MR Imaging of Perinatal Brain Injury

Sponsor

University of Pittsburgh (Other)

Overall Status

Recruiting

CT.gov ID

NCT02008045

Collaborator

(none)

300

Enrollment

Location

200

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to collect and compare information from cranial ultrasounds, magnetic resonance imaging scans, neurological exam and neuropsychological assessments of children. The investigators hope that the information collected in this study will help with early screening, diagnosis and treatment of brain injury in newborns as well as identify a connection between MR imaging (MRI-magnetic resonance imaging, MRS-magnetic resonance spectroscopy) and neurodevelopmental outcome.

Condition or Disease	Intervention/Treatment	Phase
Perinatal White Matter Brain Injury	Device: Magnetic Resonance Imaging Behavioral: Neurodevelopmental Testing

Detailed Description

In the last two decades, major advances have been made in the clinical care of premature and term infants, including in the management of sepsis and respiratory compromise that can contribute to neurological disabilities in survivors. The incidence of classic cystic periventricular leukomalacia (PVL) has declined and a more diffuse and non-cystic pattern of cerebral white matter injury is more predominant. Although multiple pathologies occur in premature infants, the principal variety accounting for the predominance of neurodevelopmental disability is PVL. This disability in very low birth weight infants (VLBW) (< 1500 grams) includes cognitive/behavioral deficits in 25-50% and cerebral palsy in 5-10%. Neuroimaging studies of VLBW survivors suggest that the cerebral palsy is related to the focal necrotic lesions of PVL, whereas the cognitive/behavioral deficits correlate with more diffuse cerebral white matter injury. PVL is defined as damaged immature cerebral white matter with periventricular focal necrosis ("focal" component) in association with diffuse reactive gliosis and microglial activation in the surrounding white matter ("diffuse" component). Of note, PVL occurs in the late preterm infant and the term infant, particularly in cases of congenital heart disease. The pathogenesis of perinatal white matter injury is currently thought to be related to a complex interaction between maternal/fetal infection, cytokines and hypoxia-ischemia which results in both the generation of reactive oxygen specific agents (oxidative stress), apoptotic oligodendrocyte cell death, and axonal injury. In long-term survivors with PVL, neuroimaging studies often demonstrate reduced cerebral white matter volume, impaired myelination, ventriculomegaly and reduced volume in the cerebral cortex, thalamus/basal ganglia and cerebellum. In many of these long-term studies, the preterm children studies had normal cranial ultrasound. Cranial ultrasound, however, is not adequate for assessing non-cystic focal or diffuse white matter injury. To date, there are no longitudinal MR studies of preterm or congenital heart disease infants which correlate advanced neonatal MR imaging techniques with long-term neurodevelopmental outcome or advanced MR techniques performed in the childhood period.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Advanced MR Imaging of Perinatal Brain Injury: Correlation With Neurocognitive Outcome

Study Start Date :

Apr 1, 2009

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Neonates at Risk for Brian Injury Magnetic Resonance Imaging Neurodevelopmental Testing - 18 Month	Device: Magnetic Resonance Imaging Brain MRI without Contrast Behavioral: Neurodevelopmental Testing Validated battery of neurodevelopmental and psychological tests.
Term Neonates Magnetic Resonance Imaging Neurodevelopmental Testing - 18 Month	Device: Magnetic Resonance Imaging Brain MRI without Contrast Behavioral: Neurodevelopmental Testing Validated battery of neurodevelopmental and psychological tests.

Arm

Intervention/Treatment

Neonates at Risk for Brian Injury

Magnetic Resonance Imaging Neurodevelopmental Testing - 18 Month

Device: Magnetic Resonance Imaging

Brain MRI without Contrast

Behavioral: Neurodevelopmental Testing

Validated battery of neurodevelopmental and psychological tests.

Term Neonates

Magnetic Resonance Imaging Neurodevelopmental Testing - 18 Month

Device: Magnetic Resonance Imaging

Brain MRI without Contrast

Behavioral: Neurodevelopmental Testing

Validated battery of neurodevelopmental and psychological tests.

Outcome Measures

Primary Outcome Measures

Developmental Assessment [18 Months]
Administration of neurodevelopmental testing and completion of parent questionnaires regarding the child's development.

Secondary Outcome Measures

Assessment of White Matter Injury in Brain [Baseline]
MR Scan
Changes in White Matter Injury from Baseline [at 6 Years]
MR Scan

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 7 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Preterm babies and neonates with congenital heart disease
Term Neonates

Exclusion Criteria:

Severe congenital brain malformation
Significant chromosomal abnormality / syndrome which could confound the neurodevelopmental follow up data
Preterm birth and congenital heart disease
Focal neurological abnormality
Chronic seizures
Severe congenital brain malformation
Significant chromosomal abnormality/ syndrome which could confound the neurodevelopmental follow up data
Major pregnancy complication (diabetes, eclampsia)
Sepsis
ECMO
Significant birth trauma and/or hypoxic ischemic injury