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Updated: May 7, 2026
Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Imaging neurodegeneration in the mouse hippocampus after neonatal hypoxia-ischemia using oscillating gradient
Manisha Aggarwal1, Jennifer Burnsed, Lee J Martin
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Purpose:
To investigate if frequency-dependent contrasts using oscillating gradient diffusion MRI (dMRI) can detect hypoxia-ischemia (HI) -induced neurodegeneration in the neonatal mouse hippocampus.
Methods:
Pulsed- and oscillating-gradient dMR images (at 50, 100, and 150 Hz) were acquired from postmortem fixed brains of mice exposed to neonatal HI using the Rice-Vanucci model. MRI data were acquired at 1, 4, and 8 days following HI, and compared with histological data from the same mice for in situ histological validation of the MRI findings.
Results:
The rate of change of apparent diffusion coefficient with gradient frequency (Δf ADC) revealed unique layer-specific contrasts in the neonatal mouse hippocampus. Δf ADC measurements were found to show a significant decrease in response to neonatal HI injury, in the pyramidal (Py) and granule (GrDG) cell layers compared with contralateral regions. The areas of reduced intensity in the Δf ADC maps corresponded to regional neurodegeneration seen with H&E and Fluoro-Jade C stainings, indicating that alterations in Δf ADC contrasts are sensitive to early microstructural changes due to HI-induced neurodegeneration in the studied regions.
Conclusion:
The findings show that the frequency-dependence of ADC measurements with oscillating-gradient dMRI can provide a sensitive contrast to detect HI-induced neurodegeneration in neuronal layers of the neonatal mouse hippocampus.
Insights
Frequency-dependent diffusion MRI (dMRI) effectively detects hypoxia-ischemia (HI) induced neurodegeneration in neonatal mouse hippocampus. This technique reveals layer-specific microstructural changes, aiding in early diagnosis of brain injury.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Developmental Neuroscience
Background:
- Neonatal hypoxia-ischemia (HI) is a significant cause of brain injury.
- Early detection of neurodegeneration is crucial for timely intervention.
- Diffusion MRI (dMRI) is a powerful tool for assessing brain microstructure.
Purpose of the Study:
- To evaluate the utility of frequency-dependent contrasts in oscillating-gradient dMRI for detecting HI-induced neurodegeneration.
- To investigate layer-specific changes in the neonatal mouse hippocampus following HI.
- To validate dMRI findings with histological assessments.
Main Methods:
- Acquisition of pulsed- and oscillating-gradient dMRI data from postmortem fixed neonatal mouse brains.
- Utilized varying gradient frequencies (50, 100, 150 Hz) to generate frequency-dependent contrasts.
- Compared dMRI data with H&E and Fluoro-Jade C staining for histological validation.
Main Results:
- Frequency-dependent ADC (Δf ADC) measurements revealed unique layer-specific contrasts in the hippocampus.
- A significant decrease in Δf ADC was observed in pyramidal and granule cell layers post-HI.
- Reduced Δf ADC intensities correlated with observed regional neurodegeneration.
Conclusions:
- Oscillating-gradient dMRI provides sensitive, frequency-dependent contrasts for detecting neurodegeneration.
- This technique can identify HI-induced microstructural changes in specific neuronal layers.
- Frequency-dependent dMRI holds promise for early detection of neonatal brain injury.
