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BACKGROUND: Congenital heart disease (CHD) has been linked to impaired placental and fetal brain development. Assessing the placenta and fetal brain in parallel may help further our understanding of the relationship between development of these organs. HYPOTHESIS: 1) Placental and fetal brain oxygenation are correlated, 2) oxygenation in these organs is reduced in CHD compared to healthy controls, and 3) placental structure is altered in CHD. STUDY TYPE: Retrospective case-control. POPULATION: Fifty-one human fetuses with CHD (32 male; median [IQR] gestational age [GA] = 32.0 [30.9-32.9] weeks) and 30 from uncomplicated pregnancies with normal birth outcomes (18 male; median [IQR] GA = 34.5 [31.9-36.7] weeks). FIELD STRENGTH/SEQUENCE: 1.5 T single-shot multi-echo-gradient-echo echo-planar imaging. ASSESSMENT: Masking was performed using an automated nnUnet model. Mean brain and placental T2* and quantitative measures of placental texture, volume, and morphology were calculated. STATISTICAL TESTS: Spearman's correlation coefficient for determining the association between brain and placental T2*, and between brain and placental characteristics with GA. P-values for comparing brain T2*, placenta T2*, and placental characteristics between groups derived from ANOVA. Significance level P < 0.05. RESULTS: There was a significant positive association between placental and fetal brain T2* (â´ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* â´ = -0.65; fetal brain T2* â´ = -0.32). Both placental and fetal brain T2* values were significantly reduced in CHD, after adjusting for GA (placental T2*: control = 97 [±24] msec, CHD = 83 [±23] msec; brain T2*: control = 218 [±26] msec, CHD = 202 [±25] msec). Placental texture and morphology were also significantly altered in CHD (Texture: control = 0.84 [0.83-0.87], CHD = 0.80 [0.78-0.84]; Morphology: control = 9.9 [±2.2], CHD = 10.8 [±2.0]). For all fetuses, there was a significant positive association between placental T2* and placental texture (â´ = 0.46). CONCLUSION: Placental and fetal brain T2* values are associated in healthy fetuses and those with CHD. Placental and fetal brain oxygenation are reduced in CHD. Placental appearance is significantly altered in CHD and shows associations with placental oxygenation, suggesting altered placental development and function may be related. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.
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The complex, tightly regulated process of prenatal brain development may be adversely affected by "everyday exposures" such as stress and environmental pollutants. Researchers are only just beginning to understand the neural sequelae of such exposures, with advances in fetal and neonatal neuroimaging elucidating structural, microstructural, and functional correlates in the developing brain. This narrative review discusses the wide-ranging literature investigating the influence of parental stress on fetal and neonatal brain development as well as emerging literature assessing the impact of exposure to environmental toxicants such as lead and air pollution. These 'everyday exposures' can co-occur with other stressors such as social and financial deprivation, and therefore we include a brief discussion of neuroimaging studies assessing the effect of social disadvantage. Increased exposure to prenatal stressors is associated with alterations in the brain structure, microstructure and function, with some evidence these associations are moderated by factors such as infant sex. However, most studies examine only single exposures and the literature on the relationship between in utero exposure to pollutants and fetal or neonatal brain development is sparse. Large cohort studies are required that include evaluation of multiple co-occurring exposures in order to fully characterize their impact on early brain development. IMPACT: Increased prenatal exposure to parental stress and is associated with altered functional, macro and microstructural fetal and neonatal brain development. Exposure to air pollution and lead may also alter brain development in the fetal and neonatal period. Further research is needed to investigate the effect of multiple co-occurring exposures, including stress, environmental toxicants, and socioeconomic deprivation on early brain development.
