There is paucity in data regarding conventional imaging in patient with PPCS. A 2009 study by Schrader et al. compared MRI imaging in twenty young adults that sustained a concussion with brief (< 5 min) loss of consciousness to young adults with minor orthopedic injuries and showed no difference in MRI findings at 24 hours and 3 months (8). A 2011 critical review by Pulsipher et al. concluded that CT and MRI scans are classically low yield when examining concussions related to sport (1). Three studies were mentioned in this review, including two in boxing athletes and one in soccer athletes (5-7). A 2015 study examined whether or not imaging was cost effective for post-concussion symptoms (symptoms >2 weeks used as criteria in this study) and found two total relevant abnormal findings in 32 studies in 23 patients that included MRIs, CT scans and x-rays (9). There were five incidental findings reported, which included 3 with arachnoid cysts. The two relevant findings were a nondisplaced parietal skull fracture on a CT scan and multiple focal punctate foci in bilateral frontal, temporal, and parietal regions on an MRI scan. This study was done in a university setting and cost a total of more than $129,000 for these two findings (9).
Conventional studies of x-rays, CTs and MRIs are not sensitive in detecting diffuse axonal injury, which has been shown to be commonly associated with mild TBIs (10). Additionally, CTs and MRIs have been not been shown to correlate with clinical symptoms (10-11). Due to this, there has been a shift over the past decade investigating advanced imaging such as diffusion tensor imaging, MR-SPECT and functional MRI (fMRI).
A 2012 meta-analysis of 13 studies by Aoki et al. concluded that patients with mild TBI demonstrated a significant FA reduction in the corpus callosum without bias and provided strong evidence that DTI can detect microstructural damage in the white matter for mTBI patients. A 2013 study with 30 military veterans with chronic mild TBI showed significant loss of white matter integrity in primary fibers in a widely distributed pattern in major and smaller peripheral tracts when compared to non-TBI participants (16). This widespread pattern was typically associated with moderate and severe TBIs. Changes were also not evident on standard T1 weighted MRI images and there was more significant white loss matter correlated with feeling “dazed and confused,” but not with co-morbid conditions such as depression and PTSD (16). However, there has been some conflicting results in which areas of the brain are most affected and to what extent, but most studies do show white matter changes and decreased FA in areas of the corpus callosum (17). Another recent study has linked decreased FA in areas of the brain in individuals with mild TBI on days 11-16 to unfavorable outcomes at 3 and 6 months (18).
In summary, diffusion tensor imaging, or DTI, has shown the ability to detect diffuse axonal images and white matter changes in the brain associated with chronic mild TBIs. The protocols and areas most affected have shown some variability, but FA, or fractional anisotropy, has been the most consistent measurement affected. Current studies are aiming to uncover more about acute and chronic mild TBIs and to correlate these changes with clinical outcomes.
Most initial studies worked with working memory and Zhang and colleagues reported an abnormal disperse BOLD signal and increased activity in the dorsal prefrontal cortex (DLPFC) during a spatial memory task in concussed athletes (20). Talavage and colleagues showed significant changes on fMRI in eleven high school football players when comparing pre and postseason scans. Altered activation in the DLPFC and other fMRI changes were shown in both concussed and non-concussed players, suggesting that subconcussive blows or trauma may affect the brain with no observable symptoms and these players will continue to play (21). Three recent studies have also shown an decreased functional connectivity default mode network or resting state in patients suffering from persistent post-concussive symptoms (19, 22-23). Sours et al. also showed progressive DMN changes during the first 6 months following injury, which is suggestive of compensatory reorganization or disrupted network communication due to structural damage (23).
In summary, functional MRI and detection of aberrant BOLD signal shows promise as an indirect marker for altered neuronal activity in patient with mild TBI and persistent post concussive symptoms. Altered activity in the prefrontal cortex after both subconcussive trauma without symptoms and concussed athletes has been reported. The functional connectivity and default mode network seem to be affected in patients suffering from PPCS and may be used as an indicator or tool for concussion recovery.
