TY - JOUR
T1 - Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury
AU - Mac Donald, C. L.
AU - Dikranian, K.
AU - Song, S. K.
AU - Bayly, P. V.
AU - Holtzman, D. M.
AU - Brody, D. L.
N1 - Funding Information:
The study was funded in part by NIH RO1 NS047592 (SKS), NIH NS049237 (DLB), NIH P01 NS032636 (PVB), NIH R21 NS45237 (PVB) and a Burroughs Wellcome Career Award in the Biomedical Sciences (DLB). We would like to thank Dr. Jeff Neil, Dr. Kurt Thoroughman, and Dr. Joong Hee Kim for insightful discussions regarding the manuscript and Mrs. Maia Parsadanian for immunocytochemistry instruction.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Amyloid precursor protein
KW - Anisotropy
KW - Controlled cortical impact
KW - Diffuse axonal injury
KW - Diffusion tensor imaging
KW - Magnetic resonance imaging
KW - Stereology
KW - Traumatic axonal injury
KW - Traumatic brain injury
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=34247368915&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2007.01.035
DO - 10.1016/j.expneurol.2007.01.035
M3 - Article
C2 - 17368446
AN - SCOPUS:34247368915
SN - 0014-4886
VL - 205
SP - 116
EP - 131
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -