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Structural Covariance Analysis of Altered Brain Development in Neonates With Congenital Heart Disease After Surgery
Mirthe E M van der Meijden1, Barat Gal-Er1, Benjamin Clayden1
1Research Department of Early Life Imaging, Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
Insights
Neonates with congenital heart disease (CHD) show altered brain development, with significant postoperative and perioperative morphological changes identified using Structural Covariance Component (SCC) analysis. These changes in brain regions were region-specific and not linked to perioperative risk factors.
Area of Science:
- Neuroimaging
- Pediatric Cardiology
- Developmental Neuroscience
Background:
- Congenital heart disease (CHD) significantly impacts neonatal brain development, leading to reduced brain volumes and enlarged cerebrospinal fluid (CSF) spaces.
- Perioperative morphological brain changes in neonates with CHD are not fully understood.
Purpose of the Study:
- To identify brain regions with differing spatial patterns of expansion and contraction in neonates with CHD post-intervention compared to controls.
- To assess perioperative brain changes and the influence of risk factors using Structural Covariance Component (SCC) analysis.
Main Methods:
- Prospective study involving 41 neonates with CHD and 359 healthy controls, utilizing 3T T2-weighted MRI.
- Structural Covariance Component (SCC) analysis was performed on motion-corrected images to identify patterns of coordinated brain region expansion and contraction.
- Statistical analyses included general linear models, mixed-effects models, and Spearman's rank correlation, with adjustments for covariates and False Discovery Rate correction.
Main Results:
- Sixteen of 40 SCCs revealed significant differences between neonates with CHD post-surgery and controls, affecting white matter, gray matter, brainstem, and CSF.
- Seven of these SCCs also demonstrated significant perioperative changes; an additional nine SCCs showed significant perioperative changes exclusively.
- Perioperative risk factors such as age at surgery, cardiopulmonary bypass duration, and ICU stay were not associated with observed perioperative brain changes.
Conclusions:
- This study highlights region-specific alterations in brain morphology in neonates with CHD following cardiac intervention.
- Significant perioperative changes in brain morphology were observed in neonates with CHD, independent of key perioperative risk factors.
Background:
Brain development is altered in neonates with congenital heart disease (CHD), with well-characterised reductions in regional brain volumes and enlargement of CSF spaces. However, perioperative morphological changes remain incompletely understood.
Purpose:
To identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and controls, assess perioperative changes and effects of perioperative risk factors, using Structural Covariance Component (SCC) analysis.
Study Type:
Prospective.
Population:
Forty-one neonates with CHD (male = 20) who underwent cardiac surgery or catheterization and 359 healthy neonates (male = 185).
Field Strength And Sequence:
3T T2-weighted turbo-spin-echo sequence.
Assessment:
Images were motion-corrected and reconstructed using a neonatal algorithm. Jacobian determinants calculated from non-linear image registration to a template were input into an Independent Component Analysis to identify SCCs (N = 40). SCC weightings were extracted, reflecting the degree to which the covariance pattern is expressed per neonate.
Statistical Tests:
Postoperative SCC weightings were compared to those of controls using a general linear model or robust regression. Perioperative change was assessed using a linear mixed effects model, and associations between perioperative differences and age at surgery, cardiopulmonary bypass duration, and postoperative pediatric intensive care unit stay were assessed using partial Spearman's rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate, significant at p < 0.05.
Results:
Sixteen of the 40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical- and deep gray matter, brainstem, and CSF (f2 partial = 0.02-0.04), with seven also showing significant perioperative change (f2 partial < 0.01-0.27). An additional nine SCCs only showed significant perioperative change (f2 partial < 0.01-0.14). Perioperative risk factors were not associated with perioperative change (p > 0.463).
Data Conclusion:
This work highlights region-specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD.
Evidence Level:
1.
Technical Efficacy:
Stage 3.
