Single ventricle (SV) lesions are the leading cause of morbidity and mortality from congenital heart disease (CHD) in the United States. The surgical reconstruction is performed in stages ultimately leading to the final stage - the Fontan operation. These children have greater neurodevelopmental (ND) deficits than the general population and other forms of CHD. One component to ultimate ND outcome is cerebral blood flow (CBF); preliminary data from our lab in SV as well as in the literature suggests that CBF is related to ND and cognitive function. These children are especially at risk for altered CBF because of the altered blood flow caused by the various surgeries and congenital heart lesion. For example, in the first stage of surgery, an aortic to pulmonary shunt is created; this access to the low resistance pulmonary circulation from the systemic circulation allows for a runoff physiology, potentially stealing blood away from the brain. Brain abnormalities, which can be seen in SV patients, have also been linked to ND. There is a pressing need to understand CBF and brain abnormalities as it relates to ND in childhood; this rapid growth stage may be especially important to ultimate cognitive function which not only has a social/humanistic impact but an economic one as well. In addition, it may ultimately lead to modifications in management such as timing of surgery and identifying children at risk for poor ND outcome to implement early interventions. This is a prospective, single center study submitted as a renewal of our nearly completed NIH RO1 CBF study in SV patients and seeks to relate cerebral anatomy, hemodynamics and cerebral oxygen metabolism (CMRO2) to ND outcome, using our original patient cohort as a basis. This study will utilize magnetic resonance imaging (MRI) to measure blood flow and visualize cerebral anatomy by phase contrast MRI, arterial spin labeling, and anatomic imaging such as T1 weighted sequences. MRI utilizing susceptometry, a newly developed technique by one of the co-investigators, will assess CMRO2. This combination of MRI capabilities offers a unique opportunity for a comprehensive cerebral assessment in one study; by combining this with ND testing, this study will determine the relationship of CBF and brain abnormalities to ND outcomes by recalling patients from our original NIH CBF study to undergo an MRI and ND, correlating with data from the original NIH grant and the current proposal. This will also allow for determining how CBF and brain abnormalities evolve in SV patients over time. Additional SV patients and normal controls will be recruited to enrich the population. This study will also determine the relationship between CMRO2 with brain lesions and ND outcome. The impact of this study is important to optimize ND in SV patients. Critical information on the effect of cerebral anatomy, hemodynamics and metabolism on ND must be obtained if it is to improve. The renewal will fill key knowledge gaps by efficiently capitalizing n the expertise of our multidisciplinary team. The findings from this study will provide critical dat that will inform a future interventional trial on improving ND outcomes in SV.

Public Health Relevance

Children with hearts containing only one pumping chamber are not only the leading cause of death and complications from all children born with malformed hearts in the United States but have a much higher rate of social, behavioral and educational problems than the general population which not only has a humanistic impact but an economic one as well. This may be due to altered blood flow to the brain and by understanding how this blood flow affects these children's health, especially important in this rapid growth stage, we may be able to help them grow up to lead better lives by implementing early intervention programs or changing the timing of their surgeries. Using MRI and specialized educational, social and behavioral testing, we may be able to have a positive impact on these children, allowing them to grow up to be more productive members of society.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Evans, Frank
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Children's Hospital of Philadelphia
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