Validation of a Paralimbic-Related Subcortical Brain Dysmaturation MRI Score in Infants with Congenital Heart Disease

Area of Science:

• Neuroscience
• Developmental Biology
• Medical Imaging

Background:

• Infants with congenital heart disease (CHD) exhibit brain immaturity on MRI, previously assessed using cortical scores.
• Paralimbic-related subcortical brain structures are crucial for development and function, yet their assessment in CHD infants is limited.

Purpose of the Study:

• To develop and validate a semi-quantitative brain dysplasia score (BDS) for detecting subcortical abnormalities in infants with CHD.
• To assess the BDS's ability to predict clinical outcomes and neurodevelopmental trajectories in CHD infants.
• To validate the BDS in a preclinical mouse model of hypoplastic left heart syndrome.

Main Methods:

• Structural MRIs from CHD infants (n=215) and healthy controls (n=92) were analyzed to derive the paralimbic-related subcortical BDS.
• BDS was correlated with clinical factors, regional brain volumes, feeding status, and 18-month neurodevelopmental outcomes.
• The BDS was validated in a CHD mouse model (Ohia) with identified genetic mutations (Sap130, Pchda9), using RNA-Seq for pathway analysis.

Main Results:

• The BDS identified a high incidence of subcortical abnormalities (olfactory, cerebellar, hippocampal) in CHD infants compared to controls.
• BDS correlated significantly with reduced cortical maturation, developmental delays, impaired language and feeding, and longer hospital stays.
• The Ohia mouse model showed similar BDS findings, with RNA-Seq revealing altered neurodevelopmental and feeding pathways; Sap130 mutants had a more severe BDS.

Conclusions:

• The developed BDS is a sensitive tool for identifying brain dysmaturation in CHD infants and predicting adverse clinical outcomes.
• The findings in the Ohia mouse model suggest shared genetic mechanisms underlying paralimbic and subcortical abnormalities in human CHD.
• The BDS offers a novel approach to characterizing brain abnormalities in CHD, potentially guiding early interventions and research into genetic etiologies.