Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Hope Center for Neurological Disorders, Washington University in St. Louis, San Luis, Missouri, United States
Experimental Neurology (Impact Factor: 4.7). 06/2007; 205(1):116-31. DOI: 10.1016/j.expneurol.2007.01.035
Source: PubMed


Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 h and 24 h post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters--axial diffusivity and relative anisotropy--were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose.

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    • "s a disorder of brain connectivity 7 however , given that the role of primary and secondary injury processes will vary at different times post - injury and that there is as of yet no comprehensive model of TBI - associated diffusion changes over time . Changes in DTI metrics can be interpreted with reference to animal models of TBI ( e . g . , Mac Donald et al . , 2007 ) , but the time frame of pathophysiological responses in humans may not directly map onto that seen in animals . Additionally , given the known limitations in char - acterizing white matter in complex regions where fibers intersect , interpretation of longitudinal changes in such regions can be especially difficult . For instance , an "
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    ABSTRACT: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. TBI has a negative impact on distributed brain networks that lead to behavioral disturbance.
    Journal of the International Neuropsychological Society 11/2015; in press. · 2.96 Impact Factor
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    • "Chronic tissue alterations appear in the posterior part of the brain . A spatial gradient in the white matter ( Mac Donald et al . , 2007a ) , and the effect of the severity of the injury ( Rutgers et al . , 2008 ; Hylin et al . , 2013 ) or position of the impact ( Flygt et al . , 2013 ) were previously investigated . Most studies using LFP injury focus on the acute and / or subacute phases , from a few hours to several days / weeks after injury ( Graham et al . , 2000 ; F"
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    Frontiers in Neuroscience 04/2015; 9:128. DOI:10.3389/fnins.2015.00128 · 3.66 Impact Factor
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    • "ative correlation between relative anisotropy ( RA ) ( similar to FA ) to the density of beta - APP immunohistochemical staining at the acute stage ( within 24 h after injury ) ( Mac Donald et al . , 2007b ) . This suggests that axonal disruption and breakdown of axonal cytoskeleton structure are the major pathology of TAI at the acute stage ( Mac Donald et al . , 2007b ) . Over 4 weeks after injury , the RA remains decreased with axial diffusivity " pseudo - normalized " and radial diffusivity increased , confirmed by histology of demyelination , edema , neurofilament compac - tion as well as axonal disruption ( Mac Donald et al . , 2007a ) ."
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