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World Health Organisation data suggest that up to 99% of the global population are exposed to air pollutants above recommended levels. Impacts to health range from increased risk of stroke and cardiovascular disease to chronic respiratory conditions, and air pollution may contribute to over 7 million premature deaths a year. Additionally, mounting evidence suggests that in utero or early life exposure to particulate matter (PM) in ambient air pollution increases the risk of neurodevelopmental impairment with obvious lifelong consequences. Identifying brain-specific cellular targets of PM is vital for determining its long-term consequences. We previously established that microglial-like BV2 cells were particularly sensitive to urban (U)PM-induced damage including reactive oxygen species production, which was abrogated by a mitochondrially targeted antioxidant. Here we extend those studies to find that UPM treatment causes a rapid impairment of mitochondrial function and increased mitochondrial fragmentation. However, there is a subsequent restoration of mitochondrial and therefore cell health occurring concomitantly with upregulated measures of mitochondrial biogenesis and mitochondrial load. Our data highlight that protecting mitochondrial function may represent a valuable mechanism to offset the effects of UPM exposure in the neonatal brain. KEY POINTS: Air pollution represents a growing risk to long-term health especially in early life, and the CNS is emerging a target for airborne particulate matter (PM). We previously showed that microglial-like BV2 cells were vulnerable to urban (U)PM exposure, which impaired cell survival and promoted reactive oxygen species production. Here we find that, following UPM exposure, BV2 mitochondrial membrane potential is rapidly reduced, concomitant with decreased cellular bioenergetics and increased mitochondrial fission. However, markers of mitochondrial biogenesis and mitochondrial mass are subsequently induced, which may represent a cellular mitigation strategy. As mitochondria are more vulnerable in the developing brain, exposure to air pollution may represent a greater risk to lifelong health in this cohort; conversely, promoting mitochondrial integrity may offset these risks.
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Microglía , Mitocondrias , Dinámicas Mitocondriales , Material Particulado , Material Particulado/toxicidad , Animales , Ratones , Dinámicas Mitocondriales/efectos de los fármacos , Línea Celular , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Biogénesis de Organelos , Contaminantes Atmosféricos/toxicidad , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.
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Cardiopatías Congénitas , Imagen por Resonancia Magnética , Placenta , Placentación , Humanos , Femenino , Embarazo , Cardiopatías Congénitas/diagnóstico por imagen , Adulto , Placenta/diagnóstico por imagen , Placenta/patología , Imagen por Resonancia Magnética/métodos , Estudios de Casos y ControlesRESUMEN
Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.
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Trastorno Autístico , Recien Nacido Prematuro , Preescolar , Lactante , Adulto , Humanos , Recién Nacido , Encéfalo/patología , Mapeo Encefálico , Imagen por Resonancia MagnéticaRESUMEN
Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR<0.001), with changes most evident after 30 weeks gestation. A Significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR=0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.
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OBJECTIVE: To assess the relationships between (1) environmental and demographic factors and executive function (EF) in preschool children with congenital heart disease (CHD) and controls and (2) clinical and surgical risk factors and EF in preschool children with CHD. STUDY DESIGN: At 4-6 years of age, parents of children with CHD (n = 51) and controls (n = 124) completed the Behavior Rating Inventory of Executive Function, Preschool Version questionnaire and the Cognitively Stimulating Parenting Scale (CSPS). Multivariable general linear modeling assessed the relationship between Behavior Rating Inventory of Executive Function, Preschool Version composite scores (Inhibitory Self-Control Index [ISCI], Flexibility Index [FI], and Emergent Metacognition Index [EMI]) and group (CHD/control), sex, age at assessment, gestational age, Index of Multiple Deprivation, and CSPS scores. The relationships between CHD type, surgical factors, and brain magnetic resonance imaging injury rating and ISCI, FI, and EMI scores were assessed. RESULTS: The presence of CHD, age at assessment, sex, and Index of Multiple Deprivation were not associated with EF scores. Lower gestational age was associated with greater ISCI and FI scores, and age at assessment was associated with lower FI scores. Group significantly moderated the relationship between CSPS and EF, such that CSPS significantly predicted EF in children with CHD (ISCI: P = .0004; FI: P = .0015; EMI: P = .0004) but not controls (ISCI: P = .2727; FI: P = .6185; EMI: P = .3332). There were no significant relationships between EF scores and surgical factors, CHD type, or brain magnetic resonance imaging injury rating. CONCLUSIONS: Supporting parents to provide a cognitively stimulating home environment may improve EF in children with CHD. The home and parenting environment should be considered when designing intervention studies aimed at improving EF in this patient group.
