Perspectives Commentary on: Neuroimaging Changes in the Brain in Contact versus Noncontact Sport Athletes Using Diffusion Tensor Imaging by Gajawelli et al. pp. 824-828.

Russell R. Lonser, M.D. Chair, The Ohio State University Wexner Medical Center Department of Neurological Surgery

Diffusion Tensor Imaging in the Spotlight on Concussion H. Francis Farhadi and Russell R. Lonser


ild traumatic brain injury (mTBI), including concussion, associated with contact sports and activities of daily living is increasingly recognized as a cause for disruption of cognitive functioning involving attention, executive functions, and memory. Emerging evidence indicates that traumatic axonal injury may be associated with long-term cognitive and neuropsychological disability in severe brain injury, as well as the common transient signs and symptoms linked to mTBI. Because traditional neuroimaging sequences are insensitive to the subtle white matter changes that may underlie axonopathy in mTBI, magnetic resonance (MR) diffusion tensor imaging (DTI) has been used for detection of fiber tract disruption and tracking white matter changes, as well as a potential prognostic marker of longterm clinical outcome.

DTI measures asymmetric or “anisotropic” diffusion of water along white matter tracts. MR DTI indirectly offers high-resolution insight into axonal microstructural integrity. Axial diffusivity (AD) refers to the direction of maximal diffusion, while the 2 remaining mutually perpendicular eigenvalues correspond to the radial diffusivity (RD). While AD is thought to primarily reflect axonal integrity, RD likely corresponds to myelin sheath function. The asymmetrical pattern of diffusion is described quantitatively as fractional anisotropy (FA), which is a ratio of all 3 eigenvalues and ranges from 0 (random, multidirectional movement) to 1.0 (movement in one particular direction). While mean diffusivity (MD) is a measure of average diffusivity, DTI “trace” is a measure of the magnitude of water diffusion and ranges from

Key words Diffusion tensor imaging - Magnetic resonance imaging - Traumatic brain injury -


Abbreviations and Acronyms AD: Axial diffusivity DTI: Diffusion tensor imaging FA: Fractional anisotropy MD: Mean diffusivity MR: Magnetic resonance mTBI: Mild traumatic brain injury RD: Radial diffusivity

0 (no movement) to 1.5 x 10 movement) in brain tissue.


mm2/second (totally unrestricted

Animal studies have confirmed that DTI parameters including AD and RD fluctuate early after brain injury (4). It has been hypothesized that the associated mechanical forces on axons and their supporting structures result in extracellular to intracellular shifts of water, which in turn lead to cytotoxic edema and changes in water content within the myelin sheath (1). As a result, even small fluid shifts can lead to decreased diffusivity perpendicular to the axon (decreased RD). In severe forms of human TBI, DTI measurements appear to at least partially predict clinical outcome (7). Nevertheless, for milder injuries (including contact sport-associated mTBIs), the underlying precise injury mechanism likely widely influences the relationship of these parameters to the actual evolving microstructural changes. Early and delayed DTI changes have been variably linked to mTBI patients when compared to healthy controls. Most studies have demonstrated a lower FA and/or higher MD in large white matter tracts including the centrum semiovale, internal capsule, as well as the splenium and genu of the corpus callosum. Alternatively, other studies have revealed higher FA and lower RD values in the corpus callosum that were linked to timing of imaging after mTBI ranging from days to weeks. Recently, Mayer et al. performed a prospective study in 22 patients with mTBI that revealed increased FA and lower RD, at an average of 12 days after injury, within the genu and several hemispheric white matter tracts

Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA To whom correspondence should be addressed: H. Francis Farhadi, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2013) 80, 6:794-795.



including the corona radiata, uncinate fasciculus, internal capsule, and splenium (5).

matter tract changes may be small. Identification of the most sensitive or valid DTI parameter for mTBI remains elusive to date.

Serial DTI assessments could potentially provide an objective measure of concussive injury, which could guide clinical decision making, including return-to-play (or work) considerations; however, findings to date have been inconsistent with respect to the vector of FA and MD changes temporally post-mTBI. Studies specifically combining continuous on-field (including during practice) monitoring of head impacts along with serial DTI assessments hold promise in elucidating the connection between repetitive white matter “strain” and eventual microstructural white matter changes, as indicated by FA and MD measurements. McAllister et al. found that mean and maximum strain rate (as measured by the Head Impact Telemetry System) correlated with FA changes, while MD correlated with injury-to-imaging interval (6). Validation of head kinematic technology combined with longitudinal measurement of DTI parameters could potentially determine the influence of repetitive mTBIs and/or so-called repetitive “subconcussive” blows.

Gajawelli et al. should be lauded for advancing our understanding of the potential applicability of serial DTI analysis in the evaluation of contact sport-associated mTBI. Rather than a region-ofinterest analysis, they present a voxel-based approach that identifies significant FA changes in a number of white matter tracts ranging from the inferior fronto-occipital fasciculus to portions of the corona radiata and corpus callosum. As with other studies in this area, conclusions are complicated by small sample and an inability to directly correlate the imaging findings to the athlete’s specific recent and remote mTBI history. In the future, corroborative neuropsychological testing and follow-up imaging in the “noncontact” athlete cohort would be useful to further validate the specificity of the findings. This is particularly true as the DTI acquisition protocol used in this study was limited to one form of analysis including for the spatial smoothing required of voxel-based morphometric approaches.

There have been several attempts to correlate DTI changes to postconcussion signs/symptoms. Specifically, Bazarian et al. found significantly lower mean trace in the left anterior internal capsule and higher FA in the posterior corpus callosum in a small subset of patients who suffered from persistent postconcussive symptoms (1, 3). Nevertheless, other reports have failed to detect consistent DTI findings in mTBI patients complaining of persistent postconcussive symptoms (2, 8). Taken together, these different findings highlight the difficulty of studying a highly heterogeneous diagnosis of mTBI where the magnitude of white

REFERENCES 1. Bazarian JJ, Zhong J, Blyth B, Zhu T, Kavcic V, Peterson D: Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. J Neurotrauma 24: 1447-1459, 2007. 2. Lange RT, Iverson GL, Brubacher JR, Mädler B, Heran MK: Diffusion tensor imaging findings are not strongly associated with postconcussional disorder 2 months following mild traumatic brain injury. J Head Trauma Rehabil 27:188-198, 2012. 3. Lipton ML, Gellella E, Lo C, Gold T, Ardekani BA, Shifteh K, Bello JA, Branch CA: Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability: a voxelwise analysis of diffusion tensor imaging. J Neurotrauma 25:1335-1342, 2008.

Despite early indications that microstructural damage to the brain can be inferred using DTI, this imaging sequence cannot currently predict postconcussion symptoms or clinical outcome in individual subjects. Cautious interpretation is warranted until large-scale prospective studies with longitudinal evaluation of validated DTI parameters in athletes (and other concussed individuals) are undertaken to ultimately address this modality’s potential clinical utility in tracking progression and prognosticating outcome. Nevertheless, the results to date, including the current study, are encouraging and suggest that the severity of mTBI will eventually be better assessed using DTI.

4. Mac Donald CL, Dikranian K, Bayly P, Holtzman D, Brody D: Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci 27: 11869-11876, 2007. 5. Mayer AR, Ling J, Mannell MV, Gasparovic C, Phillips JP, Doezema D, Reichard R, Yeo RA: A prospective diffusion tensor imaging study in mild traumatic brain injury. Neurology 74:643-650, 2010. 6. McAllister TW, Ford JC, Ji S, Beckwith JG, Flashman LA, Paulsen K, Greenwald RM: Maximum principal strain and strain rate associated with concussion diagnosis correlates with changes in corpus callosum white matter indices. Ann Biomed Eng 40:127-140, 2012. 7. Sidaros A, Engberg AW, Sidaros K, Liptrot MG, Herning M, Petersen P, Paulson OB, Jernigan TL, Rostrup E: Diffusion tensor imaging during


recovery from severe traumatic brain injury and relation to clinical outcome: a longitudinal study. Brain 131(Pt 2):559-572, 2008. 8. Zhang K, Johnson B, Pennell D, Ray W, Sebastianelli W, Slobounov S: Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study. Exp Brain Res 204:57-70, 2010.

Citation: World Neurosurg. (2013) 80, 6:794-795. Journal homepage: Available online: 1878-8750/$ - see front matter ª 2013 Elsevier Inc. All rights reserved.


Diffusion tensor imaging in the spotlight on concussion.

Diffusion tensor imaging in the spotlight on concussion. - PDF Download Free
431KB Sizes 0 Downloads 0 Views