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

• Published in: Journal of clinical medicine 2024-09, Vol.13 (19), p.5772
• Main Authors: Reynolds, William T, Votava-Smith, Jodie K, Gabriel, George, Lee, Vincent K, Rajagopalan, Vidya, Wu, Yijen, Liu, Xiaoqin, Yagi, Hisato, Slabicki, Ruby, Gibbs, Brian, Tran, Nhu N, Weisert, Molly, Cabral, Laura, Subramanian, Subramanian, Wallace, Julia, Del Castillo, Sylvia, Baust, Tracy, Weinberg, Jacqueline G, Lorenzi Quigley, Lauren, Gaesser, Jenna, O'Neil, Sharon H, Schmithorst, Vanessa, Panigrahy, Ashok, Ceschin, Rafael, Lo, Cecilia W
• Format: Article
• Language: English
• Subjects: Babies; Brain research; Cardiovascular disease; Congenital diseases; Congenital heart disease; Datasets; Development and progression; Genetic disorders; Gestational age; Heart surgery; Hypotheses; Hypoxia; Infants; Magnetic resonance imaging; Medical imaging; Medical imaging equipment; Medical research; Morphology; Mutation; Neurogenesis; Neuroimaging; Pediatric cardiology; Proteins; Traumatic brain injury
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13195772

Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, termed brain dysplasia score (BDS), to detect abnormalities in CHD infants compared to healthy controls and secondarily to predict clinical outcomes. We also validated our BDS in a preclinical mouse model of hypoplastic left heart syndrome. A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was compared to healthy controls and correlated with clinical risk factors, regional cerebral volumes, feeding, and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named with two disease-causing genes, and . To relate clinical findings, RNA-Seq was completed on animals. BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants ( = 215) compared to healthy controls ( = 92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. animals ( = 63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. mutants correlated with a more severe BDS, whereas correlated with a milder phenotype. Our BDS is sensitive to dysmaturational differences between CHD and healthy controls and predictive of poor outcomes. A similar spectrum of paralimbic and subcortical abnormalities exists between human and mutants, suggesting a common genetic mechanistic etiology.