Quantitative evaluation of microscopic injury with diffusion tensor imaging in a rat model of diffuse axonal injury

Abstract

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and contributes significantly to neurological deficits. However, it is difficult to diagnose or characterize non-invasively with conventional imaging. Our study provides significant validation of a visual and statistical diffusion tensor imaging (DTI) technique as compared with pathological and electron microscopic study in a rat DAI model at multiple predilection sites and time points following trauma. Two DTI parameters, fractional anisotropy (FA) and axial diffusivity (AD), were significantly reduced from 12 h to 5 days post-trauma, corresponding to pathological axonal injury. At 7 days post-trauma, FA remained decreased, whereas AD pseudo-normalized and radial diffusivity increased. The temporal alterations in DTI parameters were observed in multiple predilection sites, and the extent of the changes in these parameters correlated significantly with the severity of histologically visualized axonal injury, as assessed by integrated optical density of immunochemically stained injured axons with quantitative stereology. Although anatomical T2-weighted magnetic resonance images showed no abnormal signals in microscopic lesions, we detected and characterized axonal injury directly by DTI at each time point. These results demonstrate that DTI has significant potential as a non-invasive tool with which to quantitatively diagnose and evaluate microstructural injury in the experimental and clinical assessment of DAI. This method can assist in accurate evaluation of the extent of axonal injury, detection of severe predilection foci, determination of approximate time of injury, and monitoring of the pathogenic condition at the early post-injury stage.

Radiological–pathological correlation of diffusion tensor and magnetization transfer imaging in a closed head traumatic brain injury model

“…8–10 Interpretation of DTI metrics in TBI patients are controversial with some studies indicating “reduced” fractional anisotropy (FA) and “elevated” mean diffusivity (MD) in white matter on DTI, 6, 11 while others report “increased” FA and “decreased” MD. 7, 12, 13 Reasons for these confounding results partly originate from using cross-sectional studies at single time points to draw conclusions about DTI metrics at potentially disparate times during the injury/repair time course.…”

Diffusion tensor imaging detects white matter abnormalities and associated cognitive deficits in chronic adolescent TBI

“…Evidence from combined histological and DTI studies utilizing animal models of acute and subacute brain insult suggest that DTI variables can identify the primary axotomy and secondary demyelination arising from TBI [13–17]. Acutely, decreased FA was related to decreased white matter fibre directional coherence and decreased AD was associated with axon degeneration [13, 14, 16, 17]. In the sub-acute phase of TBI, AD returned to pseudo-baseline but increased RD was associated with secondary demyelination [14, 16, 17].…”

“…Acutely, decreased FA was related to decreased white matter fibre directional coherence and decreased AD was associated with axon degeneration [13, 14, 16, 17]. In the sub-acute phase of TBI, AD returned to pseudo-baseline but increased RD was associated with secondary demyelination [14, 16, 17]. In the chronic phase of TBI, decreased FA and increased RD and MD have been consistently reported [18–21].…”

Diagnostic, Prognostic, and Advanced Imaging in Severe Traumatic Brain Injury

“…The aspect of FA measurements that is of particular relevance to sTBI is its ability to detect structural changes in the white matter axons that are susceptible to TAI. Low FA in the white matter has been correlated with histopathological evidence of TAI in experimental animal models [72,73]. In addition, low FA in white matter regions that are known to be susceptible to TAI (e.g., corpus callosum and internal capsules) is associated with a broad range of neurological deficits in patients with sTBI [74][75][76][77][78][79][80][81][82][83].…”