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

Brain development is closely tied to cardiovascular function, making it crucial to study their interconnectivity, particularly in congenital heart disease (CHD). As the most common birth defect, CHD places children at a higher risk for neurodevelopmental deficits, particularly impairments in executive function (EF), which is critical for decision-making and goal-directed behavior, potentially leading to a diminished quality of life. 

Altered cerebrospinal fluid (CSF) volumes and disrupted CSF circulation may contribute to poor EF. CSF circulation is vital for neurogenesis and brain homeostasis, with abnormalities linked to neurodevelopmental deficits. Since CSF flow is driven by cardiac pulsation, disrupted cardiovascular function common in CHD may impair this mechanism, leading to abnormal CSF dynamics, though this potential link remains unexplored. This study aims to examine the relationship between abnormal CSF flow and EF outcomes in children and adolescents with CHD compared to controls, addressing a critical gap in understanding how CSF disruptions may affect brain development.

We first used Random Forest regression to examine the relationship between CSF volumes, brain macro- and microstructure, and sociodemographic and medical risk factors, showing that CSF volumes predict cognitive flexibility and inhibition subdomains of EF. Next, we employed phase-contrast MRI at the Aqueduct of Sylvius to quantify CSF flow, including a novel assessment of CSF flow deviation across the entire cardiac cycle. We identified CSF flow differences in CHD compared to controls and demonstrated altered CSF flow predicted the inhibition subdomain of EF. We then correlated CSF features with brain dysmaturation, a common sequela of CHD-related structural abnormalities, revealing that CSF characteristics independently predict EF outcomes. Lastly, we examined ciliary motion (CM) of motile cilia for potential links to CSF flow. CM function drives CSF flow at the microscopic level, and CM dysfunction is linked to CHD pathogenesis. We found increased CSF volume and elevated flow in CHD participants with abnormal CM function.

This study highlights the interrelationship between CSF and cardiac, structural, and genetic factors in CHD, and the role of abnormal CSF dynamics in contributing to impaired EF outcomes, underscoring the need for further exploration of these mechanisms.