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Magnetic resonance imaging (MRI) is noninvasive and nonionizing and offers excellent soft-tissue contrast and good spatial resolution, providing anatomical detail that cannot be obtained by any other imaging modality. In this review, we discuss the imaging findings in perinatal arterial stroke, hypoxic ischemic encephalopathy, metabolic abnormalities, and infection. Conventional imaging can detect patterns of injury that relate to the etiology and timing of an insult and provide valuable information about prognosis. In many cases, diffusion-weighted imaging provides additional information to conventional MRI, and we recommend its use in all clinical MRI investigations. We also consider the utility of tools such as functional MRI, diffusion tensor imaging, and diffusion tractography in the neonatal population. © Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development and pathology in the preterm brain. This imaging modality is useful for assessing numerous pathologies including periventricular leukomalacia, intraventricular haemorrhage/germinal layer haemorrhage, and periventricular haemorrhagic infarction, and can help to predict outcome in these infants. MRI has also allowed the detection of posterior fossa lesions, which are not easily seen with ultrasound. Additionally, and perhaps most relevant, quantitative MR studies have shown differences between the normal appearing preterm brain at term equivalent age and term born infants, confirming that the brain develops differently in the ex utero environment. Further studies using quantifiable MR techniques will improve our understanding of the effects of the ex utero environment, including aspects of neonatal intensive care on the developing brain. [ABSTRACT FROM AUTHOR]

Background: Very low birth weight (VLBW) infants (weight <1500 g) are increasingly cared for without prolonged periods of positive pressure ventilation (PPV).Aims: To develop a system for 3.0 T magnetic resonance (MR) image acquisition from VLBW infants who are not receiving PPV, and to test the clinical stability of a consecutive cohort of such infants.Design: Seventy VLBW infants whose median weight at image acquisition was 940 g (590-1490) underwent brain MR imaging with the developed care system as participants in research. Twenty infants (29%) received nasal continuous positive airway pressure (nCPAP), 28 (40%) received supplemental oxygen by nasal cannulae, and 22 (31%) breathed spontaneously in air during the MR examination.Results: There were no significant adverse events. Seventy-six percent had none or transient self-correcting oxygen desaturations. Desaturations that required interruption of the scan for assessment were less common among infants receiving nCPAP (2/20) or breathing spontaneously in air (2/22), compared with those receiving nasal cannulae oxygen (13/28), p=0.003. Sixty-four (91%) infants had an axillary temperature > or =36 degrees C at completion of the scan (lowest 35.7 degrees C), There was no relationship between weight (p=0.167) or use of nCPAP (p=0.453) and axillary temperature <36 degrees C. No infant became hyperthermic.Conclusion: VLBW infants who do not require ventilation by endotracheal tube can be imaged successfully and safely at 3.0 T, including those receiving nCPAP from a customised system. [ABSTRACT FROM AUTHOR]

Background: Altered structural brain development has been identified in fetuses with congenital heart disease (CHD), suggesting that the neurodevelopmental impairment observed later in life might originate in utero. There are many interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations, such as altered cerebral substrate delivery and aberrant fetal hemodynamics., Methods and Results: We extracted structural covariance networks from the log Jacobian determinants of 435 in utero T2 weighted image magnetic resonance imaging scans, (n=67 controls, 368 with CHD) acquired during the third trimester. We fit general linear models to test whether age, sex, expected cerebral substrate delivery, and CHD diagnosis were significant predictors of structural covariance. We identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnosis across a variety of structural covariance networks, including primary motor and sensory cortices, cerebellar regions, frontal cortex, extra-axial cerebrospinal fluid, thalamus, brainstem, and insula, consistent with widespread coordinated aberrant maturation of specific brain regions over the third trimester., Conclusions: Structural covariance networks offer a sensitive, data-driven approach to explore whole-brain structural changes without anatomical priors. We used them to stratify a heterogenous patient cohort with CHD, highlighting similarities and differences between diagnoses during fetal neurodevelopment. Although there was a clear effect of abnormal fetal hemodynamics on structural brain maturation, our results suggest that this alone does not explain all the variation in brain development between individuals with CHD.

Congenital heart disease is associated with impaired early brain development and adverse neurodevelopmental outcomes. This study investigated how individualized measures of preoperative cortical gyrification index differ in 142 infants with congenital heart disease, using a normative modelling approach with reference data from 320 typically developing infants. Gyrification index Z -scores for the whole brain and six major cortical areas were generated using two different normative models: one accounting for post-menstrual age at scan, post-natal age at scan and sex, and another additionally accounting for supratentorial brain volume. These Z -scores were compared between congenital heart disease and control groups to test the hypothesis that cortical folding in infants with congenital heart disease deviates from the normal developmental trajectory. The relationships between whole-brain gyrification index Z -scores from the two normative models and both cerebral oxygen delivery and neurodevelopmental outcomes were also investigated. Global and regional brain gyrification was significantly reduced in neonates with congenital heart disease, but not when supratentorial brain volume was accounted for. This finding suggests that whilst cortical folding is reduced in congenital heart disease, it is primarily driven by a reduction in brain size. There was a significant positive correlation between cerebral oxygen delivery and whole-brain gyrification index Z -scores in congenital heart disease, but not when supratentorial brain volume was accounted for. Cerebral oxygen delivery is therefore likely to play a more important role in the biological processes underlying volumetric brain growth than cortical folding. No significant associations between whole-brain gyrification index Z -scores and motor/cognitive outcomes or autism traits were identified in the 70 infants with congenital heart disease who underwent neurodevelopmental assessment at 22-months. Our results suggest that chronic in utero and early post-natal hypoxia in congenital heart disease is associated with reductions in cortical folding that are proportional to reductions in supratentorial brain volume., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

