Neuroimaging in repetitive brain trauma

Abstract

Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.

Figure 1

Results of the Tract-based spatial statistics analysis and diffusivity measures for individual swimmers and soccer players. Top: the diffusion tensor for each voxel was estimated by the multivariate linear fitting algorithm, and the tensor matrix was diagonalized to obtain three pairs of eigenvalues and eigenvectors. Voxelwise summary parameters included radial diffusivity and axial diffusivity. Group analyses were performed using whole-brain threshold-free cluster enhancement to obtain significant differences between groups at P < 0.05. After accounting for multiple comparisons using the family-wise error rate, the voxels highlighted in red demonstrate significantly increased radial diffusivity (A) and axial diffusivity (B) values for the soccer group compared with swimmers. Bottom: voxels with a significant group difference as revealed by Tract-based spatial statistics (top) were merged to a single cluster. Circles indicate individual values, squares indicate mean values, and error bars indicate 95% confidence intervals. Diffusivity measures were obtained for each individual and plotted for the two study groups. Linear regression showed no significant association of age or years of training with (A) radial diffusivity (P = 0.13 and P = 0.12, respectively) or (B) for axial diffusivity values (P = 0.22 and P = 0.54, respectively). Used with permission from [30].

Figure 2

L-COSY spectra from healthy control (left) and athlete with a history of repetitive brain trauma (RBT; right). Spectroscopy was performed at 3T using a 32 channel head coil and voxel size of 3 × 3 × 3 cm³ in the posterior cingulated gyrus; increment size 0.8 ms; 64 increments with 8 averages resulting in an acquisition time of 12.8 minutes; acquired vector 1,024 points; acquisition time 512 ms; spectral width in F2 2,000 Hz and spectral width in F1 1,250 Hz. For presentation the spectra were calibrated to the lysine cross peak at 3.00 to 1.67 ppm. Asp, aspartate; Cho, choline; Cr, creatine; Fuc, fucose; GABA, gamma-aminobutyric acid; Glx, glutamate/glutamine; Lys, lysine; m1, macromolecule; mI, myo-insitol; NAA, N-acetyl aspartate; Thr, threonine.

Figure 3

T807 tau tracer. Sagittal images from 80 to 100 minutes post-injection of a 56-year-old healthy subject (top left), mild cognitively impaired (MCI) subject (top right), mild Alzheimer’s disease (AD) subject with mini-mental state exam (MMSE) 21 (bottom left), and severe AD subject with MMSE 7 (bottom right). The intensity and extension of T807 uptake correlated to Braak and Braak stages of phosphorylated tau deposition, except in the area where severe neuronal degeneration is expected, for which the mild AD subject had the highest cortical retention. Reprinted from the Journal of Alzheimer's Disease, volume 34 (No 2) by Chien et al. Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807, p465, Copyright 2013, with permission from IOS Press [111].