risk stratification but may also improve neurodevelopmental outcomes.

Harmonization of Multi-Center Diffusion Tensor Tractography in Neonates with Congenital Heart Disease: Optimizing Post-Processing and Application of ComBat.

Advanced brain imaging of neonatal macrostructure and microstructure, which has prognosticating importance, is more frequently being incorporated into multi-center trials of neonatal neuroprotection. Multicenter neuroimaging studies, designed to overcome small sample sized clinical cohorts, are essential but lead to increased technical variability. Few harmonization techniques have been developed for neonatal brain microstructural (diffusion tensor) analysis. The work presented here aims to remedy two common problems that exist with the current state of the art approaches: 1) variance in scanner and protocol in data collection can limit the researcher's ability to harmonize data acquired under different conditions or using different clinical populations. 2) The general lack of objective guidelines for dealing with anatomically abnormal anatomy and pathology. Often, subjects are excluded due to subjective criteria, or due to pathology that could be informative to the final analysis, leading to the loss of reproducibility and statistical power. This proves to be a barrier in the analysis of large multi-center studies and is a particularly salient problem given the relative scarcity of neonatal imaging data. We provide an objective, data-driven, and semi-automated neonatal processing pipeline designed to harmonize compartmentalized variant data acquired under different parameters. This is done by first implementing a search space reduction step of extracting the along-tract diffusivity values along each tract of interest, rather than performing whole-brain harmonization. This is followed by a data-driven outlier detection step, with the purpose of removing unwanted noise and outliers from the final harmonization. We then use an empirical Bayes harmonization algorithm performed at the along-tract level, with the output being a lower dimensional space but still spatially informative. After applying our pipeline to this large multi-site dataset of neonates and infants with congenital heart disease (n= 398 subjects recruited across 4 centers, with a total of n=763 MRI pre-operative/post-operative time points), we show that infants with single ventricle cardiac physiology demonstrate greater white matter microstructural alterations compared to infants with bi-ventricular heart disease, supporting what has previously been shown in literature. Our method is an open-source pipeline for delineating white matter tracts in subject space but provides the necessary modular components for performing atlas space analysis. As such, we validate and introduce Diffusion Imaging of Neonates by Group Organization (DINGO), a high-level, semi-automated framework that can facilitate harmonization of subject-space tractography generated from diffusion tensor imaging acquired across varying scanners, institutions, and clinical populations. Datasets acquired using varying protocols or cohorts are compartmentalized into subsets, where a cohort-specific template is generated, allowing for the propagation of the tractography mask set with higher spatial specificity. Taken together, this pipeline can reduce multi-scanner technical variability which can confound important biological variability in relation to neonatal brain microstructure.

Impaired Neurovascular Function Underlies Poor Neurocognitive Outcomes and Is Associated with Nitric Oxide Bioavailability in Congenital Heart Disease.

We use a non-invasive MRI proxy of neurovascular function (pnvf) to assess the ability of the vasculature to supply baseline metabolic demand, to compare pediatric and young adult congenital heart disease (CHD) patients to normal referents and relate the proxy to neurocognitive outcomes and nitric oxide bioavailability. In a prospective single-center study, resting-state blood-oxygen-level-dependent (BOLD) and arterial spin labeling (ASL) MRI scans were successfully obtained from 24 CHD patients (age = 15.4 ± 4.06 years) and 63 normal referents (age = 14.1 ± 3.49) years. Pnvf was computed on a voxelwise basis as the negative of the ratio of functional connectivity strength (FCS) estimated from the resting-state BOLD acquisition to regional cerebral blood flow (rCBF) as estimated from the ASL acquisition. Pnvf was used to predict end-tidal CO2 (PETCO2) levels and compared to those estimated from the BOLD data. Nitric oxide availability was obtained via nasal measurements (nNO). Pnvf was compared on a voxelwise basis between CHD patients and normal referents and correlated with nitric oxide availability and neurocognitive outcomes as assessed via the NIH Toolbox. Pnvf was shown as highly predictive of PETCO2 using theoretical modeling. Pnvf was found to be significantly reduced in CHD patients in default mode network (DMN, comprising the ventromedial prefrontal cortex and posterior cingulate/precuneus), salience network (SN, comprising the insula and dorsal anterior cingulate), and central executive network (CEN, comprising posterior parietal and dorsolateral prefrontal cortex) regions with similar findings noted in single cardiac ventricle patients. Positive correlations of Pnvf in these brain regions, as well as the hippocampus, were found with neurocognitive outcomes. Similarly, positive correlations between Pnvf and nitric oxide availability were found in frontal DMN and CEN regions, with particularly strong correlations in subcortical regions (putamen). Reduced Pnvf in CHD patients was found to be mediated by nNO. Mediation analyses further supported that reduced Pnvf in these regions underlies worse neurocognitive outcome in CHD patients and is associated with nitric oxide bioavailability. Impaired neuro-vascular function, which may be non-invasively estimated via combined arterial-spin label and BOLD MR imaging, is a nitric oxide bioavailability dependent factor implicated in adverse neurocognitive outcomes in pediatric and young adult CHD.

Factor Analysis of the Einstein Neonatal Neurobehavioral Assessment Scale in Infants with Congenital Heart Disease and Healthy Controls.

Background: Administration of the Einstein Neonatal Neurobehavioral Assessment Scale (ENNAS) can be time-consuming, and items can be highly correlated. We aimed to determine: (1) its factor analytic structure; (2) the validity of the factor structure; and (3) the associations of physiologic measures with factor scores. Methods: A factor analysis reduced 21 ENNAS items into 5 factors in 57 congenital heart disease (CHD) and 35 healthy infants. Multiple linear regressions examined the association of factor scores with group, gestational age, and physiologic variables. Results: 5-factor solution: 1 (Orienting Reflex), 2 (Extensor Axial Tone), 3 (Primitive Reflexes), 4 (Flexor Tone), 5 (Reflexive Tone Around Extremity Joints). Moderate to strong evidence supported: face, discriminant, and construct validity of these factors, with Factor 2 having the strongest. Conclusions: Components of Factor 2 may provide similar information about neonatal development, thus reducing the time for and burden of administration for researchers and clinicians.