Perinatal brain injury is a significant problem given the high incidence of prematurity in the United States, with an estimated increase of 28% over the past 20 years. It is now estimated that up to 40% of survivorsof perinatal brain injury are compromised neurologically, including motor deficits, learning and behavioral problems. Our overall hypothesis is that magnetic resonance spectroscopy (MRS) may be a biomarker of the diffuse component of perinatal white matter injury and that altered neonatal NAA and NAA/myo-inositol ratio will correlate with long term neurodevelopmental outcome and thalamo-cortical abnormalities as assessed with advanced MR techniques at 6 years of age. We will specifically focus on premature infants at term equivalent age and term infants with congenital heart disease (transposition of the great arteries and single ventricle physiology).
Our specific aims are:
Aim 1 : Determine "normative levels" of absolute concentration of NAA and myo-inositol in neonatal cerebral white matter using a longitudinal study design by (1a) performing MRS in term infants with no risk factors for perinatal white matter injury;(1b) performing longitudinal neurodevelopmental assessment at 18 months, 36 months and 6 years of age;(1c) performing DTI and VM MR imaging at 6 yrs of age.
Aim 2 : To determine the levels of absolute concentration of NAA and myo-inositol in the cerebral white matter using a longitudinal study design by (2a) performing MRS in term equivalent premature infants (2b) performing longitudinal neurodevelopmental assessment at 18 months, 36 months and 6 years of age (2c) performing DTI and VM MR imaging at 6 yrs of age.
Aim 3 : To determine the levels of absolute concentration of NAA and myo-inositol in the cerebral white matter using a longitudinal study design by (3a) performing MRS in term infants with congenital heart disease (3b) performing longitudinal neurodevelopmental assessment at 18 months, 36 months and 6 years of age (3c) performing DTI and VM MR imaging at 6 yrs of age. As part of the career plan, the applicant will obtain skills in (1) advanced MR imaging techniques (2) clinical research outcome, advanced statistics and clinical management skills, and (3) neonatal neuropathology, pediatric neurology and pediatric neuro-psychology.

Public Health Relevance

This longitudinally designed study , using both advanced MR imaging and neurocognitive testing, will allow us to study the effects of perinatal white matter injury on long term neurodevelopmental function and thalamo-cortical structural plasticity in childhood. This project will help identify neonates with perinatal white matter injury at high risk for developing poor neurodevelopmental outcome for early intervention services.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS063371-06
Application #
8431807
Study Section
NST-2 Subcommittee (NST)
Program Officer
Hicks, Ramona R
Project Start
2009-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
6
Fiscal Year
2013
Total Cost
$185,493
Indirect Cost
$12,865
Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Wisnowski, Jessica L; Panigrahy, Ashok; Painter, Michael J et al. (2014) Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise. Semin Perinatol 38:422-8
Imagawa, Karen Kay; Hamilton, Anita; Ceschin, Rafeal et al. (2014) Characterization of microstructural injury: a novel approach in infant abusive head trauma-initial experience. J Neurotrauma 31:1632-8
Degnan, Andrew J; Ceschin, Rafael; Lee, Vince et al. (2014) Early metabolic development of posteromedial cortex and thalamus in humans analyzed via in vivo quantitative magnetic resonance spectroscopy. J Comp Neurol 522:3717-32
Wisnowski, Jessica L; Schmithorst, Vincent J; Rosser, Tena et al. (2014) Magnetic resonance spectroscopy markers of axons and astrogliosis in relation to specific features of white matter injury in preterm infants. Neuroradiology 56:771-9
Blüml, Stefan; Wisnowski, Jessica L; Nelson Jr, Marvin D et al. (2014) Metabolic maturation of white matter is altered in preterm infants. PLoS One 9:e85829
Wisnowski, Jessica L; Bluml, Stefan; Paquette, Lisa et al. (2013) Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants. PLoS One 8:e56880
Shi, Jie; Wang, Yalin; Ceschin, Rafael et al. (2013) A multivariate surface-based analysis of the putamen in premature newborns: regional differences within the ventral striatum. PLoS One 8:e66736
Paquette, L B; Wisnowski, J L; Ceschin, R et al. (2013) Abnormal cerebral microstructure in premature neonates with congenital heart disease. AJNR Am J Neuroradiol 34:2026-33
Panigrahy, Ashok; Wisnowski, Jessica L; Furtado, Andre et al. (2012) Neuroimaging biomarkers of preterm brain injury: toward developing the preterm connectome. Pediatr Radiol 42 Suppl 1:S33-61
Nagasunder, A C; Kinney, H C; Blüml, S et al. (2011) Abnormal microstructure of the atrophic thalamus in preterm survivors with periventricular leukomalacia. AJNR Am J Neuroradiol 32:185-91

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