Salmond, C. H. et al. Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices. Neuroimage 29, 117-124

Wolfson Brain Imaging Centre, Box 65, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, UK.
NeuroImage (Impact Factor: 6.36). 02/2006; 29(1):117-24. DOI: 10.1016/j.neuroimage.2005.07.012
Source: PubMed


Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

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    • "No adverse events related to the scans were observed. Patients with TBI who had been included in a previous microdialysis study (Magnoni et al., 2012) were re-approached for evaluation with an identical imaging protocol in the chronic phase, based on the consideration that fractional anisotropy abnormalities (reductions) can be observed long after injury (Inglese et al., 2005; Nakayama et al., 2006; Salmond et al., 2006; Kraus et al., 2007; Niogi et al., 2008; Sidaros et al., 2008; Kinnunen et al., 2011), likely resulting from a persistent fractional anisotropy depression (Sidaros et al., 2008; Mac Donald et al., 2011). Patients were excluded if they had contraindications to MRI, ventricular shunts, or any other metallic implants. "
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    ABSTRACT: Axonal injury is a major contributor to adverse outcomes following brain trauma. However, the extent of axonal injury cannot currently be assessed reliably in living humans. Here, we used two experimental methods with distinct noise sources and limitations in the same cohort of 15 patients with severe traumatic brain injury to assess axonal injury. One hundred kilodalton cut-off microdialysis catheters were implanted at a median time of 17 h (13-29 h) after injury in normal appearing (on computed tomography scan) frontal white matter in all patients, and samples were collected for at least 72 h. Multiple analytes, such as the metabolic markers glucose, lactate, pyruvate, glutamate and tau and amyloid-β proteins, were measured every 1-2 h in the microdialysis samples. Diffusion tensor magnetic resonance imaging scans at 3 T were performed 2-9 weeks after injury in 11 patients. Stability of diffusion tensor imaging findings was verified by repeat scans 1-3 years later in seven patients. An additional four patients were scanned only at 1-3 years after injury. Imaging abnormalities were assessed based on comparisons with five healthy control subjects for each patient, matched by age and sex (32 controls in total). No safety concerns arose during either microdialysis or scanning. We found that acute microdialysis measurements of the axonal cytoskeletal protein tau in the brain extracellular space correlated well with diffusion tensor magnetic resonance imaging-based measurements of reduced brain white matter integrity in the 1-cm radius white matter-masked region near the microdialysis catheter insertion sites. Specifically, we found a significant inverse correlation between microdialysis measured levels of tau 13-36 h after injury and anisotropy reductions in comparison with healthy controls (Spearman's r = -0.64, P = 0.006). Anisotropy reductions near microdialysis catheter insertion sites were highly correlated with reductions in multiple additional white matter regions. We interpret this result to mean that both microdialysis and diffusion tensor magnetic resonance imaging accurately reflect the same pathophysiological process: traumatic axonal injury. This cross-validation increases confidence in both methods for the clinical assessment of axonal injury. However, neither microdialysis nor diffusion tensor magnetic resonance imaging have been validated versus post-mortem histology in humans. Furthermore, future work will be required to determine the prognostic significance of these assessments of traumatic axonal injury when combined with other clinical and radiological measures. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
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    • "In human cases of chronic TBI, reduced fractional anisotropy with increased mean diffusivity are consistently reported (Inglese et al., 2005; Salmond et al., 2006; Benson et al., 2007; Kraus et al., 2007; Xu et al., 2007; Niogi et al., 2008; Sidaros et al., 2008; Kennedy et al., 2009; Kinnunen et al., 2011; Mac Donald et al., 2011). Across the TBI spectrum, whole brain voxel-wise techniques such as TBSS typically reveal a diffuse pattern of anomalies affecting various major fibre tracts. "
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    ABSTRACT: Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.
    Full-text · Article · Sep 2014 · Brain
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    • "The decrease in FA and axial diffusivity along the right superior longitudinal fasciculus in subjects with MD post- TBI relative to TBI patients who did not develop MD, as well as in those with MD (no TBI) compared with matched controls (with no history of MD or TBI) is consistent with the literature. For example, the low FA regions reported in a DTI study of post-TBI patients [Salmond et al., 2006] are very similar to those found in a study of patients with first-episode treatment-naı¨ve MD [Ma et al., 2007] and from a group of patients with first-episode remitted depression [Yuan et al., 2007], which include the right parietal lobe and right frontal gyri. Furthermore, Alexopoulos et al. [2008] found similar regions to have "
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    ABSTRACT: Background: Many people with a traumatic brain injury (TBI), even mild to moderate, will develop major depression (MD). Recent studies of patients with MD suggest reduced fractional anisotropy (FA) in dorsolateral prefrontal cortex (DLPFC), temporal lobe tracts, midline, and capsule regions. Some of these pathways have also been found to have reduced FA in patients with TBI. It is unknown whether the pathways implicated in MD after TBI are similar to those with MD without TBI. This study sought to investigate whether there were specific pathways unique to TBI patients who develop MD. Methods: A sample of TBI-MD subjects (N = 14), TBI-no-MD subjects (N = 12), MD-no-TBI (N = 26), and control subjects (no TBI or MD, N = 23), using a strict measurement protocol underwent psychiatric assessments and diffusion tensor brain Magnetic Resonance Imaging (MRI). Results: The findings of this study indicate that (1) TBI patients who develop MD have reduced axial diffusivity in DLPFC, corpus callosum (CC), and nucleus accumbens white matter tracts compared to TBI patients who do not develop MD and (2) MD patients without a history of TBI have reduced FA along the CC. We also found that more severe MD relates to altered radial diffusivity. Conclusions: These findings suggest that compromise to specific white matter pathways, including both axonal and myelination aspects, after a mild TBI underlie the susceptibility of these patients developing MD.
    Full-text · Article · Jan 2014 · Human Brain Mapping
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