White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain, 130(Pt 10), 2508-2519

Wayne State University, Detroit, Michigan, United States
Brain (Impact Factor: 9.2). 11/2007; 130(Pt 10):2508-19. DOI: 10.1093/brain/awm216
Source: PubMed


Traumatic brain injury (TBI) is a serious public health problem. Even injuries classified as mild, the most common, can result in persistent neurobehavioural impairment. Diffuse axonal injury is a common finding after TBI, and is presumed to contribute to outcomes, but may not always be apparent using standard neuroimaging. Diffusion tensor imaging (DTI) is a more recent method of assessing axonal integrity in vivo. The primary objective of the current investigation was to characterize white matter integrity utilizing DTI across the spectrum of chronic TBI of all severities. A secondary objective was to examine the relationship between white matter integrity and cognition. Twenty mild, 17 moderate to severe TBI and 18 controls underwent DTI and neuropsychological testing. Fractional anisotropy, axial diffusivity and radial diffusivity were calculated from the DTI data. Fractional anisotropy was the primary measure of white matter integrity. Region of interest analysis included anterior and posterior corona radiata, cortico-spinal tracts, cingulum fibre bundles, external capsule, forceps minor and major, genu, body and splenium of the corpus callosum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and sagittal stratum. Cognitive domain scores were calculated from executive, attention and memory testing. Decreased fractional anisotropy was found in all 13 regions of interest for the moderate to severe TBI group, but only in the cortico-spinal tract, sagittal stratum and superior longitudinal fasciculus for the mild TBI group. White Matter Load (a measure of the total number of regions with reduced FA) was negatively correlated with all cognitive domains. Analysis of radial and axial diffusivity values suggested that all severities of TBI can result in a degree of axonal damage, while irreversible myelin damage was only apparent for moderate to severe TBI. The present data emphasize that white matter changes exist on a spectrum, including mild TBI. An index of global white matter neuropathology (White Matter Load) was related to cognitive function, such that greater white matter pathology predicted greater cognitive deficits. Mechanistically, mild TBI white matter changes may be primarily due to axonal damage as opposed to myelin damage. The more severe injuries impact both. DTI provides an objective means for determining the relationship of cognitive deficits to TBI, even in cases where the injury was sustained years prior to the evaluation.

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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:
    Brain 06/2015; 138(Pt 8). DOI:10.1093/brain/awv152 · 9.20 Impact Factor
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    • "To examine whether blast-related mTBI was characterized by spatially heterogeneous reductions in FA rather than reductions in FA in specific white matter tracts, we followed previously published procedures (Kraus et al., 2007; Mac Donald et al., 2011 "
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    ABSTRACT: Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF Veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI-LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.
    Clinical neuroimaging 04/2015; 28. DOI:10.1016/j.nicl.2015.04.001 · 2.53 Impact Factor
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    • "Consistent with the approach employed by Kraus et al. (2007), lesion load was calculated as the total number of grey and white matter brain regions that showed signal abnormality as seen on SWI. This measure was employed because it is thought to be sensitive to diffuse abnormalities given that it considers the actual number of affected areas across the brain independent of individual variability in the specific location of these abnormalities (Kraus et al., 2007). "
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    ABSTRACT: The purpose of this investigation was to evaluate the differential influence of age-at-insult and brain pathology on longitudinal outcome and recovery of pragmatic communication after paediatric TBI. Children and adolescents with TBI (n=106) were categorized according to timing of brain insult: (i) Middle Childhood (5-9 years; n = 41); (ii) Late Childhood (10-11 years; n = 39); and (iii) Adolescence (12-15 years; n = 32) and group-matched to a typically developing (TD) control group (n=43). Participants were assessed on pragmatic language and behavioural function at 6- and 24-months post-TBI. While adolescent TBI was associated with post-acute disruption to skills that preceded recovery to age-expected levels by 2-years post-injury, the middle childhood TBI group demonstrated impairments at 6-months post- injury that were maintained at 2-year follow up. Reduced pragmatic communication was associated with frontal, temporal and corpus callosum lesions, as well as more frequent externalizing behaviour symptoms at 24-months post injury.
    Brain and Language 02/2015; 142C. DOI:10.1016/j.bandl.2015.01.007 · 3.22 Impact Factor
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