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
Panigrahy, Ashok; Lee, Vincent; Ceschin, Rafael et al. (2016) Brain Dysplasia Associated with Ciliary Dysfunction in Infants with Congenital Heart Disease. J Pediatr 178:141-148.e1
Lao, Yi; Wang, Yalin; Shi, Jie et al. (2016) Thalamic alterations in preterm neonates and their relation to ventral striatum disturbances revealed by a combined shape and pose analysis. Brain Struct Funct 221:487-506
Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung et al. (2015) Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity. Neuroreport 26:22-6
Paquette, Lisa B; Votava-Smith, Jodie K; Ceschin, Rafael et al. (2015) Abnormal development of thalamic microstructure in premature neonates with congenital heart disease. Pediatr Cardiol 36:960-9
Watchko, Jon F; Painter, Michael J; Panigrahy, Ashok (2015) Are the neuromotor disabilities of bilirubin-induced neurologic dysfunction disorders related to the cerebellum and its connections? Semin Fetal Neonatal Med 20:47-51
Panigrahy, Ashok; Schmithorst, Vincent J; Wisnowski, Jessica L et al. (2015) Relationship of white matter network topology and cognitive outcome in adolescents with d-transposition of the great arteries. Neuroimage Clin 7:438-48
Wisnowski, Jessica L; Ceschin, Rafael C; Choi, So Young et al. (2015) Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury. Neuroradiology 57:515-25
Ceschin, Rafael; Wisnowski, Jessica L; Paquette, Lisa B et al. (2015) Developmental synergy between thalamic structure and interhemispheric connectivity in the visual system of preterm infants. Neuroimage Clin 8:462-72
Ceschin, Rafael; Lee, Vince K; Schmithorst, Vince et al. (2015) Regional vulnerability of longitudinal cortical association connectivity: Associated with structural network topology alterations in preterm children with cerebral palsy. Neuroimage Clin 9:322-37
Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung et al. (2015) Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex. PLoS One 10:e0130686

Showing the most recent 10 out of 24 publications