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Published on: October 21, 2017
Diffusion characteristics associated with neuronal injury and glial activation following hypoxia-ischemia in the
Gregory A Lodygensky1, Tim West, Matthew D Moravec
1Division of Pediatric and Neonatal Intensive Care, University Hospital of Geneva, Geneva, Switzerland. gregory.lodygensky@unige.ch
Abstract:
To identify quantitative MRI indices of injury in the brain following neonatal hypoxic-ischemic brain injury, we subjected mouse pups to hypoxia-ischemia on postnatal day 7 and obtained conventional and diffusion-weighted in vivo images of the brain 24 h later followed by histological assessment. T(2)-weighted images showed increased signal intensity in the CA1 and CA2 regions of the hippocampus ipsilateral to the injury and adjacent white matter. In contrast, diffusion imaging showed reduced apparent diffusion coefficient (ADC) values in CA1 and CA2, but increased values in the adjacent white matter. Histological analysis showed widespread gliosis with degenerating oligodendrocytes in the ipsilateral hippocampus. In addition, white matter areas that were abnormal by MRI showed an increase in the number of activated microglia (CD45 positive cells). Activated caspase-3 immunostaining showed a marked increase in neurons in the hippocampal regions corresponding to those with reduced ADC, and a quantitative measure of staining showed a statistically significant correlation with the ADC. In contrast, ADC was higher in adjacent white matter, where histology showed activation of microglia and reactive oligodendrocytes but not caspase-3 activation. These results suggest that the ADC response differs between areas of neuronal injury as compared with those showing glial changes without marked cell death.
Insights
Quantitative MRI can detect brain injury in newborns after hypoxic-ischemic events. Apparent diffusion coefficient (ADC) MRI values reveal distinct patterns in neuronal versus glial injury, aiding diagnosis.
Area of Science:
- Neuroscience
- Radiology
- Neonatal Research
Background:
- Neonatal hypoxic-ischemic brain injury (HIBI) is a major cause of neurological disability.
- Accurate and early detection of HIBI is crucial for timely intervention.
- Conventional MRI has limitations in quantifying subtle brain injury.
Purpose of the Study:
- To identify quantitative magnetic resonance imaging (MRI) indices for detecting brain injury following neonatal HIBI.
- To differentiate between neuronal and glial injury patterns using MRI.
- To correlate MRI findings with histological assessments in a neonatal HIBI mouse model.
Main Methods:
- Neonatal mouse pups underwent hypoxic-ischemia (HI) on postnatal day 7.
- Conventional T2-weighted and diffusion-weighted MRI were acquired 24 hours post-HI.
- Histological analysis included markers for neuronal death (caspase-3) and glial activation (CD45, oligodendrocytes).
Main Results:
- T2-weighted MRI showed abnormalities in the hippocampus (CA1, CA2) and adjacent white matter.
- Diffusion imaging revealed reduced apparent diffusion coefficient (ADC) in hippocampal regions with neuronal injury (caspase-3 positive).
- Increased ADC was observed in white matter areas with glial activation (microglia, reactive oligodendrocytes) but without significant neuronal death.
Conclusions:
- Apparent diffusion coefficient (ADC) MRI values show distinct responses in neuronal versus glial injury following neonatal HIBI.
- Quantitative diffusion MRI can differentiate injury types, offering potential for improved diagnosis and monitoring.
- MRI-based indices may provide valuable insights into the pathophysiology of HIBI.
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