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. P FDR -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 P FDR  > 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., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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* (⍴ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* ⍴ = -0.65; fetal brain T2* ⍴ = -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 (⍴ = 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., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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., (© 2024. The Author(s).)

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., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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 p FDR  < 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, p FDR  = 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., (© 2024. The Author(s).)

Background: Congenital Heart Disease (CHD) is the most common congenital abnormality. Survival rates are over 90%, however infants with CHD remain at high risk of attention and executive function impairments. These abilities are difficult to assess in toddlers because clinical assessments rely on language abilities which are commonly delayed in CHD. Our aim was to characterise visual attention in toddlers with CHD compared to controls and identify associations with parent-rated effortful control., Methods: Thirty toddlers with CHD (19 male, median (IQR) age at assessment 22.2 (22-23.1) months) and 66 controls from the developing human connectome project (36 male, age at assessment 22 (21.5-23.8) months) using eye-tracking tasks designed to assess multiple components of visual attention. Analyses of co-variance and regressions were used to identify differences between groups and relationships between gaze behaviours and parent-rated effortful control., Results: Toddlers with CHD were less accurate when switching behaviours (set-shifting) [median (IQR) 79%, (28-100)] compared to controls [100% (86-100), pFDR = 0.032], with worse accuracy associated with lower parent-rated effortful control in CHD but not controls (interaction pFDR = 0.028). Reaction times were slower during selective [CHD 1243 ms (986-1786), controls 1065 ms (0851-1397), pFDR<0.001] and exogenous attention tasks [CHD 312 ms (279-358), control 289 (249-331), (pFDR = 0.032) and endogenous attention was less mature (prolonged looks at facial stimuli CHD 670 ms (518-885), control 500 ms (250-625), (pFDR = 0.006). These results were unrelated to differences in cognition or socioeconomic status. In contrast, the allocation of attentional resources was preserved in CHD., Conclusions: We identified a profile of altered attention and early executive functioning development in CHD. Eye-tracking may provide clinically feasible, early objective measures of attention and executive function development in CHD., Competing Interests: The authors have declared they have no competing or potential conflicts of interest., (© 2024 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. This work received funding from the Medical Research Council UK (MR/V002465/1; MR/L011530/1), Action Medical Research (GN2630), the British Heart Foundation (FS/15/55/31649), and the European Research Council under the European Union’s Seventh Framework Programme (FP7/20072013/ECR grant agreement no [319456] Developing Human Connectome Project project). This work was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering [WT203148/Z/16/Z]. The study sponsors had no role in study design; collection, analysis and interpretation of data; writing the report; or decision to submit the paper for publication. The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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, β = -0.50). SES was independently associated with cognitive outcome (P < .001, β = 0.26), and LOS with motor outcome (P < .001, β = -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., Competing Interests: Declaration of Competing Interest Financial relationships/disclosures/grants: This research was funded by a Consolidator Grant of the European Society of Paediatric Research (ESPR). WKZ: This research was funded by the Hartekind Foundation and Vrienden van het Wilhelmina Kinderziekenhuis Foundation. CRUCIAL-TRIAL by ZonMw. KCL: This research was funded by the Medical Research Council UK (MR/L011530/1 and MR/V002465/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630) and was supported by the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at Kings College London (WT 203148/Z/16/Z). UCZ: This research was funded by the Mäxi-Foundation Switzerland, the Anna Müller Grocholski Foundation Switzerland and the EMDO Foundation Switzerland. The sponsors were not involved in the study design, the collection, analysis, and interpretation of data, the writing of the report; and the decision to submit the paper for publication., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Introduction: Ultra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system., Methods: Images were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM)., Results: There was no significant difference between temperature before and after scanning ( p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy., Discussion: We demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bridgen, Tomi-Tricot, Uus, Cromb, Quirke, Almalbis, Bonse, De la Fuente Botella, Maggioni, Cio, Cawley, Casella, Dokumaci, Thomson, Willers Moore, Bridglal, Saravia, Finck, Price, Pickles, Cordero-Grande, Egloff, O'Muircheartaigh, Counsell, Giles, Deprez, De Vita, Rutherford, Edwards, Hajnal, Malik and Arichi.)

