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Published on: June 26, 2013
Structural Covariance Networks in the Fetal Brain Reveal Altered Neurodevelopment for Specific Subtypes of Congenital
Siân Wilson1,2,3,4, Daniel Cromb1, Alexandra F Bonthrone1
1Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences King's College London London United Kingdom.
Insights
Fetal brain development is altered in congenital heart disease (CHD), with abnormal hemodynamics impacting neurodevelopment. Structural covariance networks reveal widespread brain region maturation differences in fetuses with CHD.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Cardiology
Background:
- Congenital heart disease (CHD) is linked to altered fetal brain development, suggesting in-utero origins of neurodevelopmental impairments.
- Factors like altered cerebral substrate delivery and fetal hemodynamics may perturb fetal neurodevelopment, leading to structural brain alterations.
Purpose of the Study:
- To investigate whole-brain structural changes in fetuses with CHD using a data-driven approach.
- To identify predictors of structural brain alterations in the third trimester of pregnancy for fetuses with CHD.
Main Methods:
- Extracted structural covariance networks from 435 in utero T2-weighted MRI scans (67 controls, 368 with CHD).
- Utilized log Jacobian determinants from third-trimester scans.
- Applied general linear models to assess predictors like age, sex, cerebral substrate delivery, and CHD diagnosis.
Main Results:
- Identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnoses on structural covariance networks.
- Observed widespread, coordinated aberrant maturation in motor/sensory cortices, cerebellum, frontal cortex, thalamus, brainstem, and insula.
- Demonstrated significant impacts across various brain regions, indicating coordinated developmental changes.
Conclusions:
- Structural covariance networks provide a sensitive, data-driven method for whole-brain analysis without anatomical priors.
- This approach successfully stratified a heterogeneous CHD cohort, revealing diagnostic similarities and differences in fetal neurodevelopment.
- While abnormal fetal hemodynamics significantly affect brain maturation, they do not solely account for all developmental variations in individuals with CHD.
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.
