Magnetic resonance (MR) imaging studies have demonstrated reduced global and regional brain volumes in infants with congenital heart disease (CHD). This study aimed to provide a more detailed evaluation of altered structural brain development in newborn infants with CHD compared to healthy controls using tensor-based morphometry (TBM). We compared brain development in 64 infants with CHD to 192 age- and sex-matched healthy controls. T2-weighted MR images obtained prior to surgery were analysed to compare voxel-wise differences in structure across the whole brain between groups. Cerebral oxygen delivery (CDO2) was measured in infants with CHD (n = 49) using phase contrast MR imaging and the relationship between CDO2 and voxel-wise brain structure was assessed using TBM. After correcting for global scaling differences, clusters of significant volume reduction in infants with CHD were demonstrated bilaterally within the basal ganglia, thalami, corpus callosum, occipital, temporal, parietal and frontal lobes, and right hippocampus (p < 0.025 after family-wise error correction). Clusters of significant volume expansion in infants with CHD were identified in cerebrospinal fluid spaces (p < 0.025). After correcting for global brain size, there was no significant association between voxel-wise brain structure and CDO2. This study localizes abnormal brain development in infants with CHD, identifying areas of particular vulnerability.
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We are indebted to the families who supported this study. We thank the staff from the St Thomas’ Neonatal Intensive Care Unit; the Evelina London Children’s Hospital Foetal and Paediatric Cardiology Departments; the Evelina London Paediatric Intensive Care Unit; the Centre for the Developing Brain at King’s College London; our research radiologists, including Sophie Arulkumaran, Kelly Pegoretti, and Olivia Carney; our research radiographers, including Joanna Allsop, Ana Dos Santos Gomes, and Elaine Green; and our neonatal scanning team including Katy Vecchiato, Claire Caldwell, Julia Wurie, José Bueno Conde, Maryann Sharma, Beatriz San-tamaria, Camilla O’Keeffe, and Jacqueline Brandon. This research was funded by the Medical Research Council UK (MR/L011530/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630). This work received funding from the European Research Council under the European Union’s Seventh Frame-work Program (FP7/20072013)/ERC grant agreement no. 319456 (dHCP project), and was supported by the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at Kings College London (WT 203148/Z/16/Z), MRC strategic grant (MR/K006355/1), Medical Research Council Centre grant (MR/N026063/1), and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and Kings College London. I.H.X.N. is supported by the NIHR Academic Clinical Fellowship. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
© 2020, The Author(s).