Neuroimaging of the Injured Pediatric Brain: Methods and New Lessons

Abstract

Traumatic brain injury (TBI) is a significant public health problem in the United States, especially for children and adolescents. Current epidemiological data estimate over 600,000 patients younger than 20 years are treated for TBI in emergency rooms annually. While many patients experience a full recovery, for others there can be long-lasting cognitive, neurological, psychological, and behavioral disruptions. TBI in youth can disrupt ongoing brain development and create added family stress during a formative period. The neuroimaging methods used to assess brain injury improve each year, providing researchers a more detailed characterization of the injury and recovery process. In this review, we cover current imaging methods used to quantify brain disruption post-injury, including structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, resting state fMRI, and magnetic resonance spectroscopy (MRS), with brief coverage of other methods, including electroencephalography (EEG), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). We include studies focusing on pediatric moderate-severe TBI from 2 months post-injury and beyond. While the morbidity of pediatric TBI is considerable, continuing advances in imaging methods have the potential to identify new treatment targets that can lead to significant improvements in outcome.

Keywords: DTI; MRI; MRS; brain imaging; cognitive; fMRI; longitudinal; multimodal; pediatric; traumatic brain injury.

Figure 1

Between-group longitudinal changes in cortical thickness. Blue regions indicate relative cortical thinning, and red-orange regions indicate relative cortical increase in the traumatic brain injury (TBI) group over the 3- to 18-month post-injury time interval. Reprinted with permission from Wilde and others (2012b).

Figure 2

Longitudinal changes in along-tract mean diffusivity in TBI-slow-IHTT, TBI-normal-IHTT, and healthy controls. The group-averaged maps are shown for both time points, across TBI-slow-IHTT (N = 11), TBI-normal-IHTT (N = 10), and healthy controls (N = 20). Approximately 12 months passed between the beginning and ending time point. As indicated in the legend, blue areas have the lowest mean diffusivity (MD) and therefore highest WM organization, while red areas have the highest MD. The healthy controls show minimal decreases in MD. The TBI-slow-IHTT group shows widespread increases in MD. The TBI-normal-IHTT group shows a mixture. TBI = traumatic brain injury; IHTT = interhemispheric transfer time; WM = white matter. Reprinted with permission from Dennis and others (2017).

Figure 3

Significant differences between groups in resting state functional magnetic resonance imaging (rsfMRI). Relative to the typically developing (TD) group, the traumatic brain injury (TBI) group demonstrated lower functional connectivity between the rostral anterior cingulate cortex (rACC) seed and temporal pole (a) and dorsal medial prefrontal cortex (MPFC) (b), and between the right amygdala seed and rostral and ventral MPFC (c). Activation is overlaid onto an individual subject’s brain transformed into Talairach space. Left side of brain is on left side of the figure. Reprinted with permission from Newsome and others (2013).

Figure 4

Between-group comparison (typically developing [TD] > traumatic brain injury [TBI]) of inhibition-related activation. Positive activation regions are where TD controls demonstrated greater activation than TBI (TD > TBI). Images are from z = +32 to z = +76, with the following parameters: p-threshold = 0.001 uncorrected, cluster size threshold = 50. Reprinted with permission from Tlustos and others (2015).

Figure 5

Total mean metabolite ratios plotted by neurologic outcomes or control (CNTL). Ratios were calculated from all voxels including those containing hemorrhagic and nonhemorrhagic diffuse axonal injury (DAI) lesions for patients with traumatic brain injury (TBI). Asterisk indicates P = 0.01; double asterisk, P = 0.000. Reprinted with permission from Holshouser and others (2005).

Figure 6

Summary of group differences in structural and metabolic data. Results from structural MRI, diffusion MRI, and magnetic resonance spectroscopy (MRS) are summarized in this figure. WM = white matter organization; vol = volume; CT = cortical thickness; NAA = N-acetylaspartate; Cho = choline. Results are summarized by brain lobe. T1 = post-acute (2–6 months post-injury), T2 = chronic (6 months to 2 years post-injury), T3 = long term (>2 years post-injury). Downward arrows indicate areas/measures that were lower in traumatic brain injury (TBI) versus typically developing (TD). Angled arrows indicate differences in longitudinal changes between time-points—upward angled arrows indicate greater increases in TBI versus TD over time, downward angled arrows indicate greater decreases in TBI versus TD over time, straight arrows indicate no change. Dash (–) indicates no significant result to report. Mixed changes are reported for some areas, indicating that either studies are conflicting, or that subgroups within the TBI group show opposite effects.