Congenital heart disease (CHD) is the most common congenital anomaly, with single ventricle (SV) defects accounting for nearly 10% of all CHD. SV defects tend to be the most severe forms of CHD: all patients born with SV require multiple open heart surgeries, often beginning in the neonatal period, ultimately leading to the Fontan procedure. Due to improvements in surgical procedures and medical care, more patients are surviving into adolescence and adulthood. Brain imaging and pathology studies have shown that patients with SV have differences in brain structure and metabolism even before the first surgery, and as early as in utero. Furthermore, a significant number of patients have new or more severe lesions after the initial surgery, and many still have brain abnormalities into early childhood. However, there are no detailed brain structural data of SV patients in adolescence. Our group recruited a large cohort of post-Fontan SV patients aged 10-19 years. Separate analyses of neuropsychological and behavioral outcomes in these patients show deficits in multiple areas of cognition, increased rates of attention deficit-hyperactivity disorder (ADHD), and increased use of remedial and/or special education services compared to a control group. Post-Fontan adolescents have more gross brain abnormalities, including evidence of chronic ischemic stroke. Furthermore, there are widespread reductions in cortical and subcortical gray matter volume and cortical thickness, some of which are associated with medical and surgical variables. Diffusion tensor imaging (DTI) analyses show widespread areas of altered white matter microstructure in deep subcortical and cerebellar white matter. In this dissertation, I use graph theory methods to characterize structural connectivity based on gray matter (cortical thickness covariance) and white matter (DTI tractography), and examine associations between brain structure and neurodevelopment. I found that brain network connectivity differs in post-Fontan patients compared with controls, both at the global and regional level. Additionally, deficits in overall network structure were associated with impaired neurodevelopment in several domains, including general intelligence, executive function, and visuospatial skills. These data suggest that early neuroprotection should be a major focus in the care of SV patients, with the goal of improving long-term neurodevelopmental outcomes
