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Journal Article Epublish 8 citations

PubMed: 36144286 DOI: 10.3390/metabo12090882

Impaired Neurovascular Function Underlies Poor Neurocognitive Outcomes and Is Associated with Nitric Oxide Bioavailability in Congenital Heart Disease.

Metabolites 12(9)

Authors: Vanessa J Schmithorst, Phillip S Adams, Daryaneh Badaly, Vincent K Lee, Julia Wallace, Nancy Beluk, Jodie K Votava-Smith, Jacqueline G Weinberg, Sue R Beers, Jon Detterich, John C Wood, Cecilia W Lo, Ashok Panigrahy

Affiliations

  • Department of Pediatric Radiology, UPMC Children's Hospital, Pittsburgh, PA 15224, USA.
  • Department of Pediatric Anesthesiology, UPMC Children's Hospital, Pittsburgh, PA 15224, USA.
  • Learning and Development Center, Child Mind Institute, New York, NY 10022, USA.
  • Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Heart Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
  • Department of Pediatric Cardiology, UPMC Children's Hospital, Pittsburgh, PA 15224, USA.
  • Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Abstract

We use a non-invasive MRI proxy of neurovascular function (pnvf) to assess the ability of the vasculature to supply baseline metabolic demand, to compare pediatric and young adult congenital heart disease (CHD) patients to normal referents and relate the proxy to neurocognitive outcomes and nitric oxide bioavailability. In a prospective single-center study, resting-state blood-oxygen-level-dependent (BOLD) and arterial spin labeling (ASL) MRI scans were successfully obtained from 24 CHD patients (age = 15.4 ± 4.06 years) and 63 normal referents (age = 14.1 ± 3.49) years. Pnvf was computed on a voxelwise basis as the negative of the ratio of functional connectivity strength (FCS) estimated from the resting-state BOLD acquisition to regional cerebral blood flow (rCBF) as estimated from the ASL acquisition. Pnvf was used to predict end-tidal CO2 (PCO2) levels and compared to those estimated from the BOLD data. Nitric oxide availability was obtained via nasal measurements (nNO). Pnvf was compared on a voxelwise basis between CHD patients and normal referents and correlated with nitric oxide availability and neurocognitive outcomes as assessed via the NIH Toolbox. Pnvf was shown as highly predictive of PCO2 using theoretical modeling. Pnvf was found to be significantly reduced in CHD patients in default mode network (DMN, comprising the ventromedial prefrontal cortex and posterior cingulate/precuneus), salience network (SN, comprising the insula and dorsal anterior cingulate), and central executive network (CEN, comprising posterior parietal and dorsolateral prefrontal cortex) regions with similar findings noted in single cardiac ventricle patients. Positive correlations of Pnvf in these brain regions, as well as the hippocampus, were found with neurocognitive outcomes. Similarly, positive correlations between Pnvf and nitric oxide availability were found in frontal DMN and CEN regions, with particularly strong correlations in subcortical regions (putamen). Reduced Pnvf in CHD patients was found to be mediated by nNO. Mediation analyses further supported that reduced Pnvf in these regions underlies worse neurocognitive outcome in CHD patients and is associated with nitric oxide bioavailability. Impaired neuro-vascular function, which may be non-invasively estimated via combined arterial-spin label and BOLD MR imaging, is a nitric oxide bioavailability dependent factor implicated in adverse neurocognitive outcomes in pediatric and young adult CHD.

MeSH

Heart Diseases, Heart Defects, Congenital, Biological Availability, Blood, Prefrontal Cortex, Default Mode Network

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