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Función Ejecutiva , Cardiopatías Congénitas , Humanos , Preescolar , Ambiente en el Hogar , Responsabilidad Parental , Padres , Cardiopatías Congénitas/complicacionesRESUMEN
OBJECTIVE: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD). STUDY DESIGN: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up. RESULTS: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, ß = -0.50). SES was independently associated with cognitive outcome (P < .001, ß = 0.26), and LOS with motor outcome (P < .001, ß = -0.35). CONCLUSION: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors.
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Lesiones Encefálicas , Cardiopatías Congénitas , Lactante , Humanos , Preescolar , Encéfalo/patología , Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/complicaciones , Imagen por Resonancia Magnética , Factores de RiesgoRESUMEN
Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3-53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas' and South London & Maudsley NHS Foundation Trusts and King's College London.
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INTRODUCTION: In-vivo measurements of placental structure and function have the potential to improve prediction, diagnosis, and treatment planning for a wide range of pregnancy complications, such as fetal growth restriction and pre-eclampsia, and hence inform clinical decision making, ultimately improving patient outcomes. MRI is emerging as a technique with increased sensitivity to placental structure and function compared to the current clinical standard, ultrasound. METHODS: We demonstrate and evaluate a combined diffusion-relaxation MRI acquisition and analysis pipeline on a sizable cohort of 78 normal pregnancies with gestational ages ranging from 15 + 5 to 38 + 4 weeks. Our acquisition comprises a combined T2*-diffusion MRI acquisition sequence - which is simultaneously sensitive to oxygenation, microstructure and microcirculation. We analyse our scans with a data-driven unsupervised machine learning technique, InSpect, that parsimoniously identifies distinct components in the data. RESULTS: We identify and map seven potential placental microenvironments and reveal detailed insights into multiple microstructural and microcirculatory features of the placenta, and assess their trends across gestation. DISCUSSION: By demonstrating direct observation of micro-scale placental structure and function, and revealing clear trends across pregnancy, our work contributes towards the development of robust imaging biomarkers for pregnancy complications and the ultimate goal of a normative model of placental development.
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Imagen de Difusión por Resonancia Magnética , Placenta , Embarazo , Humanos , Femenino , Placenta/diagnóstico por imagen , Microcirculación , Retardo del Crecimiento Fetal , Imagen por Resonancia Magnética/métodos , PlacentaciónRESUMEN
BACKGROUND: Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear. PURPOSE: To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes. STUDY TYPE: Retrospective case-control study. POPULATION: Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery. FIELD STRENGTH/SEQUENCE: T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner. ASSESSMENT: Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups. STATISTICAL TESTS: ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR -values <0.05 were considered statistically significant. RESULTS: Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios. DATA CONCLUSION: Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.
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Background Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. Methods and Results A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. Z-scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of Z-score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate P<0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate P=0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate P=0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate P<0.027). Conclusions Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short- and long-term hypoxic injury.
