Dataset Information

Factors associated with MRI success in children cooled for neonatal encephalopathy and controls.

ABSTRACT:

Objective

To investigate if an association exists between motion artefacts on brain MRI and comprehension, co-ordination, or hyperactivity scores in children aged 6-8 years, cooled for neonatal encephalopathy (cases) and controls.

Methods

Case children (n = 50) without cerebral palsy were matched with 43 controls for age, sex, and socioeconomic status. Children underwent T1-weighted (T1w), diffusion-weighted image (DWI) brain MRI and cognitive, behavioural, and motor skills assessment. Stepwise multivariable logistic regression assessed associations between unsuccessful MRI and comprehension (including Weschler Intelligence Scale for Children (WISC-IV) verbal comprehension, working memory, processing speed and full-scale IQ), co-ordination (including Movement Assessment Battery for Children (MABC-2) balance, manual dexterity, aiming and catching, and total scores) and hyperactivity (including Strengths and Difficulties Questionnaire (SDQ) hyperactivity and total difficulties scores).

Results

Cases had lower odds of completing both T1w and DWIs (OR: 0.31, 95% CI 0.11-0.89). After adjusting for case-status and sex, lower MABC-2 balance score predicted unsuccessful T1w MRI (OR: 0.81, 95% CI 0.67-0.97, p = 0.022). Processing speed was negatively correlated with relative motion on DWI (r = -0.25, p = 0.026) and SDQ total difficulties score was lower for children with successful MRIs (p = 0.049).

Conclusions

Motion artefacts on brain MRI in early school-age children are related to the developmental profile.

Impact

Children who had moderate/severe neonatal encephalopathy are less likely to have successful MRI scans than matched controls. Motion artefact on MRI is associated with lower MABC-2 balance scores in both children who received therapeutic hypothermia for neonatal encephalopathy and matched controls, after controlling for case-status and sex. Exclusion of children with motion artefacts on brain MRI can introduce sampling bias, which impacts the utility of neuroimaging to understand the brain-behaviour relationship in children with functional impairments.

SUBMITTER: Woodward K

PROVIDER: S-EPMC10033414 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Factors associated with MRI success in children cooled for neonatal encephalopathy and controls.

Woodward Kathryn K Spencer Arthur P C APC Jary Sally S Chakkarapani Ela E

Pediatric research 20220729 4

<h4>Objective</h4>To investigate if an association exists between motion artefacts on brain MRI and comprehension, co-ordination, or hyperactivity scores in children aged 6-8 years, cooled for neonatal encephalopathy (cases) and controls.<h4>Methods</h4>Case children (n = 50) without cerebral palsy were matched with 43 controls for age, sex, and socioeconomic status. Children underwent T1-weighted (T1w), diffusion-weighted image (DWI) brain MRI and cognitive, behavioural, and motor skills assess ...[more]

PMID: 35906304

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Project description:Therapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischaemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in children aged 6-8 years treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched typically developing controls. Correlations between total motor scores and diffusion properties in major white matter tracts were assessed in 33 cases and 36 controls. In cases, significant correlations (FDR-corrected P < 0.05) were found in the anterior thalamic radiation bilaterally (left: r = 0.513; right: r = 0.488), the cingulate gyrus part of the left cingulum (r = 0.588), the hippocampal part of the left cingulum (r = 0.541), and the inferior fronto-occipital fasciculus bilaterally (left: r = 0.445; right: r = 0.494). No significant correlations were found in controls. We then constructed structural connectivity networks, for 22 cases and 32 controls, in which nodes represent brain regions and edges were determined by probabilistic tractography and weighted by fractional anisotropy. Analysis of whole-brain network metrics revealed correlations (FDR-corrected P < 0.05), in cases, between total motor scores and average node strength (r = 0.571), local efficiency (r = 0.664), global efficiency (r = 0.677), clustering coefficient (r = 0.608), and characteristic path length (r = -0.652). No significant correlations were found in controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores (P = 0.0109) as well as for balance (P = 0.0245) and manual dexterity (P = 0.0233) domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. The subnetwork associated with total motor scores was highly left-lateralised. These findings demonstrate an association between impaired motor function and brain organisation in school-age children treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

Project description:AimTo evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix.MethodMammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography.ResultsMore cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities.InterpretationCooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls.What this paper addsCooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.

Project description:Background: Neonatal encephalopathy (NE) is associated with adverse neurodevelopmental outcome and is linked with systemic inflammation. Pro-inflammatory and anti-inflammatory cytokines are known to play a role in the pathology of NE by activating innate immune cells. Methods: Eighty-seven infants were enrolled including 53 infants with NE of whom 52 received therapeutic hypothermia (TH) and 34 term infant healthy controls (TC). Whole blood sampling was performed in the first 4 days of life, and a 14-spot ELISA Multiplex Cytokine Array was carried out on baseline samples or after stimulation with lipopolysaccharide (LPS) as an additional inflammatory stimulus. The cytokine medians were examined for differences between infants with NE and healthy TC; and then short-term outcomes of Sarnat stage, seizures, and MRI brain were examined within the NE group. The potential of LPS stimulation to predict abnormal MRI was explored using receiver operating characteristic (ROC) curves. Results: At baseline, infants with NE had significantly higher levels of erythropoietin (Epo), interleukin (IL)-6, and IL-1ra and significantly lower vascular endothelial growth factor (VEGF) than had controls. All cytokines were increased after LPS stimulation in infants with NE with an excessive Epo and IL-1ra response than in controls. Infants with NE had lower IL-8, IL-2, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), VEGF, and interferon (IFN)-γ than controls had following LPS. GM-CSF and IFN-γ, IL-1β, IL-1ra, and VEGF were higher on days 1-2 in NE infants with abnormal neuroimaging. GM-CSF, IFN-γ, and TNF-α levels with LPS stimulation were different upon stimulation between normal and abnormal neuroimaging. TNF-α is the only strong cytokine predictor both pre- and post-LPS stimulation of abnormal brain imaging. Conclusions: Altered cytokine responses are found in infants with NE vs. controls, and more significant differences are unmasked by the additional stimulus of LPS, which potentially improves the predictive power of these cytokines for the detection of abnormal MRIs. Infants with NE undergoing TH demonstrate both trained immunity and tolerance, and understanding these responses will facilitate adjunctive immunomodulatory treatments.

Dataset Information

Factors associated with MRI success in children cooled for neonatal encephalopathy and controls.

Objective

Methods

Results

Conclusions

Impact

Publications

Factors associated with MRI success in children cooled for neonatal encephalopathy and controls.

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