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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
1P01NS082330-01A1
Application #
8617423
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Koenig, James I
Project Start
2014-01-01
Project End
2018-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$1,206,092
Indirect Cost
$381,806
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Peyvandi, Shabnam; De Santiago, Veronica; Chakkarapani, Elavazhagan et al. (2016) Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury. JAMA Pediatr 170:e154450
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
Gano, Dawn; Ho, Mai-Lan; Partridge, John Colin et al. (2016) Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns. J Pediatr 178:68-74
Kim, Hosung; Gano, Dawn; Ho, Mai-Lan et al. (2016) Hindbrain regional growth in preterm newborns and its impairment in relation to brain injury. Hum Brain Mapp 37:678-88
Kim, Hosung; Joo, EunYeon; Suh, Sooyeon et al. (2016) Effects of long-term treatment on brain volume in patients with obstructive sleep apnea syndrome. Hum Brain Mapp 37:395-409
Tam, Emily W Y; Chau, Vann; Barkovich, A James et al. (2016) Early postnatal docosahexaenoic acid levels and improved preterm brain development. Pediatr Res 79:723-30
Kansagra, Akash P; Mabray, Marc C; Ferriero, Donna M et al. (2016) Microstructural maturation of white matter tracts in encephalopathic neonates. Clin Imaging 40:1009-13
Gano, Dawn; Andersen, Sarah K; Partridge, J Colin et al. (2015) Diminished white matter injury over time in a cohort of premature newborns. J Pediatr 166:39-43
Peyvandi, S; Feldstein, V A; Hirose, S et al. (2015) Twin-reversed arterial perfusion sequence associated with decreased fetal cerebral vascular impedance. Ultrasound Obstet Gynecol 45:447-51
Chen, Yiran; Tymofiyeva, Olga; Hess, Christopher P et al. (2015) Effects of rejecting diffusion directions on tensor-derived parameters. Neuroimage 109:160-70

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