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
Graphical Abstract
Keywords
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 09, 2021
Footnotes
Funding: This work was supported by the Department of Defense (W81XWH-16-1-0613), the National Heart, Lung and Blood Institute (R01 HL152740-1, R01 HL128818-05), and the National Heart, Lung and Blood Institute with National Institute on Aging (R01HL128818-05 S1). IRB STUDY19040003 (previously PRO16040368) originally approved 08/09/2016, current approval 03/27/2020-03/23/2021.
Conflicts of Interest: No conflict of interest to declare.
Our study was approved by the institutional IRB and parental/patient consent was obtained.
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- Commentary: Measurement of Regional Blood Flow in the Brain by Magnetic Resonance Imaging Raises New Questions for Adolescents With Congenital Heart DiseaseSeminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 4
- PreviewThe 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.
- Full-Text
- Preview
- Commentary: Explaining Intervention and Exposure Effects: An Introduction to Mediation AnalysisSeminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 4
- PreviewMedical 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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