Very preterm (VPT; < 33 weeks' gestation) toddlers screening positively for autism spectrum conditions (ASC) may display heterogenous neurodevelopmental trajectories. Here we studied neonatal brain volumes and childhood ASC traits evaluated with the Social Responsiveness Scale (SRS-2) in VPT-born toddlers (N = 371; median age 20.17 months) sub-divided into three groups based on their Modified-Checklist for Autism in Toddlers scores. These were: those screening positively failing at least 2 critical items (critical-positive); failing any 3 items, but less than 2 critical items (non-critical-positive); and screening negatively. Critical-positive scorers had smaller neonatal cerebellar volumes compared to non-critical-positive and negative scorers. However, both positive screening groups exhibited higher childhood ASC traits compared to the negative screening group, suggesting distinct aetiological trajectories associated with ASC outcomes., (© 2022. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: PC is supported by the Medical Research Council Centre for Neurodevelopmental Disorders [MR/N026063/1] to undertake this work and received an educational stipend from ISMRM to attend the international ISMRM conference and present this work. FP was employed by the Guy′s & St. Thomas′ NHS Foundation Trust & King’s College London as a senior MR physicist at study outset, during experimental design and initial participant recruitment, he is now a senior clinical scientist employed by Hyperfine Inc., since May 2022–drawing a salary, shares and stock options. RT is an MR sequence developer employed by Hyperfine Inc., and is a holder of shares and stock option of Hyperfine Inc. JOM has institutional funding from the Bill & Melinda Gates Foundation Consortium grant to support research work by his group in neurodevelopment, including data from conventional 3T MRI and Hyperfine scanners–this grant is focused on image analysis and is not commercially sponsored. SW has received funding from the Bill & Melinda Gates Foundation for attendance and travel to sites for training and knowledge exchange during the development and delivery of this project. TA is supported by the UK MRC for a Translational support fellowship [MR/V036874/1] for personal salary, and funding for 3T MRI scans, the MRC Centre for Neurodevelopmental Disorders, King’s College London [MR/N026063/1] for administrative support, funding, and a Clinician Scientist Fellowship [MR/P008712/1]—for personal salary and funding for 3T MRI scans. TA is supported by the EPSRC UK Network grant, co-investigator [EP/W035154/1]. DE and JVH: The Hyperfine machine (Swoop® MR System) was provided by the Bill and Melinda Gates Foundation as part of the Unity Consortium., (© 2023 The Author(s).)

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.

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., (© The Author(s) 2023. Published by Oxford University Press.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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-4 th edition (WISC-IV), autism spectrum condition (ASC) traits with the social responsiveness scale-2 nd 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leoni, Vanes, Hadaya, Kanel, Dazzan, Simonoff, Counsell, Happé, Edwards and Nosarti.)

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., (© 2023. The Author(s).)

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., Competing Interests: SW, MP, LC, DC, AU, VK, VK, KC, AP, JH, MR, EH, SC, JT, JH, AE, JO, TA No competing interests declared, (© 2023, Wilson et al.)

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 (NO 2 ) and particulate matter (PM 2.5 and PM 10 ) 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 PM 10 and lower exposure to NO 2 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 PM 10 and lower exposure to NO 2 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 NO 2 and PM 10 . 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Ultralow-field (ULF) point-of-care MRI systems allow image acquisition without interrupting medical provision, with neonatal clinical care being an important potential application. The ability to measure neonatal brain tissue T 1 is a key enabling technology for subsequent structural image contrast optimization, as well as being a potential biomarker for brain development. Here we describe an optimized strategy for neonatal T 1 mapping at ULF., Methods: Examinations were performed on a 64-mT portable MRI system. A phantom validation experiment was performed, and a total of 33 in vivo exams were acquired from 28 neonates with postmenstrual age ranging from 31 +4 to 49 +0  weeks. Multiple inversion-recovery turbo spin-echo sequences were acquired with differing inversion and repetition times. An analysis pipeline incorporating inter-sequence motion correction generated proton density and T 1 maps. Regions of interest were placed in the cerebral deep gray matter, frontal white matter, and cerebellum. Weighted linear regression was used to predict T 1 as a function of postmenstrual age., Results: Reduction of T 1 with postmenstrual age is observed in all measured brain tissue; the change in T 1 per week and 95% confidence intervals is given by dT 1  = -21 ms/week [-25, -16] (cerebellum), dT 1  = -14 ms/week [-18, -10] (deep gray matter), and dT 1  = -35 ms/week [-45, -25] (white matter)., Conclusion: Neonatal T 1 values at ULF are shorter than those previously described at standard clinical field strengths, but longer than those of adults at ULF. T 1 reduces with postmenstrual age and is therefore a candidate biomarker for perinatal brain development., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease., Methods: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury., Results: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06-4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23-5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20-21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05-1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58-67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20-6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28-95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08-13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07-1.36]) also increased the risk of new cerebral sinus venous thrombosis., Conclusions: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors.