Cerebral Atrophy after Traumatic White Matter Injury: Correlation with Acute Neuroimaging and Outcome

Abstract

Traumatic brain injury (TBI) is a pathologically heterogeneous disease, including injury to both neuronal cell bodies and axonal processes. Global atrophy of both gray and white matter is common after TBI. This study was designed to determine the relationship between neuroimaging markers of acute diffuse axonal injury (DAI) and cerebral atrophy months later. We performed high-resolution magnetic resonance imaging (MRI) at 3 Tesla (T) in 20 patients who suffered non-penetrating TBI, during the acute (within 1 month after the injury) and chronic stage (at least 6 months after the injury). Volume of abnormal fluid-attenuated inversion-recovery (FLAIR) signal seen in white matter in both acute and follow-up scans was quantified. White and gray matter volumes were also quantified. Functional outcome was measured using the Functional Status Examination (FSE) at the time of the chronic scan. Change in brain volumes, including whole brain volume (WBV), white matter volume (WMV), and gray matter volume (GMV), correlates significantly with acute DAI volume (r ¼ À0.69, À0.59, À0.58, respectively; p < 0.01 for all). Volume of acute FLAIR hyperintensities correlates with volume of decreased FLAIR signal in the follow-up scans (r ¼ À0.86, p < 0.001). FSE performance correlates with acute hyperintensity volume and chronic cerebral atrophy (r ¼ 0.53, p ¼ 0.02; r ¼ À 0.45, p ¼ 0.03, respectively). Acute axonal lesions measured by FLAIR imaging are strongly predictive of post-traumatic cerebral atrophy. Our findings suggest that axonal pathology measured as white matter lesions following TBI can be identified using MRI, and may be a useful measure for DAI-directed therapies.

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

“…Volumetric analysis using specific regions has demonstrated significant decreases in volume in both adult (Tomaiuolo et al, 2004;Warner et al, 2010a;Wilde et al, 2004Wilde et al, , 2006a and pediatric (Beauchamp et al, 2010;Fearing et al, 2008;Spanos et al, 2007;Wilde et al, 2005Wilde et al, , 2006bWilde et al, , 2007Wu et al, 2010a) subjects with TBI in the chronic post-injury interval. Additionally, voxel-based, whole-surface based, and tensorbased analyses have also demonstrated significant global reductions in cortical thickness (Merkley et al, 2008) and cortical gray matter volume Ding et al, 2008;Gale et al, 2005;Warner et al, 2010a,b) as well as white matter volume (Ding et al, 2008;Sidaros et al, 2009;Vannorsdall et al, 2010). Late volumetric measures have demonstrated relation to measures of clinical severity Schonberger et al, 2009;Trivedi et al, 2007), outcome, (Ding et al, 2008;Gale and Prigatano, 2010;Warner et al, 2010b), cognition (Bergeson et al, 2004;Fujiwara et al, 2008;Himanen et al, 2005;Serra-Grabulosa et al, 2005;Tomaiuolo et al, 2004;Warner et al, 2010a), and potential for benefit from rehabilitation intervention (Strangman et al, 2010), although other studies have reported no correlation between volumetric measures and functional outcome (Anderson et al, 1995;Sherer et al, 2006;Yount et al, 2002).…”

Transplantation of Marrow Stromal Cells Restores Cerebral Blood Flow and Reduces Cerebral Atrophy in Rats with Traumatic Brain Injury: In vivo MRI Study

“…Extensive axonal degeneration (Bigler, 1987;Ding et al, 2008;Mamere et al, 2009) and generalized cerebral atrophy (MacKenzie et al, 2002;Sidaros et al, 2009;Trivedi et al, 2007) associated with poor functional outcomes are the common sequelae. TBI-induced hypoperfusion, which could occur beyond the site of primary injury (Bonne et al, 2003;Hofman et al, 2001;Pasco et al, 2007), aggravates this trauma-triggered brain damage.…”

“…To date, however, the management of patients with TBI has generally concentrated on the prevention or amelioration of such devastating secondary Although mechanisms responsible for the observed therapeutic potential of MSCs remain to be explored, it is suggested that the beneficial effects are owed to the ability of MSCs to secrete an array of cytokines and trophic factors that activate endogenous restorative and regenerative processes, e.g., angiogenesis, synaptogenesis, gliogenesis, and neurogenesis (Chopp and Li, 2006;Mahmood et al, 2004aMahmood et al, , 2004b. Treatment of TBI with transplantation of MSCs may also moderate post-TBI hypoperfusion that results from impaired vasculature or disturbed hemodynamics (Hofman et al, 2001) and may reduce cerebral atrophy that occurs concomitantly with progressive neuronal loss (Immonen et al, 2009a;Smith et al, 1997) and diffuse axonal injury (Bigler, 1987;Ding et al, 2008;Mamere et al, 2009;Sidaros et al, 2009). To our knowledge, however, little is known about the dynamic effect of grafted MSCs on post-TBI hemodynamic and atrophic progression.…”

Brain volumetric correlates of inhibition and cognitive flexibility 16 years following childhood traumatic brain injury

“…Multiple studies have reported disruptions in these neural processes following diffuse axonal injury (DAI), which results from shearing of white matter-connecting pathways within neural networks associated with cognitive flexibility and inhibition Berryhill et al, 1995;Kinnunen et al, 2010;Levin et al, 2004;Ryan et al, 2014;Tasker, 2006). Perhaps not surprisingly, these childhood injuries are associated with widespread morphological changes, including reductions in cortical gray and white matter, as well as overall reductions in brain volume (Beauchamp, & Ditchfield, et al, 2011;Benson et al, 2007;Bigler, 2001Bigler, , 2007Ding et al, 2008;Gale, Baxter, Roundy, & Johnson, 2005;Trivedi et al, 2007;Wilde et al, 2005).…”