Characterizing the FASD cerebral cortex in utero with DTI

Research project

Description

DESCRIPTION (provided by applicant): Fetal exposure to alcohol leads to a wide range of neurological deficits collectively termed fetal alcohol spectrum disorders (FASD). The CDC estimates that FASD currently affects as many as 4.5 out of every 1000 births within the United States. Existing intervention strategies can improve the quality of life in affected individuals, provided they are initiated at the earliest age possible. Unfortunately, early FASD diagnosis is difficult, partly because behavioral manifestations of the disorder are not apparent until childhood. We propose to develop a magnetic resonance imaging (MRI)-based strategy to detect cellular-level morphological alterations in the developing cerebral cortex. Nonhuman primate research subjects will be bred after being trained to drink 1.5 g/kg/day of ethanol, or an isocaloric amount of maltose/dextrin solution. Animals will continue to drink throughout the first 60 days of pregnancy, after which access to ethanol will be terminated. Fetal brain T2-weighted and diffusion tensor imaging (DTI) data will be acquired on 3 groups of ethanol or maltose/dextrin animals: group 1 will be scanned on gestational day (G)85, group 2 on G110, and group 3 on G135. Immediately after MRI, fetuses will be delivered by cesarian section and brains will be prepared for histological processing. The first aim for this experiment is to characterize the effects of early ethanol exposure on cerebral cortical thickness, surface area, and water diffusion anisotropy over the period ranging from G85 to G135. The second aim is to validate the cortical thickness effects of ethanol exposure using unbiased stereological techniques, and to characterize the biological source of the neuroimaging observations. The latter will be accomplished by determining cerebral cortical cell numbers, measuring the volume fraction of the neuropil, and quantifying morphological complexity of cortical neuronal axonal and dendritic arbors. This work will provide an objective strategy for characterizing the effects o early ethanol exposure on subsequent development of the cerebral cortex, which will facilitate earlier detection of FASD that is currently achievable.
StatusFinished
Effective start/end date12/20/1211/30/17

Funding

  • National Institutes of Health: $522,961.00
  • National Institutes of Health: $519,726.00
  • National Institutes of Health: $539,417.00
  • National Institutes of Health: $409,454.00

Fingerprint

Fetal Alcohol Spectrum Disorders
Diffusion Tensor Imaging
Cerebral Cortex
Ethanol
Maltose
Magnetic Resonance Imaging
Brain
Research Subjects
Neuropil
Anisotropy
Centers for Disease Control and Prevention (U.S.)
Neuroimaging
Cesarean Section
Primates
Fetus
Cell Count
Alcohols
Quality of Life
Parturition
Pregnancy

Keywords

  • Medicine(all)