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Encéfalo , Cardiopatías Congénitas , Humanos , Lactante , Encéfalo/patología , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Imagen por Resonancia Magnética/métodos , Factores de RiesgoRESUMEN
Fetal MRI is widely used for quantitative brain volumetry studies. However, currently, there is a lack of universally accepted protocols for fetal brain parcellation and segmentation. Published clinical studies tend to use different segmentation approaches that also reportedly require significant amounts of time-consuming manual refinement. In this work, we propose to address this challenge by developing a new robust deep learning-based fetal brain segmentation pipeline for 3D T2w motion corrected brain images. At first, we defined a new refined brain tissue parcellation protocol with 19 regions-of-interest using the new fetal brain MRI atlas from the Developing Human Connectome Project. This protocol design was based on evidence from histological brain atlases, clear visibility of the structures in individual subject 3D T2w images and the clinical relevance to quantitative studies. It was then used as a basis for developing an automated deep learning brain tissue parcellation pipeline trained on 360 fetal MRI datasets with different acquisition parameters using semi-supervised approach with manually refined labels propagated from the atlas. The pipeline demonstrated robust performance for different acquisition protocols and GA ranges. Analysis of tissue volumetry for 390 normal participants (21-38 weeks gestational age range), scanned with three different acquisition protocols, did not reveal significant differences for major structures in the growth charts. Only minor errors were present in < 15% of cases thus significantly reducing the need for manual refinement. In addition, quantitative comparison between 65 fetuses with ventriculomegaly and 60 normal control cases were in agreement with the findings reported in our earlier work based on manual segmentations. These preliminary results support the feasibility of the proposed atlas-based deep learning approach for large-scale volumetric analysis. The created fetal brain volumetry centiles and a docker with the proposed pipeline are publicly available online at https://hub.docker.com/r/fetalsvrtk/segmentation (tag brain_bounti_tissue).
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Introduction: Compared to full-term (FT) born peers, children who were born very preterm (VPT; <32 weeks' gestation) are likely to display more cognitive and behavioral difficulties, including inattention, anxiety and socio-communication problems. In the published literature, such difficulties tend to be studied independently, thus failing to account for how different aspects of child development interact. The current study aimed to investigate children's cognitive and behavioral outcomes as interconnected, dynamically related facets of development that influence one another. Methods: Participants were 93 VPT and 55 FT children (median age 8.79 years). IQ was evaluated with the Wechsler Intelligence Scale for Children-4th edition (WISC-IV), autism spectrum condition (ASC) traits with the social responsiveness scale-2nd edition (SRS-2), behavioral and emotional problems with the strengths and difficulties questionnaire (SDQ), temperament with the temperament in middle childhood questionnaire (TMCQ) and executive function with the behavior rating inventory of executive functioning (BRIEF-2). Outcome measures were studied in VPT and FT children using Network Analysis, a method that graphically represents partial correlations between variables and yields information on each variable's propensity to form a bridge between other variables. Results: VPT and FT children exhibited marked topological differences. Bridges (i.e., the variables most connected to others) in the VPT group network were: conduct problems and difficulties with organizing and ordering their environment. In the FT group network, the most important bridges were: difficulties with initiating a task or activity and prosocial behaviors, and greater emotional problems, such as lower mood. Discussion: These findings highlight the importance of targeting different aspects of development to support VPT and FT children in person-based interventions.
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Preterm birth results in premature exposure of the brain to the extrauterine environment during a critical period of neurodevelopment. Consequently, infants born preterm are at a heightened risk of adverse behavioural outcomes in later life. We characterise longitudinal development of neonatal regional brain volume and functional connectivity in the first weeks following preterm birth, sociodemographic factors, and their respective relationships to psychomotor outcomes and psychopathology in toddlerhood. We study 121 infants born preterm who underwent magnetic resonance imaging shortly after birth, at term-equivalent age, or both. Longitudinal regional brain volume and functional connectivity were modelled as a function of psychopathology and psychomotor outcomes at 18 months. Better psychomotor functioning in toddlerhood was associated with greater relative right cerebellar volume and a more rapid decrease over time of sensorimotor degree centrality in the neonatal period. In contrast, increased 18-month psychopathology was associated with a more rapid decrease in relative regional subcortical volume. Furthermore, while socio-economic deprivation was related to both psychopathology and psychomotor outcomes, cognitively stimulating parenting predicted psychopathology only. Our study highlights the importance of longitudinal imaging to better predict toddler outcomes following preterm birth, as well as disparate environmental influences on separable facets of behavioural development in this population.
