Quantitative Magnetic Resonance Properties of Cerebrospinal Fluid and Brain Health Outcomes in Pediatric Congenital Heart Disease

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Project Summary/Abstract Children with congenital heart disease (CHD) are more likely to develop neurodevelopmental deficits than the general population. Due to advances in interventional surgical techniques, survival rates for patients with CHD are high, but they face adverse neurodevelopmental challenges – such as cognitive deficits – and attain lower education and social interaction, leading to reduced quality of life. Despite a multitude of studies examining risk factors for adverse neurodevelopment outcomes in children with CHD, only a small proportion of observed variations in cognitive tests can be attributed to these tested exposures. A larger portion of risk factors that may play critical roles in adverse neurodevelopmental outcomes in children with CHD remains to be discovered. One such risk factor is likely to be alterations in cerebrospinal fluid (CSF) characteristics manifested as alterations in volume and flow dynamics. Recent studies show that normal CSF circulation is necessary for healthy neuronal growth and maintenance of a homeostatic environment for normal neuronal function. Abnormalities in the CSF have been linked to neurological diseases such as autism spectrum disorder in children and dementia in adults. In CHD, abnormal CSF findings, especially increased CSF volume, are frequently observed. Increased CSF volume has been shown to be correlated with brain dysmaturation and poor neurodevelopmental outcomes in young children with CHD. Although in the elderly, there are studies that link decreased CSF flow velocities with cognitive impairment. Currently, CSF flow alterations in children with CHD have yet to be examined in vivo, and the possible link between CSF flow and increased volume to cognitive outcomes remains to be explored. This project aims to examine the relationship between disruption in CSF characteristics and neurodevelopmental deficits in children with CHD. We hypothesize that aberrant CSF characteristics (increased volumes and decreased flow velocity) measured using MRI will be powerful multi-modal imaging predictors for neurodevelopmental outcomes in children with CHD. This project leverages a Department of Defense-funded ongoing study at UPMC Children’s Hospital of Pittsburgh involving children with CHD and age-matched healthy controls who receive MRI imaging as well as neuropsychologic testing – including executive function. In this project, we propose measuring intracranial CSF volume (extra-axial and intra-ventricular volume) using structural MRI (T1 and T2 images) and measuring CSF flow velocity through the Aqueduct Silvius using phase-contrast MRI. These CSF measurements will then be correlated with neuropsychological tests assessing executive function. The results from this proposed project will help determine (1) differences in CSF characteristics between children with CHD and healthy controls and (2) any correlation between CSF characteristics and neurodevelopmental outcomes in CHD. Taken together, we hope to develop useful CSF-based imaging biomarkers to prognosticate poor neurodevelopmental outcomes in pediatric patients with CHD.