Neonatal encephalopathy and associated brain injury is a serious problem that results in an estimated 1 million annual neonatal deaths despite major advances in obstetrics and neonatal care. Recent studies have shown that cooling babies who suffer neonatal brain injury to 33.5? C for 72 hours, a process known as Therapeutic Hypothermia (TH), can markedly reduce brain injury in about 50% of affected babies. However, it appears to be more effective in neonates who have a sentinel event at the time of birth and basal ganglia injury on MRI than in those with intervascular boundary zone (""""""""watershed"""""""") injury identified on MRI. Neither the exact mechanisms by which TH reduces brain injury nor the reasons that the treatment is effective in some babies but not others are understood. It is known that neonatal brain injuries have a mixture of characteristics and, probably different mechanisms. Therefore, different treatments might eventually be tailored to individual babies based upon the type of injury and response to initial therapy. This study proposes to use techniques involving magnetic resonance imaging, called diffusion tensor imaging (DTI) and proton MR spectroscopy (MRS) in the neonatal period to assess which types of injury respond best to TH. A later MRI study at age 6 months from this cohort will use more sophisticated methods to evaluate how severe the injury was and how well the body was able to repair the injury with the help of TH as compared to prior studies without TH. Finally, MRI scans will be obtained at ages of 8-10 years from patients that were enrolled in an earlier study. Children who had very similar injuries will be grouped together and the MRI results will be used to see what MRI characteristics (using the more sophisticated MRI methods) are found in the children who recovered best from their injury but not in those who did not recover well. These MRI characteristics will be designated as """"""""markers of brain repair"""""""" after neonatal injury. Knowledge of these markers will help to more quickly evaluate new therapeutic interventions being used to increase repair after neonatal brain injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of California San Francisco
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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
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
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
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
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
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
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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