Detection and Distinction of Mild Brain Injury Effects in a Ferret Model Using Diffusion Tensor MRI (DTI) and...

Area of Science:

• Neuroscience
• Radiology
• Biomedical Engineering

Background:

• Mild traumatic brain injury (mTBI) lacks sensitive research tools and robust pre-clinical models.
• Rodent models do not fully replicate human brain complexity, such as gyrencephalic cortices and high white matter volume.

Purpose of the Study:

• To develop and apply high-resolution diffusion tensor MRI (DTI) analysis in a ferret model of mTBI.
• To investigate DTI alterations and morphometric changes in ferret brains following mild controlled cortical impact (CCI).
• To compare findings with human mTBI studies and immunohistochemistry.

Main Methods:

• Diffusion tensor MRI (DTI) analysis on ex vivo adult male ferret brains (n=26) at various time points post-mild CCI.
• Optimized DTI analysis tools including template-based ROI analysis, lesion overlay mapping, and DTI-driven tensor-based morphometry (D-TBM).
• Qualitative comparison with immunohistochemistry for neurons, astrocytes, and microglia.

Main Results:

• Focal DTI abnormalities, including reduced cortical diffusivity, were observed in most injured brains.
• Reduced white matter fractional anisotropy (FA) was noted in the chronic period near the CCI site.
• Global white matter abnormalities, reduced diffusivity, and increasing atrophy were observed over time, becoming more bilateral.

Conclusions:

• The ferret model, with its human-like brain structure, effectively reveals focal white matter abnormalities in mTBI.
• DTI and morphometric findings in this model show overlap with human mTBI studies.
• Combining DTI tools with a human-similar model offers an advantageous approach for mTBI research.