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
Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15206, USA.
Division of Cardiology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
J Clin Med. 2024 Sep 27;13(19):5772. 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.
先天性心脏病（CHD）婴儿的脑磁共振成像（MRI）显示，通过基于皮质的半定量评分评估，脑发育不成熟。我们的主要目的是开发一种基于婴儿边缘旁相关皮质下的半定量发育异常评分，称为脑发育异常评分（BDS），以检测CHD婴儿与健康对照相比的异常情况，并其次预测临床结果。我们还在左心发育不全综合征的临床前小鼠模型中验证了我们的BDS。将源自CHD婴儿结构MRI的边缘旁相关皮质下BDS与健康对照进行比较，并与临床风险因素、局部脑容量、喂养和18个月神经发育结果相关联。BDS在一个已知的名为携带两个致病基因和的CHD小鼠模型中得到验证。为了关联临床发现，对动物完成了RNA测序。与健康对照（n = 92）相比，BDS显示CHD婴儿（n = 215）中边缘旁相关皮质下异常（包括嗅觉、小脑和海马异常）的发生率很高。BDS与皮质成熟度降低、发育迟缓、语言和喂养结果差以及住院时间延长相关。动物（n = 63）显示出类似的BDS结果，RNA测序分析显示神经发育和喂养途径改变。突变体与更严重的BDS相关，而与较轻的表型相关。我们的BDS对CHD和健康对照之间的发育异常差异敏感，并可预测不良结果。人类和突变体之间存在类似的边缘旁和皮质下异常谱，提示共同的遗传机制病因。
