T2*-Relaxometry MRI to Assess Third Trimester Placental and Fetal Brain Oxygenation and Placental Characteristics in Healthy Fetuses and Fetuses With Congenital Heart Disease.

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.

Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy.

OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative). RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.

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 influence of antenatal imaging on prenatal bonding in uncomplicated pregnancies: a mixed methods analysis.

BACKGROUND: Prenatal bonding describes the emotional connection expectant parents form to their unborn child. Research acknowledges the association between antenatal imaging and enhanced bonding, but the influencing factors are not well understood, particularly for fathers or when using advanced techniques like fetal magnetic resonance imaging (MRI). This study aimed to identify variables which may predict increased bonding after imaging. METHODS: First-time expectant parents (mothers = 58, fathers = 18) completed a two-part questionnaire (QualtricsXM™) about their expectations and experiences of ultrasound (n = 64) or fetal MRI (n = 12) scans in uncomplicated pregnancies. A modified version of the Prenatal Attachment Inventory (PAI) was used to measure bonding. Qualitative data were collected through open-ended questions. Multivariate linear regression models were used to identify significant parent and imaging predictors for bonding. Qualitative content analysis of free-text responses was conducted to further understand the predictors' influences. RESULTS: Bonding scores were significantly increased after imaging for mothers and fathers (p < 0.05). MRI-parents reported significantly higher bonding than ultrasound-parents (p = 0.02). In the first regression model of parent factors (adjusted R2 = 0.17, F = 2.88, p < 0.01), employment status (ß = -0.38, p < 0.05) was a significant predictor for bonding post-imaging. The second model of imaging factors (adjusted R2 = 0.19, F = 3.85, p < 0.01) showed imaging modality (ß = -0.53), imaging experience (ß = 0.42) and parental excitement after the scan (ß = 0.29) were significantly (p < 0.05) associated with increased bonding. Seventeen coded themes were generated from the qualitative content analysis, describing how scans offered reassurance about fetal wellbeing and the opportunity to connect with the baby through quality interactions with imaging professionals. A positive scan experience helped parents to feel excited about parenthood. Fetal MRI was considered a superior modality to ultrasound. CONCLUSIONS: Antenatal imaging provides reassurance of fetal development which affirms parents' emotional investment in the pregnancy and supports the growing connection. Imaging professionals are uniquely positioned to provide parent-centred experiences which may enhance parental excitement and facilitate bonding.

Safeguarding essentials in modern-day paediatrics: inflicted injuries, body maps and section 47 investigations.

The second case in the Safeguarding Essentials in Modern-day Paediatrics series, this article focuses on inflicted injuries, body maps and child protection investigations (CPIs). Using the scenario of a 6-year-old presenting to the emergency department having 'fallen off a swing', this article focuses on key considerations for history taking and examination in cases where you suspect injuries may have been inflicted, and how to discuss raising these suspicions with the family, as well as the importance of accurate body map completion. Also covered are CPIs, giving consideration to the legal framework surrounding these, and relevant useful resources and guidance are provided for dealing with the challenging circumstances that arise when physical abuse is first suspected.

Acute Safeguarding Essentials in Modern-day Paediatrics: Sexual Relationships, Consent and Confidentiality.

As the third case in the acute safeguarding essentials in modern-day paediatrics series, this article focuses on sexual relationships, consent and confidentiality. Using the scenario of a 15-year-old girl presenting to the emergency department with a positive pregnancy test, it begins with a guide to taking a psychosocial history in young people followed by discussion about some of the legality surrounding sexual relationships in adolescents, issues around consent and considerations for confidentiality in this age group.

Assessing within-subject rates of change of placental MRI diffusion metrics in normal pregnancy.

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.

Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease.

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.

Acute safeguarding essentials in modern-day paediatrics: neglect, unsupervised minors and modern slavery.

As part of a case-series exploring acute safeguarding essentials in modern day paediatrics, this article focusses on themes of neglect, unsupervised minors and modern slavery. Considerations around initial management, relevant legislation and useful resources, and available to all professionals involved in safeguarding children.

Acute safeguarding essentials in modern-day paediatrics.

