RESEARCH PROJECT THE VULNERABLE PRETERM CEREBELLUM: ELUCIDATING MECHANISMS AND CONSEQUENCES OF INJURY Catherine Limperopoulos, Ph.D., Project Director Director, MRI Research of the Developing Brain Director, Advanced Pediatric Brain Imaging Research Laboratory Diagnostic Imaging and Radiology Children?s National Health System Louis-Gilbert Vzina, Ph.D. Director, Pediatric Neuroradiology Children?s National Health System Adre J. du Plessis, MBchB, MPH Chief, Fetal and Transitional Medicine Children National Health System Penny Glass, Ph.D. Director, Child Development Center Center for Neuroscience and Behavioral Medicine Children?s National Health System Lauren Kenworthy, Ph.D. Pediatric Neuropsychologist Director, Center for Autism Spectrum Disorders Children?s National Health System Zungho (Wesley) Zun, Ph.D. MRI Physicist/Research Faculty Advanced Pediatric Brain Imaging Research Laboratory Children?s National Health System Robert J. McCarter Jr., ScD Director of the IDDRC Biostatistics and Informatics Component Head: Research Section of Study Design and Biostatistical Consulting Children?s National Health System Catherine Stoodley, D.Phil. Assistant Professor Psychology and Neuroscience Department American University Abstract Premature birth is a major public health problem, associated with a personal, familial, and societal burden of enormous proportions. The potentially lifelong cognitive, learning and affective-behavioral consequences have become the major determinant of life quality in prematurity survivors, with up to 50% of very premature infants experiencing dysfunction in these domains by school age. Impaired cerebellar development has been recently implicated in this dysfunction. We have described a clinically important, previously under-recognized form of prematurity-related cerebellar parenchymal injury in up to 20% in extremely preterm infants. Recently, our observations have extended beyond the role of parenchymal cerebellar injury to a broader and more prevalent spectrum of cerebellar developmental impairments. We have shown that cerebellar development is (i) markedly accelerated during the third trimester, but (ii) significantly impeded after premature birth, even in the absence of direct cerebellar injury. We refer to this impaired growth as cerebellar developmental impairment (CDI). Complementing this intriguing set of structural observations are our findings of a distinctive long-term neuropsychological profile of cognitive, language, affective and social deficiency, which we have termed the developmental cerebellar cognitive affective disorder. The onset and underlying mechanisms and consequences of prematurity-related CDI remain poorly understood, which in turn have complicated the search for potential therapeutic interventions. We propose to utilize serial, advanced MRI techniques to elucidate the timing, evolution, mechanisms and risk factors of CDI in preterm infants born ?30 weeks gestational age. Our overarching goal is to identify early MR imaging biomarkers of prematurity-related CDI and the associated clinical factors that lead to specific development disabilities. We plan to leverage our large fetal normative database to compare in-utero fetal and ex-utero preterm cerebellar growth trajectories. These findings will inform specific targets, interventions and timing of future neuroprotective strategies, advance clinical practices, and improve neurodevelopmental outcomes.

Public Health Relevance

The Vulnerable Preterm Cerebellum: Elucidating Mechanisms and Consequences of Injury PI: Catherine Limperopoulos, PhD Cerebellar injury has been implicated in the high prevalence of neurodevelopmental disabilities in very premature infants. The goal of this study is to identify early magnetic resonance imaging biomarkers of prematurity-related cerebellar developmental impairment that leads to specific development disabilities. Findings will inform specific targets for future interventions to improve neurodevelopmental outcomes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54HD090257-01
Application #
9229292
Study Section
Special Emphasis Panel (ZHD1-DSR-H (50))
Project Start
Project End
Budget Start
2016-09-01
Budget End
2017-05-31
Support Year
1
Fiscal Year
2016
Total Cost
$30,267
Indirect Cost
$12,971
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
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