This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The increase in premature births in Maryland over the last decade poses significant health problems for those children with brain injury associated with prematurity. While dramatic advances in neonatal care have led to remarkable improvements in intact survival, a significant subgroup are left with injury to brain white matter (WM) pathways and later childhood neurodevelopmental disorders, including cerebral palsy and mental retardation. Despite a wide range of accepted medical and rehabilitative interventions for these children, there is often incomplete understanding of etiology and variability in treatment effect and outcome. A number of newly developed neuroimaging techniques have been utilized to address these problems, including magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). DTI, which uses directionality of water diffusion to identify central white matter (WM) tracks, improves visualization of brain maldevelopment and injury. In the proposed study, we will use both MRI and DTI to classify cerebral WM injury in 30 children with cerebral palsy born prematurely. Children between the ages of 4- 8 years who have a clinical indication for a MRI will be recruited from the Kennedy Krieger Institutes Phelps Center for Cerebral Palsy to participate in this study. Utilizing a stratified sampling design to enhance representativeness in prematurity and white matter maturation, 10 children in each of three gestational age groups: <28 weeks, 28-32 weeks, and 33-36 weeks will be enrolled. In addition to conventional MRI, DTI will be used to: 1) delineate variability in white matter (WM) injury across sensory and motor tracts and 2) correlate tract abnormalities with standardized motor and sensory test outcomes. Utilizing a semiquantitative DTI WM tract classification system developed in a previous study, 25 WM structures acquired on DTI imaging will be graded. Volumetric analysis of brain MRI data will be quantified as an independent marker of the severity of WM injury. Measures of WM injury obtained using both DTI and MRI techniques will be compared. Validated clinical scales will be utilized to assess the primary outcome measures- strength, spasticity, dystonia, and vibration threshold. Findings from this study will be used to design a multisite study investigating etiological antecedents, white matter injury and sensorimotor outcomes in a larger population of premature children with cerebral palsy. The long-term goal of this research is to further refine cerebral palsy diagnosis and classification, serving to develop interventions for cerebral white matter injury prevention as well as rehabilitation.
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