This case series addresses the complexities of child safeguarding in modern-day paediatrics, exploring common themes and key pieces of legislation, while emphasising the centrality of the child's welfare in decision-making at all times. It discusses the evolving nature of child protection, including the importance of a multiagency approach and the rising impact of the internet and social media on child welfare, necessitating awareness of online risks and the development of mitigation strategies. Each article presents a case vignette, prompts for consideration, discussions on specific safeguarding concerns, practical considerations, and relevant legislation. Key learning points are emphasised, with links to additional freely available online resources. Ultimately, the series aims to equip paediatric professionals with the necessary tools and techniques to manage safeguarding cases and prioritise the well-being of children and young people.

The Developing Human Connectome Project: typical and disrupted perinatal functional connectivity.

The Developing Human Connectome Project is an Open Science project that provides the first large sample of neonatal functional MRI data with high temporal and spatial resolution. These data enable mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organization in humans. Here, we characterize in unprecedented detail the maturation and integrity of resting state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder, which occur frequently in preterm children. Overall, we found a robust, modular, symmetrical functional brain organization at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.

Fifteen-minute consultation: Baby with jaundice in the first 2 weeks of life.

There are multiple causes of jaundice in the first 2 weeks of life. The aim of this article is to help explain what these causes are and why they occur. It discusses how to focus on the history, examination and investigations in such cases. Initial management will vary depending on the clinical context; as such, this article also outlines the initial management of the most common scenarios.

Fifteen-minute consultation: Investigation and management of hypoglycaemia in the term-born infant.

Hypoglycaemia in term infants is very common. Deciding on appropriate investigations and management is often challenging. The aims of this article are to help with understanding when, how and why to investigate symptoms of hypoglycaemia in full-term infants (born ≥37 weeks' gestational age).

The team that plays together stays together: the effect of departmental Christmas party attendance on team cohesion within a healthcare setting.

OBJECTIVES: To understand the effect of attendance at departmental Christmas parties on cohesion and teamwork within the healthcare setting. METHOD DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS/OUTCOME MEASURES: We used the 'Team Development Measure' questionnaire to assess team cohesiveness among healthcare professionals before and after departmental Christmas parties took place. A pooled mean score (PMS) of responses was used to compare between groups. RESULTS: There were no significant differences in perceived measures of team cohesion when comparing responses before (PMSbefore=1.86±0.20) and after (PMSafter=1.91±0.22) the departmental Christmas party (p=0.37), nor was there a significant difference when comparing responses from attendees (PMSbefore=1.83±0.23, PMSafter=1.89±0.24, p=0.52) or non-attendees (PMSbefore=1.84±1.47, PMSafter=1.83±0.15, p=0.91). No difference was observed between professional groups (PMSdoctors=1.85±0.23, PMSnurses=1.95±0.18, p=0.064). CONCLUSION: Attendance at departmental Christmas parties does not seem to result in improved team cohesion.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease.

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.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease.

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.

Correlation of fetal lung area with MRI derived pulmonary volume.

BACKGROUND: Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation. METHODS: Fetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area. RESULTS: Datasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort [both lungs = 0.982]. CONCLUSION: MRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period.

Preeclampsia Associated Differences in the Placenta, Fetal Brain, and Maternal Heart Can Be Demonstrated Antenatally: An Observational Cohort Study Using MRI.

BACKGROUND: Preeclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multiorgan approach to magnetic resonance imaging (MRI) investigation of preeclampsia, with the acquisition of maternal cardiac, placental, and fetal brain anatomic and functional imaging. METHODS: An observational study was performed recruiting 3 groups of pregnant women: those with preeclampsia, chronic hypertension, or no medical complications. All women underwent a cardiac MRI, and pregnant women underwent a placental-fetal MRI. Cardiac analysis for structural, morphological, and flow data were undertaken; placenta and fetal brain volumetric and T2* (which describes relative tissue oxygenation) data were obtained. All results were corrected for gestational age. A nonpregnant cohort was identified for inclusion in the statistical shape analysis. RESULTS: Seventy-eight MRIs were obtained during pregnancy. Cardiac MRI analysis demonstrated higher left ventricular mass in preeclampsia with 3-dimensional modeling revealing additional specific characteristics of eccentricity and outflow track remodeling. Pregnancies affected by preeclampsia demonstrated lower placental and fetal brain T2*. Within the preeclampsia group, 23% placental T2* results were consistent with controls, these were the only cases with normal placental histopathology. Fetal brain T2* results were consistent with normal controls in 31% of cases. CONCLUSIONS: We present the first holistic assessment of the immediate implications of preeclampsia on maternal heart, placenta, and fetal brain. As well as having potential clinical implications for the risk stratification and management of women with preeclampsia, this gives an insight into the disease mechanism.