Assessing Spatial Relationships between Axonal Integrity, Regional Brain Volumes, and Neuropsychological Outcomes after Traumatic Axonal Injury

Abstract

Diffuse traumatic axonal injury (TAI) is a type of traumatic brain injury (TBI) characterized predominantly by white matter damage. While TAI is associated with cerebral atrophy, the relationship between gray matter volumes and TAI of afferent or efferent axonal pathways remains unknown. Moreover, it is unclear if deficits in cognition are associated with post-traumatic brain volumes in particular regions. The goal of this study was to determine the relationship between markers of TAI and volumes of cortical and subcortical structures, while also assessing the relationship between cognitive outcomes and regional brain volumes. High-resolution magnetic resonance imaging scans were performed in 24 patients with TAI within 1 week of injury and were repeated 8 months later. Diffusion tensor imaging (DTI) tractography was used to reconstruct prominent white matter tracts and calculate their fractional anisotropy (FA) and mean diffusivity (MD) values. Regional brain volumes were computed using semi-automated morphometric analysis. Pearson's correlation coefficients were used to assess associations between brain volumes, white matter integrity (i.e., FA and MD), and neuropsychological outcomes. Post-traumatic volumes of many gray matter structures were associated with chronic damage to related white matter tracts, and less strongly associated with measures of white matter integrity in the acute scans. For example, left and right hippocampal volumes correlated with FA in the fornix body (r ¼ 0.600, p ¼ 0.001; r ¼ 0.714, p < 0.001, respectively). In addition, regional brain volumes were associated with deficits in corresponding neuropsychological domains. Our results suggest that TAI may be a primary mechanism of post-traumatic atrophy, and provide support for regional morphometry as a biomarker for cognitive outcome after injury.

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

“…Significant differences in the FA, ADC, or MD, or other DTIderived diffusivity metrics have been demonstrated in studies of TBI in both adults (Bigler et al, 2010b;Kraus et al, 2007;Lipton et al, 2008;Perlbarg et al, 2009;Warner et al, 2010a) and children (Ewing-Cobbs et al, 2008;Levin et al, 2008;McCauley et al, 2011;Wilde et al, 2006bWilde et al, , 2010Wozniak et al, 2007;Wu et al, 2010a;Yuan et al, 2007), with decreases in FA and increases in measures of diffusivity often found in chronic post-injury intervals. More importantly, changes in DTIderived measures have shown correlation with injury severity (Arfanakis et al, 2002;Benson et al, 2007;Wilde et al, 2010;Yuan et al, 2007), functional outcome (Huisman et al, 2004;Levin et al, 2008;Salmond et al, 2006;Wozniak et al, 2007), neurologic functioning (Caeyenberghs et al, 2010a,b), and cognitive ability (Bigler et al, 2010b;Ewing-Cobbs et al, 2008;Kraus et al, 2007;Kumar et al, 2009;Levin et al, 2008;McCauley et al, 2011;Niogi et al, 2008;Salmond et al, 2006;Warner et al, 2010a;Wilde et al, 2010). Longitudinal studies have also indicated that DTI might serve as a tool for revealing changes in the neural tissue during recovery from TBI (Bendlin et al, 2008;Sidaros et al, 2008;Wu et al, 2010a).…”

“…Volumetric analysis allows for the detection or quantification of white and gray matter volumes, either globally or for specific regions, as well as cerebrospinal fluid and total intracranial volume, generally using threedimensional (3-D) volumetric high resolution T1-weighted imaging or combinations of complementary MR sequences. 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).…”

“…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).…”

Early Cortical Thickness Change after Mild Traumatic Brain Injury following Motor Vehicle Collision

“…34,[38][39][40] Structural analyses involved preprocessing high resolution T1-weighted MRI data (including motion correction, transformation to Talairach space, intensity normalization, skull stripping, segmentation, tessellation, smoothing of the cortical gray/white border, and inflating sulci to create a spherical model of each hemisphere).…”

Strategy‐based reasoning training modulates cortical thickness and resting‐state functional connectivity in adults with chronic traumatic brain injury

“…MRI‐based morphometry has revealed altered cortical thickness and volume within individuals who have sustained a TBI (Bendlin et al., 2008; Gale, Baxter, Roundy, & Johnson, 2005; Kim et al., 2008; Sidaros et al., 2009; Spitz et al., 2013; Tate et al., 2014; Turken et al., 2009; Warner et al., 2010; Zhou et al., 2013). These altered cortical morphometric properties are frequently associated with functional deficits (Gale et al., 2005; Palacios et al., 2013; Sidaros et al., 2009; Spitz et al., 2013; Warner et al., 2010; Zhou et al., 2013), and correspondences between MRI‐based and histological morphometric data of TBI individuals have been reported (Maxwell, MacKinnon, Stewart, & Graham, 2009). RsFC MRI measures the temporal coherency of blood oxygenation level‐dependent (BOLD) signal at rest and it allows us to identify how the brain's intrinsic functional networks are organized (see van Dijk et al., 2010 for review).…”