Abstract 13028: Associations Between White Matter Microstructure, Resting and Peak Exercise Oxygen Saturations, and Cognitive Function in Adolescents and Adults With a Fontan Circulation; A Diffusion Brain MRI Study

Introduction: Adolescents and adults with a Fontan circulation demonstrate broad cognitive dysfunction. Neurological alterations and risk factors associated with worse outcomes are poorly characterized. Persisting hypoxemia and reduced exercise tolerance are also common and are associated with long-term morbidity and mortality. This study investigated white matter (WM) microstructure in adolescents and adults with a Fontan circulation and associations with CPET data and cognitive functioning. Methods: Ninety-two participants with a Fontan circulation (aged 13-49 years) underwent diffusion brain MRI. Diffusion tensor imaging MRI metrics were computed for 34 WM tracts of interest; Lower FA and higher MD and RD typically infers WM axonal injury and/or demyelination. Resting SaO 2, peak exercise SaO 2 , and % predicted peak VO 2 (%pred VO 2 ) were measured during CPET. Processing speed and executive function were assessed using Cogstate. Results: Mean resting and peak SaO 2 were 93.1% (± 3.81) and 90.1% (± 4.71) respectively and mean %pred VO 2 was 62.7% (± 18.5); all were significantly lower for participants with a patent fenestration compared to those without (p < 0.05). Mean processing speed and executive function z-scores were -0.72 (± 1.44) and -0.43 (± 1.09), respectively. Significant associations were identified between i) resting SaO 2 and the left corticospinal tract (CST) and bilateral superior longitudinal fasciculus I (SLF-I) ii) peak SaO 2 and bilateral CST, frontopontine tract, and SLF-I and -II, and the right SLF-III, and iii) %pred VO 2 and the right cingulum and left uncinate fasciculus (p < 0.05), whereby lower resting and peak SaO 2 and %pred VO 2 were associated with lower FA and/or higher MD and RD. Paradoxical associations were identified between processing speed and executive function and WM tract metrics (p < 0.05). Conclusion: Persisting hypoxemia and exercise intolerance may have long-term detrimental impact on WM microstructure in people with a Fontan circulation. Paradoxical associations between cognitive functioning and DTI-based metrics could be suggestive of compensatory WM remodeling. Longitudinal investigations are required to investigate the mechanisms and trajectory of altered WM microstructure in this cohort.