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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Koenig, James I
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Peyvandi, Shabnam; Kim, Hosung; Lau, Joanne et al. (2018) The association between cardiac physiology, acquired brain injury, and postnatal brain growth in critical congenital heart disease. J Thorac Cardiovasc Surg 155:291-300.e3
Kamino, Daphne; Studholme, Colin; Liu, Mengyuan et al. (2018) Postnatal polyunsaturated fatty acids associated with larger preterm brain tissue volumes and better outcomes. Pediatr Res 83:93-101
Tymofiyeva, O; Gano, D; Trevino Jr, R J et al. (2018) Aberrant Structural Brain Connectivity in Adolescents with Attentional Problems Who Were Born Prematurely. AJNR Am J Neuroradiol 39:2140-2147
Barkovich, Matthew J; Xu, Duan; Desikan, Rahul S et al. (2018) Pediatric neuro MRI: tricks to minimize sedation. Pediatr Radiol 48:50-55
Peyvandi, Shabnam; Chau, Vann; Guo, Ting et al. (2018) Neonatal Brain Injury and Timing of Neurodevelopmental Assessment in Patients With Congenital Heart Disease. J Am Coll Cardiol 71:1986-1996
Glass, Hannah C (2018) Hypoxic-Ischemic Encephalopathy and Other Neonatal Encephalopathies. Continuum (Minneap Minn) 24:57-71
Barkovich, Matthew J; Tan, Chin Hong; Nillo, Ryan M et al. (2018) Abnormal Morphology of Select Cortical and Subcortical Regions in Neurofibromatosis Type 1. Radiology 289:499-508
Cui, J; Tymofiyeva, O; Desikan, R et al. (2017) Microstructure of the Default Mode Network in Preterm Infants. AJNR Am J Neuroradiol 38:343-348
Shapiro, Kevin A; Kim, Hosung; Mandelli, Maria Luisa et al. (2017) Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy. Neuroimage Clin 15:572-580
Kim, Hosung; Lepage, Claude; Maheshwary, Romir et al. (2016) NEOCIVET: Towards accurate morphometry of neonatal gyrification and clinical applications in preterm newborns. Neuroimage 138:28-42

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