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Recien Nacido Prematuro , Nacimiento Prematuro , Femenino , Recién Nacido , Lactante , Humanos , Nacimiento Prematuro/patología , Encéfalo , Imagen por Resonancia Magnética/métodos , DemografíaRESUMEN
PURPOSE: Studying placental development informs when development is abnormal. Most placental MRI studies are cross-sectional and do not study the extent of individual variability throughout pregnancy. We aimed to explore how diffusion MRI measures of placental function and microstructure vary in individual healthy pregnancies throughout gestation. METHODS: Seventy-nine pregnant, low-risk participants (17 scanned twice and 62 scanned once) were included. T2 -weighted anatomical imaging and a combined multi-echo spin-echo diffusion-weighted sequence were acquired at 3 T. Combined diffusion-relaxometry models were performed using both a T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -ADC and a bicompartmental T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -intravoxel-incoherent-motion ( T 2 * IVIM $$ {\mathrm{T}}_2^{\ast}\;\mathrm{IVIM} $$ ) model fit. RESULTS: There was a significant decline in placental T 2 * $$ {\mathrm{T}}_2^{\ast } $$ and ADC (both P < 0.01) over gestation. These declines are consistent in individuals for T 2 * $$ {\mathrm{T}}_2^{\ast } $$ (covariance = -0.47), but not ADC (covariance = -1.04). The T 2 * IVIM $$ {\mathrm{T}}_2^{\ast}\;\mathrm{IVIM} $$ model identified a consistent decline in individuals over gestation in T 2 * $$ {\mathrm{T}}_2^{\ast } $$ from both the perfusing and diffusing placental compartments, but not in ADC values from either. The placental perfusing compartment fraction increased over gestation (P = 0.0017), but this increase was not consistent in individuals (covariance = 2.57). CONCLUSION: Whole placental T 2 * $$ {\mathrm{T}}_2^{\ast } $$ and ADC values decrease over gestation, although only T 2 * $$ {\mathrm{T}}_2^{\ast } $$ values showed consistent trends within subjects. There was minimal individual variation in rates of change of T 2 * $$ {\mathrm{T}}_2^{\ast } $$ values from perfusing and diffusing placental compartments, whereas trends in ADC values from these compartments were less consistent. These findings probably relate to the increased complexity of the bicompartmental T 2 * IVIM $$ {\mathrm{T}}_2^{\ast}\;\mathrm{IVIM} $$ model, and differences in how different placental regions evolve at a microstructural level. These placental MRI metrics from low-risk pregnancies provide a useful benchmark for clinical cohorts.
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Benchmarking , Placenta , Humanos , Femenino , Embarazo , Placenta/diagnóstico por imagen , Estudios Transversales , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Movimiento (Física)RESUMEN
Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.
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Síndrome de Down , Sustancia Blanca , Recién Nacido , Niño , Humanos , Síndrome de Down/diagnóstico por imagen , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: Prenatal exposure to air pollution is associated with adverse neurologic consequences in childhood. However, the relationship between in utero exposure to air pollution and neonatal brain development is unclear. METHODS: We modelled maternal exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) at postcode level between date of conception to date of birth and studied the effect of prenatal air pollution exposure on neonatal brain morphology in 469 (207 male) healthy neonates, with gestational age of ≥36 weeks. Infants underwent MR neuroimaging at 3 Tesla at 41.29 (36.71-45.14) weeks post-menstrual age (PMA) as part of the developing human connectome project (dHCP). Single pollutant linear regression and canonical correlation analysis (CCA) were performed to assess the relationship between air pollution and brain morphology, adjusting for confounders and correcting for false discovery rate. RESULTS: Higher exposure to PM10 and lower exposure to NO2 was strongly canonically correlated to a larger relative ventricular volume, and moderately associated with larger relative size of the cerebellum. Modest associations were detected with higher exposure to PM10 and lower exposure to NO2 and smaller relative cortical grey matter and amygdala and hippocampus, and larger relaive brainstem and extracerebral CSF volume. No associations were found with white matter or deep grey nuclei volume. CONCLUSIONS: Our findings show that prenatal exposure to air pollution is associated with altered brain morphometry in the neonatal period, albeit with opposing results for NO2 and PM10. This finding provides further evidence that reducing levels of maternal exposure to particulate matter during pregnancy should be a public health priority and highlights the importance of understanding the impacts of air pollution on this critical development window.
