Between 13 and 16% of children born in the united States are born prematurely, with nearly 2% of these weighing less than 1500 g (less than three-quarters of a pound). In this latter group, neurological deficits are observed in nearly 90% of those who survive: cerebral palsy is found in 5-10% and deficits in cognition, behavior, or attention is found in about 50%. In 2005, medical costs during the first year of life averaged $41,610, compared to $2830 for a full term baby, for total annual hospital charges of $7.4 billion. Magnetic resonance imaging is being used increasingly to look at the brains of these babies in order to understand why so many have these developmental abnormalities. Most studies have focused upon injury to the white matter of the cerebral hemispheres, but recent studies have discovered frequent abnormalities of development of the cerebellum, a more posterior part of the brain. The cerebellum has traditionally been associated with motor tone and coordination, and more recently has been implicated in cognitive function. As a result, a component of the adverse outcome from prematurity may relate to abnormal cerebellar development. This study proposes to use state-of-the-art magnetic resonance techniques to assess the metabolism and microstructure of the cerebellum during development in prematurely born neonates and to correlate that development with potentially treatable conditions in other organ systems of the baby and with two common conditions of the brain in prematurely born neonates: hemorrhage into the cerebral ventricles, and injury of the cerebral white matter. It is postulated that hemorrhage into the ventricular system and subarachnoid spaces around the cerebellum prevents the cerebellum from receiving important signals from the tissues that cover it, while injury to the cerebral white matter might interfere with signals sent to the cerebellum, thus contributing to cerebellar injury of the premature brain. Identification of the causative factors might allow those factors to be avoided or treated more aggressively, ultimately resulting in less cerebellar damage and improved clinical outcome. PROJECT/PERFORMANCE SITE (S) (if additional space is needed, use Project/Performance Site Format Page) Project/Performance Site Primary Location Organizational Name: University of California at San Francisco DUNS: 608379298 Street 1: 505 Parnassus Avenue Street 2: City: San Francisco State: CA Province: Country: USA Zip/Postal Code: 94143-0628 San Francisco County: Project/Performance Site Congressional Districts: Additional Project/Performance Site Location Organizational Name: DUNS: Street 1: Street 2: City: State: Province: Country: Zip/Postal Code: County: Project/Performance Site Congressional Districts:

Public Health Relevance

Brain injuries in prematurely born babies enormously increase the costs of health care during the first year of life. In addition, the poor neurodevelopmental outcome that results in poor school performance, and behavioral performance that results in decreased productivity of affected patients after childhood. This study aims to identify causes and, in that way, reduce the incidence of these injuries.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Developmental Brain Disorders Study Section (DBD)
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Babcock, Debra J
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Tymofiyeva, Olga; Ziv, Etay; Barkovich, A James et al. (2014) Brain without anatomy: construction and comparison of fully network-driven structural MRI connectomes. PLoS One 9:e96196
Tymofiyeva, O; Hess, C P; Xu, D et al. (2014) Structural MRI connectome in development: challenges of the changing brain. Br J Radiol 87:20140086
Tymofiyeva, Olga; Hess, Christopher P; Ziv, Etay et al. (2013) A DTI-based template-free cortical connectome study of brain maturation. PLoS One 8:e63310
Xu, Duan; Mukherjee, Pratik; Barkovich, A James (2013) Pediatric brain injury: can DTI scalars predict functional outcome? Pediatr Radiol 43:55-9
Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L et al. (2012) Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy. J Pediatr 161:88-93
Tam, Emily W Y; Rosenbluth, Glenn; Rogers, Elizabeth E et al. (2011) Cerebellar hemorrhage on magnetic resonance imaging in preterm newborns associated with abnormal neurologic outcome. J Pediatr 158:245-50
Tam, Emily W Y; Miller, Steven P; Studholme, Colin et al. (2011) Differential effects of intraventricular hemorrhage and white matter injury on preterm cerebellar growth. J Pediatr 158:366-71
Xu, Duan; Bonifacio, Sonia L; Charlton, Natalie N et al. (2011) MR spectroscopy of normative premature newborns. J Magn Reson Imaging 33:306-11
Barkovich, A James (2010) Current concepts of polymicrogyria. Neuroradiology 52:479-87
Xu, Duan; Vigneron, Daniel (2010) Magnetic resonance spectroscopy imaging of the newborn brain--a technical review. Semin Perinatol 34:20-7

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