This grant proposes to study both structural and functional correlates of brain developmental maturation and network organization using advanced imaging techniques in our human populations and similar correlates in newborn rodents with a focus on defining basic mechanisms of repair. The grant will encompass three projects and two cores: Project I) repair after ischemic injury in the term newborn - using both structural and metabolic serial imaging to evaluate how the injuries have altered the brain, its response to injury in the perinatal period, and how structural connectivity relates to neurodevelopmental outcome. This cohort will include babies treated with hypothermia. Project II) repair in high risk newborns with congenital heart disease- there is delayed brain development in this high risk population. Using structural and metabolic imaging, we will determine whether this disorder of development is associated with abnormalities in brain connectivity and functional outcome. Project III) repair after early preterm birth - our data show many preterm infants to have abnormalities of cerebellar maturation, abnormalities of white matter development or progressive white matter disease with infection. Using structural and metabolic imaging, we will determine whether altered patterns of connectivity are consistent or variable, whether recovery from these insults is possible and whether connectivity is permanently or transiently disrupted by these early ex-utero life events. There is an administrative Core for data management including biostatistical support, budgetary oversight, training and seminars. The Imaging and Neurobehavior Core (Services Core) will support the three human imaging projects by ensuring standardization of methods and tracking of imaging acquisition at the various testing time points. In addition, this Core will provide Neurobehavioral testing at all of the follow-up visits, and will be responsible for tracking patients for all projets.
Our program project will enable us to determine how the newborn brain repairs itself after perturbations in development as well as after injury and early birth. Th focus on repair will enable us to harness our understandings learned through these investigations to bring novel therapies to newborns with brain injury.
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