Diffusion tensor MR imaging in diffuse axonal injury. AJNR Am J Neuroradiol

Department of Medical Physics, University of Wisconsin, Madison 53706-1532, USA.
American Journal of Neuroradiology (Impact Factor: 3.59). 06/2002; 23(5):794-802.
Source: PubMed


Disruption of the cytoskeletal network and axonal membranes characterizes diffuse axonal injury (DAI) in the first few hours after traumatic brain injury. Histologic abnormalities seen in DAI hypothetically decrease the diffusion along axons and increase the diffusion in directions perpendicular to them. DAI therefore is hypothetically associated in the short term with decreased diffusion anisotropy. We tested this hypothesis by measuring the diffusion characteristics of traumatized brain tissue with use of diffusion tensor MR imaging.
Five patients with mild traumatic brain injuries and 10 control subjects were studied with CT, conventional MR imaging, and diffusion tensor imaging. All patients were examined within 24 hours of injury. In each participant, diffusion tensor indices from homologous normal-appearing white matter regions of both hemispheres were compared. These indices were also compared between homologous regions of each patient and the control group. In two patients, diffusion tensor images from the immediate post-trauma period were compared with those at 1 month follow-up.
Patients displayed significant reduction of diffusion anisotropy in several regions compared with the homologous ones in the contralateral hemisphere. Such differences were not observed in the control subjects. Significant reduction of diffusion anisotropy was also detected when diffusion tensor results from the patients were compared with those of the controls. This reduction was often less evident 1 month after injury.
White matter regions with reduced anisotropy are detected in the first 24 hours after traumatic brain injury. Therefore, diffusion tensor imaging may be a powerful technique for in vivo detection of DAI.

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Available from: Victor M Haughton, Oct 04, 2015
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    • "We therefore decided to use diffusion tensor magnetic resonance imaging (DTI) as an independent non-invasive method to assess axonal pathology in human TBI patients. DTI is a sensitive and robust method to assess white matter structural integrity following TBI (Arfanakis et al., 2002; Inglese et al., 2005; Nakayama et al., 2006; Salmond et al., 2006; Kraus et al., 2007; Newcombe et al., 2007; Niogi et al., 2008; Sidaros et al., 2008; Perlbarg et al., 2009; Niogi and Mukherjee, 2010; Kinnunen et al., 2011; Galanaud et al., 2012; Hulkower et al., 2013). DTI measures the directional diffusion of water, which in normal white matter is restricted by the orientation of axon bundles. "
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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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    • "Another study (Fernández-Espejo et al., 2012) used probabilistic tractography on patients with different DOC states (VS, MCS, exit-MCS) and controls to explain differences in the structural connectivity of the default mode network that correlate with clinical diagnosis and CRS-R. The prospective setup is rarely performed on such patients (Arfanakis et al., 2002; Dinkel et al., 2014). A follow-up study of up to 5 years post-injury, has recently been published regarding 13 severe TBI patients (Dinkel et al., 2014). "
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    ABSTRACT: BACKGROUND: Progress in neuroimaging has yielded new powerful tools which, potentially, can be applied to clinical populations, improve the diagnosis of neurological disorders and predict outcome. At present, the diagnosis of consciousness disorders is limited to subjective assessment and objective measurements of behavior, with an emerging role for neuroimaging techniques. In this review we focus on white matter alterations measured using Diffusion Tensor Imaging on patients with consciousness disorders, examining the most common diffusion imaging acquisition protocols and considering the main issues related to diffusion imaging analyses. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps and the potential role of neuroimaging in understanding the pathogenesis and clinical features of disorders of consciousness.
    Frontiers in Human Neuroscience 01/2015; 8. DOI:10.3389/fnhum.2014.01028 · 2.99 Impact Factor
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    • "The underlying mechanisms of these symptoms warrants further investigation and has significant clinical implications (Budde et al., 2011). Accurate diagnosis of mTBI is challenging because immunohistochemical techniques are invasive (Li et al., 2011) and standard MRI or CT may be insufficient (Arfanakis et al., 2002; Huisman et al., 2004). Conversely, diffusion tensor imaging (DTI) provides enhanced visualization of tissue microstructure (Sundgren et al., Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: We induced mild blunt and blast injuries in rats using a custom-built device and utilized in-house diffusion tensor imaging (DTI) software to reconstruct 3-D fiber tracts in brains before and after injury (1, 4, and 7 days). DTI measures such as fiber count, fiber length, and fractional anisotropy (FA) were selected to characterize axonal integrity. In-house image analysis software also showed changes in parameters including the area fraction (AF) and nearest neighbor distance (NND), which corresponded to variations in the microstructure of Hematoxylin and Eosin (H&E) brain sections. Both blunt and blast injuries produced lower fiber counts, but neither injury case significantly changed the fiber length. Compared to controls, blunt injury produced a lower FA, which may correspond to an early onset of diffuse axonal injury (DAI). However, blast injury generated a higher FA compared to controls. This increase in FA has been linked previously to various phenomena including edema, neuroplasticity, and even recovery. Subsequent image analysis revealed that both blunt and blast injuries produced a significantly higher AF and significantly lower NND, which correlated to voids formed by the reduced fluid retention within injured axons. In conclusion, DTI can detect subtle pathophysiological changes in axonal fiber structure after mild blunt and blast trauma. Our injury model and DTI method provide a practical basis for studying mild traumatic brain injury (mTBI) in a controllable manner and for tracking injury progression. Knowledge gained from our approach could lead to enhanced mTBI diagnoses, biofidelic constitutive brain models, and specialized pharmaceutical treatments.
    Journal of Biomechanics 11/2014; 47(15):3704-3711. DOI:10.1016/j.jbiomech.2014.09.026 · 2.75 Impact Factor
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