PROJECT SUMMARY/ ABSTRACT Adolescents with congenital heart disease (CHD) show brain injury in regions (hippocampus, frontal cortex, temporal, and parietal), which control cognition. Abnormalities in these sites are associated with cognitive deficits. However, the underlying cause of brain injury in these areas in CHD is unclear. Alteration in cerebral artery integrity (measured by arterial transit time [ATT]), which is associated with neural injury in other diseases, is a potential cause of brain injury in CHD. However, there are no published reports of cerebral artery integrity in CHD or regarding any associations between cerebral artery integrity, brain injury, and cognition in this condition. We will use a comparative study design, 80 subjects (40 CHD / 40 Healthy controls), with inclusion criteria for CHD will be subjects between 14-18 years of age, have undergone surgical repair or palliation, and controls will be age- and gender-matched to CHD subjects. Using non-invasive brain magnetic resonance imaging (MRI) procedures, our preliminary study is the first to report abnormalities in ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures) in CHD and that these changes are associated with brain injury (as examined by diffusion tensor imaging based mean diffusivity [MD], an MRI measure of tissue integrity) in the hippocampus, frontal cortex, temporal, and parietal regions in CHD subjects compared to controls. However, while promising, the sample size in this preliminary study was quite small and did not allow us to control for important covariates, such as age and gender. Therefore, the specific aims of this proposal are to: 1) compare ATT values (calculated from diffusion-weighted pCASL) between CHD and age- and gender-matched control subjects; 2) compare regional MD values, derived from diffusion tensor imaging data and cognitive scores (measured by the total Montreal Assessment of Cognition [MoCA] and general memory index (GMI) score from the Wide Range Assessment of Memory and Learning [WRAML2]) between CHD and age- and gender-matched control subjects; 3) examine the relationships between altered ATT (indicating cerebral artery integrity), regional MD values (assessment of injury), and cognitive scores in CHD patients. In summary, CHD patients show significant brain injury in areas that control cognition. These deficits are associated with poor school performance, increased morbidity and mortality, and poorer quality of life. A potential cause of this brain injury may be compromised cerebral artery integrity; however, status of the artery integrity and its association with brain injury and cognition has not been reported in CHD. Information from this study has the potential to disclose a process contributing to brain injury in CHD. Thus, it has important implications on identification of effective treatments for CHD by repairing cerebral artery integrity as used in other conditions (such as stroke and traumatic brain injury), which could dramatically improve cognitive function, reduce mortality and morbidity, and increase quality of life in this high risk patient population.