Relationships Between Regional Cerebral Blood Flow and Neurocognitive Outcomes in Children and Adolescents With Congenital Heart Disease

Published:November 09, 2021DOI:
      To identify regional cerebral blood flow (rCBF) alterations in children and adolescents with congenital heart disease (CHD) in relation to neurocognitive outcomes using a nonbiased data-driven approach. This is a prospective, observational study of children and adolescents with CHD without brain injury and healthy controls using pseudo-continuous arterial spin labeling (pCASL) MRI. Quantitative rCBF was compared between participants with CHD and healthy controls using a voxelwise data-driven method. Mediation analysis was then performed on a voxelwise basis, with the grouping variable as the independent variable, neurocognitive outcomes (from the NIH Toolbox Cognitive Battery) as the dependent variables, and rCBF as the mediator. After motion correction, a total of 80 studies were analyzable (27 for patients with CHD, 53 for controls). We found steeper age-related decline in rCBF among those with CHD compared to normal controls in the insula/ventromedial prefrontal regions (salience network) and the dorsal anterior cingulate and precuneus/posterior cingulate (default mode network), and posterior parietal/dorsolateral prefrontal (central executive network) (FWE-corrected P< 0.05). The reduced rCBF in the default mode/salience network was found to mediate poorer performance on an index of crystallized cognition from the NIH Toolbox Cognitive Battery in those with CHD compared to controls. In contrast, reduced rCBF in the central executive network/salience network mediated reduced deficits in fluid cognition among patients with CHD compared to controls. Regional cerebral blood flow alterations mediate domain-specific differences in cognitive performance in children and adolescents with CHD compared to healthy controls, independent of injury, and are likely related to brain and cognitive reserve mechanisms. Further research is needed to evaluate the potential of interventions in CHD targeting regional cerebral blood flow across lifespan.

      Graphical Abstract



      ASL (arterial spin labeling), CBF (cerebral blood flow), CHD (congenital heart disease), CSF (cerebral spinal fluid), DACC (Dorsal Anterior Cingulate Cortex), DLPC (Dorsolateral prefrontal cortex), DTI (diffusion tensor imaging), FSL (FMRIB Software Library), FWE (Family Wise Error), GLM (general linear model), GM (grey matter), IDL (Interactive Data Language), INS (Insula), MNI (Montreal Neurological Institute), PID (postinversion delay), pCASL (pseudo-continuous arterial spin labeling), PCING (Posterior Cingulate (PCING)), PCU (Precuneus), PP (Posterior Parietal), rCBF (regional cerebral blood flow), SPM8 (statistical parametric mapping maximum 8 regions), WM (white matter), VMPC (Ventrolateral medial prefrontal cortex)
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      Linked Article

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        Seminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 4
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          The paper by Schmithorst et al.1 from Children's Hospital of Pittsburgh describes a study in which children and adolescents with a wide variety of different congenital heart anomalies underwent assessment of regional cerebral blood flow by the relatively new technique of arterial spin labelling using magnetic resonance imaging (MRI). The study confirms many of the findings noted in neonates and young infants previously reported by Nagaraj et al.2 Twenty-seven patients with congenital heart disease with a mean age of 13 years were compared with 53 controls.
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      • Commentary: Explaining Intervention and Exposure Effects: An Introduction to Mediation Analysis
        Seminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 4
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          Medical research is often focused on determining the impact of interventions or exposures on specific health outcomes, but what often remains unknown is how interventions and exposures transmit their effects on health outcomes. These “how” questions refer to the causal mechanisms that explain intervention and exposure effects.1-3 Insight into causal mechanisms underlying intervention and exposure effects is important, as these insights help refine research theories and provide input for the development of effective interventions.
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