The young brain and concussion: imaging as a biomarker for diagnosis and prognosis

Abstract

Concussion (mild traumatic brain injury (mTBI)) is a significant pediatric public health concern. Despite increased awareness, a comprehensive understanding of the acute and chronic effects of concussion on central nervous system structure and function remains incomplete. Here we review the definition, epidemiology, and sequelae of concussion within the developing brain, during childhood and adolescence, with current data derived from studies of pathophysiology and neuroimaging. These findings may contribute to a better understanding of the neurological consequences of traumatic brain injuries, which in turn, may lead to the development of brain biomarkers to improve identification, management and prognosis of pediatric patients suffering from concussion.

Figure 1

Post-concussive signs and symptoms. Physical, cognitive, emotional and sleep signs and symptoms potentially present after sustaining a concussion.

Figure 2

Temporal Consequences of Concussion. The figure shows the current understanding of the implications of mTBI and its chronologic burden.

Figure 3

Metabolic and Anatomical Changes. A: Neuronal Changes. Schematic depiction of the process that lead to neuronal cell injury after a concussion(Adapted from (Giza and Hovda, 2001)). B: Axonal Changes. Postmortem APP immunohistochemistry of the corpus callosum after TBI showing axonal bulb formation, and points of interruption (a–d). From (Johnson et al., 2012b); permission pending.

Figure 4

Brain-Related Behavioral Changes. Conceptualized regional brain involvement and the potential consequences of concussion.

Figure 5

Acute and chronic consequences of different grades of severity of Concussion. Notice that even though mTBI seems to recover quickly, it continues to present cognitive problems along time (from http://www.publichealth.va.gov/docs/vhi/traumatic-brain-injury-vhi.pdf; permission pending).

Figure 6

Temporal changes following Concussion. Onset and persistency of post-concussive headache due to different mechanisms involving anatomical and blood flow changes.

Figure 7

Functional Imaging - fMRI (Evoked Measures): Functional MRI image showing brain activation during a verbal working memory task in healthy controls, mTBI patients with low post concussive symptoms (PCS) and moderate PCS. The image shows additional activation in the posterior brain regions, and less activation in the frontal regions, when patients had low and moderate post concussive symptoms (PCS), compared to control subjects. These changes depict poorer brain activation in frontal areas in patients with PCS while performing neurocognitive testing. (From (Chen et al., 2007); permission pending).

Figure 8

A: Functional Imaging - fMRI (Resting State). Functional MRI comparing healthy controls with patients with traumatic brain injury: Patients showed increased posterior cingulate cortex and precuneus functional connectivity activation than controls. The results hypothesize that such variations are a direct reflection of brain injury and also a representation of adaptive response to cognitive impairment. (From (Sharp et al., 2011); permission pending). B: Functional connectivity. Functional MRI showing comparing resting state networks of normal volunteer vs. mTBI patients. The figure indicates the differences between shared (red) and non-shared (yellow) connections from left and right parietal lobes. (From (Johnson et al., 2012a); permission pending).

Figure 9

Magnetic Resonance Spectroscopy. MRS image comparing the right and left parieto occipital regions, (a and b, c and d respectively) between a mTBI patient and a healthy control: N-acetyl aspartate (NAA) and total choline (Cho) are significantly altered in b1 compared to the control subject at c1 and d1. (From (Govind et al., 2010); permission pending).

Figure 10

Morphometric Imaging in Concussion. Top. DTI fiber tractography showing track fiber pattern to the left DLPFC in healthy controls and mTBI patients: 15 student-athletes (mean age 20.8 ± 1.7 years) who suffered from sport-related mTBI (collegiate rugby, ice hockey and soccer players). Statistical analysis demonstrated that these different patterns involved significant variations in diffusivity between these two groups; the mTBI group had decreased diffusivity. (From (Zhang et al., 2010a); permission pending). Bottom. DTI fiber tractography detail of a mTBI patient at the level of the right semiovale center: Mild TBI patients possessed a GCS of 13–15 after a traffic accident, blow to the head or fall. Note the discontinuous characteristics of the fibers, hypothesized to be caused by trauma. (From (Rutgers et al., 2008); permission pending).

Figure 11

Imaging uses. The figure shows the broad range of current potential uses of imaging in this field, with physiological, diagnostic and therapeutic implications.

Figure 12

Brain alterations shown on functional imaging without behavioral changes. fMRI image of highschool football players without clinically diagnosed concussion, performing neurocognitive testing before football season and during football season: Even in the absence of concussion [in 8 out of 21 athletes], fMRI shows significantly different changes in the athletes brain, such changes are correlated with a poorer performance in neurocognitive testing. (From (Talavage et al., 2010); permission pending).

Figure 13

Chart depicting how a new approach for concussion can be reached with imaging and how it can change the field. Imaging encloses different and specific aspects of this pathology, which makes it a precise and sensitive tool in TBI diagnosis, pathophysiology and treatment.