Open Access Dissertation
Date of Award
John M. Cavanaugh
Diffuse axonal injury, also known as traumatic axonal injury (TAI), is a major contributor to the pathology of traumatic brain injury. However, TAI is undetectable to conventional clinical magnetic resonance (MR) imaging techniques. Histologically, TAI is characterized by swollen axons that eventually disconnect and form axonal retraction balls (RB) in various white matter tracts. MR-diffusion tensor imaging (MR-DTI) has been reported to be sensitive to TAI in human TBI patients by measuring water molecular diffusion motion in white matter fiber tracts. To date, only one correlative animal study has been carried out to investigate the DTI relationship to TAI, and it has reported a relationship between DTI changes and TAI. No other animal study has validated the correlation between DTI and TAI. Therefore, this study is the second animal study that has examinedthe correlation between histological observations of axonal damage in white mater tract and the DTI measurements over time.
TAI was induced in twenty-four anaesthetized male Sprague Dawley rats utilizing an impact acceleration device (Marmarou et al 1994). T2 weighted MR images, and DTI images were acquired in vivo pre-impact, and four hours, twenty-four hours, three days and seven days post-impact. The DTI images were obtained in a Bruker 4.7 Tesla scanner in six gradient directions. Fractional anisotropy (FA), diffusion trace, axial diffusivity (AD) and radial diffusivity (RD) were calculated by using DTI Studio (Johns Hopkins University). After imaging, perfused brain tissue was processed for &beta-amyloid precursor protein (&beta-APP) and RMO14 immunocytochemistry and quantified by ImageJ software (NIH) for each time point.
&beta-APP and RMO14 immunoreactive axons were observed in optic chiasm (Och) and corpus callosum (CC). TAI was more prevalent and less variable in the Och in comparison to CC. In the Och and CC &beta-APP positive axons were more prominent at eight hours and twenty-eight hours post-TBI and decreased as time elapsed. In the Och and CC RMO14 positive axons were more prominent at twenty-eight hours post-TBI and decreased as time elapsed. However, at seven days post-TBI a modest increase of RMO14 positive axons occurred in comparison to three days post TBI.
The mean FA values of the DTI image of the Och and CC revealed a decrease of FA at four hours post-TBI (p<0.05). After four hours post-TBI the FA value increased and remained increased up to seven days post-TBI in the CC and Och. The other DTI parameters also changed over time.
No linear relationship was found between FA and TAI density and between AD and TAI density in the CC and Och. The diffusion trace was found to be correlated with TAI density at four hours and seven day post-TBI in the Och and CC respectively. The RD was found to be correlated with TAI density at four hours and seven days post-TBI in the Och.
This study was unable to verify that the DTI changes after TBI are an indication of TAI. However, the DTI parameters did change as time elapsed after TBI. The profile of the DTI parameter changes may be an indication of edema. In addition, other imaging parameters, diffusion trace and RD, did show correlation with the density &beta-APP positive axons and may be the better DTI parameters for describing axonal integrity such as axonal permeability.
Zakaria, Nisrine, "Comparison of progression of diffuse axonal injury with histology and diffusion tensor imaging" (2011). Wayne State University Dissertations. 341.