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Updated: Jan 9, 2026
Development of an Uncomplicated Mild Traumatic Brain Injury Model Modified by Weight-Drop Method and Evidenced by Magnetic Resonance Imaging
Published on: April 11, 2025
MRI investigation of orientation-dependent changes in microstructure and function in a mouse model of mild traumatic
Amr Eed1,2, Jake Hamilton1,2, Xiaoyun Xu3,4
1Centre for Functional and Metabolic Mapping (CFMM), Robarts Research Institute, Western University, London, Canada.
Abstract:
While neuroimaging studies have revealed notable white matter damage following mild traumatic brain injury (mTBI), the specific tracts and brain regions affected vary widely across studies. Here, we explored whether the spatial orientation of white matter tracts influences susceptibility to repeated mTBI, predicting that tracts oriented orthogonal to the axis of rotation of the head during impact (within the plane of rotation) would exhibit the most damage. Using a model of repeated rotational mTBI in mice, we acquired advanced diffusion MRI (diffusional kurtosis imaging using oscillating gradient encoding) and resting-state functional MRI (fMRI) data at baseline and 1-week post-injury. Consistent with our prediction, while both diffusivity and diffusional kurtosis decreased in the white matter of injured mice, only diffusional kurtosis revealed microstructural changes confined to tracts oriented orthogonal to the right-left axis of rotation. In addition, both region and subregion analyses showed functional connectivity (FC) deficits between regions connected via tracts running orthogonal to the rotation axis. The orientation-dependent changes in imaging metrics were validated by histopathological analyses. Females showed greater microstructural changes than males using diffusion MRI following injury, while no sex differences were detected by fMRI. Interestingly, the region-specific and subregion-specific FC analyses showed overlapping but non-identical changes in FC suggesting the utility of using both coarse and fine levels of brain parcellation for FC analyses in mTBI. These findings suggest that mTBI imaging studies may benefit from the consideration that damage after mTBI will predominate in tracts that are oriented orthogonal to the axis of rotation produced by the impact and that diffusivity and diffusional kurtosis as well as region and subregion-specific fMRI analyses can detect these changes.
Insights
White matter tract orientation influences mild traumatic brain injury (mTBI) damage. Tracts orthogonal to the rotation axis showed the most microstructural and functional connectivity changes after repeated mTBI in mice.
Area of Science:
- Neuroscience
- Radiology
- Pathology
Background:
- Mild traumatic brain injury (mTBI) causes white matter damage, but affected areas vary.
- The influence of white matter tract orientation on mTBI susceptibility is not well understood.
Purpose of the Study:
- To investigate if white matter tract orientation affects susceptibility to repeated mTBI.
- To predict that tracts oriented orthogonal to the head's rotation axis would show the most damage.
Main Methods:
- Used a mouse model of repeated rotational mTBI.
- Acquired advanced diffusion MRI (diffusional kurtosis imaging) and resting-state fMRI data.
- Validated imaging findings with histopathology.
Main Results:
- Diffusional kurtosis revealed microstructural changes in tracts orthogonal to the rotation axis.
- Functional connectivity deficits were observed in regions connected by these tracts.
- Females exhibited greater microstructural changes than males on diffusion MRI.
Conclusions:
- mTBI damage is predominant in white matter tracts oriented orthogonal to the impact's rotation axis.
- Diffusion MRI (diffusivity and diffusional kurtosis) and fMRI can detect these orientation-dependent changes.
- Region and subregion fMRI analyses offer complementary insights into mTBI-related functional connectivity alterations.