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Contaminación del Aire , Encéfalo , Exposición Materna , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/estadística & datos numéricos , Encéfalo/crecimiento & desarrollo , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Exposición Materna/estadística & datos numéricosRESUMEN
Very preterm birth (VPT; ≤32 weeks' gestation) is associated with altered brain development and cognitive and behavioral difficulties across the lifespan. However, heterogeneity in outcomes among individuals born VPT makes it challenging to identify those most vulnerable to neurodevelopmental sequelae. Here, we aimed to stratify VPT children into distinct behavioral subgroups and explore between-subgroup differences in neonatal brain structure and function. 198 VPT children (98 females) previously enrolled in the Evaluation of Preterm Imaging Study (EudraCT 2009-011602-42) underwent Magnetic Resonance Imaging at term-equivalent age and neuropsychological assessments at 4-7 years. Using an integrative clustering approach, we combined neonatal socio-demographic, clinical factors and childhood socio-emotional and executive function outcomes, to identify distinct subgroups of children based on their similarity profiles in a multidimensional space. We characterized resultant subgroups using domain-specific outcomes (temperament, psychopathology, IQ and cognitively stimulating home environment) and explored between-subgroup differences in neonatal brain volumes (voxel-wise Tensor-Based-Morphometry), functional connectivity (voxel-wise degree centrality) and structural connectivity (Tract-Based-Spatial-Statistics). Results showed two- and three-cluster data-driven solutions. The two-cluster solution comprised a 'resilient' subgroup (lower psychopathology and higher IQ, executive function and socio-emotional scores) and an 'at-risk' subgroup (poorer behavioral and cognitive outcomes). No neuroimaging differences between the resilient and at-risk subgroups were found. The three-cluster solution showed an additional third 'intermediate' subgroup, displaying behavioral and cognitive outcomes intermediate between the resilient and at-risk subgroups. The resilient subgroup had the most cognitively stimulating home environment and the at-risk subgroup showed the highest neonatal clinical risk, while the intermediate subgroup showed the lowest clinical, but the highest socio-demographic risk. Compared to the intermediate subgroup, the resilient subgroup displayed larger neonatal insular and orbitofrontal volumes and stronger orbitofrontal functional connectivity, while the at-risk group showed widespread white matter microstructural alterations. These findings suggest that risk stratification following VPT birth is feasible and could be used translationally to guide personalized interventions aimed at promoting children's resilience.
Asunto(s)
Recien Nacido Extremadamente Prematuro , Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Niño , Nacimiento Prematuro/diagnóstico por imagen , Nacimiento Prematuro/patología , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Edad GestacionalRESUMEN
The development of connectivity between the thalamus and maturing cortex is a fundamental process in the second half of human gestation, establishing the neural circuits that are the basis for several important brain functions. In this study, we acquired high-resolution in utero diffusion magnetic resonance imaging (MRI) from 140 fetuses as part of the Developing Human Connectome Project, to examine the emergence of thalamocortical white matter over the second to third trimester. We delineate developing thalamocortical pathways and parcellate the fetal thalamus according to its cortical connectivity using diffusion tractography. We then quantify microstructural tissue components along the tracts in fetal compartments that are critical substrates for white matter maturation, such as the subplate and intermediate zone. We identify patterns of change in the diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester, such as the disassembly of radial glial scaffolding and the lamination of the cortical plate. These maturational trajectories of MR signal in transient fetal compartments provide a normative reference to complement histological knowledge, facilitating future studies to establish how developmental disruptions in these regions contribute to pathophysiology.