For individuals with mild TBI, abnormal SPECT scans were shown to be predictive of poor clinical outcomes at 3 months and 12 months and normal SPECT scans had favorable clinical outcomes in the same timeframe (26). The American Academy of Neurology did issue caution with this study, however, due to lack of consensus or definition of an “abnormal” exam (27). A 2011 study showed significant decreases in regional CBF across the whole brain on SPECT in former NFL players when compared to age-matched controls. The areas most affected were the prefrontal poles, temporal poles, occipital lobes, anterior cingulate gyrus and cerebellum (28). Another 2015 study with 15 patients with chronic mild TBI showed larger areas of regional CBF during neuropsychiatric testing in the dorsolateral prefrontal cortex and areas of suppression in the occipital and parietal lobes when compared to asymptomatic subjects. It was also shown that patients with TBI showed correlations in the inferior frontal and superior temporal cortices during testing, whereas healthy controls had more activation in the cerebellar cortex. This was thought to suggest a compensatory mechanism and provide an explanation of cognitive fatigue and impairment in patients with chronic mild TBI (29). Other studies have focused on symptomatic subjects with chronic mild TBI and have shown hypoperfusion on SPECT imaging involving the frontal and temporal lobes, but these findings have not been consistently correlated with symptoms, clinical picture or performance on neuropsychiatric testing (30-34).
In summary, SPECT is a functional technique used to measure cerebral blood flow that produces tomographic or 3D images and has been shown to be more sensitive than conventional MRI or CT in detecting abnormalities with TBIs. A few studies have shown abnormal cerebral blood flow, most notably dorsolateral prefrontal cortex and temporal lobes, in multiple studies. However, more long term data regarding abnormal SPECT scans and their relevance in regards to clinical symptoms and outcome is needed.
Another modality called arterial spin labeling (ASL) uses electromagnetically labeled water molecules contained within the arterial blood in the neck and relies on radiofrequencies and is an attractive alternative for perfusion studies regarding TBIs. There is one 2009 study with ASL that showed a decrease in bilateral thalamic cerebral blood flow that was significantly correlated with neurological testing results (35). Another study in 2010 showed global CBF reductions, but worst particularly in the posterior cingulate cortices, the thalami and frontal cortices, in 27 patients with chronic TBI at resting state (36).
1. Pulsipher DT et al (2011) A critical review of neuroimaging applications in sports concussion. Curr Sports Med Rep 10(1):14–20
2. Parizel PM et al (2005) New developments in the neuroradiological diagnosis of craniocerebral trauma. Eur Radiol 15(3):569–81
3. Mittl RL, Grossman RI, Hiehle JF et al. Prevalence of MR evidence of diffuse axonal injury in patients with mild head injury and normal head CT findings. AJNR Am J Neuroradiol 1994; 15: 1583–1589 [18]
4. Gentry LR, Godersky JC, Thompson B, Dunn VD. Prospective comparative study of intermediate-field MR and CT in the evaluation of closed head trauma. AJR Am J Roentgenol 1988; 150: 673–682
5. Jordan BD. Acute and chronic brain injury in United States National Team Soccer Players. Am. J. Sports Med. 1996; 24(5):704Y5. 23.
6. Jordan BD, Zimmerman RD. Magnetic resonance imaging in amateur boxers. Arch. Neurol. 1988; 45(11):1207Y8.
7. Levin HS, Lippold SC, Goldman A, et al. Neurobehavioral functioning and magnetic resonance imaging findings in young boxers. J. Neurosurg. 1987; 67(5):657Y67.
8. Schrader H et al (2009) Magnetic resonance imaging after most common form of concussion. BMC Med Imaging 9:11
9. Morgan CD, Zuckerman SL, King LE, Beaird SE, Sills AK, Solomon GS. Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging. Child’s Nervous System. 2015;31:2305–2309
10. Inglese M, Makani S, Johnson G et al. Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study. J Neurosurg 2005; 103: 298–303
11. Hammoud DA, Wasserman BA. Diffuse axonal injuries: pathophysiology and imaging. Neuroimaging Clin N Am. 2002; 12: 205–216
12. Basser PJ, Jones DK. Diffusion-tensor MRI: theory, experimental design and data analysis V a technical review. NMR Biomed. 2002; 15(7Y8): 456Y67.
13. Mukherjee P, Miller JH, Shimony JS, et al. Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation. AJNR Am. J. Neuroradiol. 2002; 23(9):1445Y56.
14. Hughes DG, Jackson A, Mason DL, et al. Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery. Neuroradiology. 2004; 46(7):550Y8
15. Le Bihan D, Mangin JF, Poupon C, et al. Diffusion tensor imaging: concepts and applications. J. Magn. Reson. Imaging. 2001; 13(4): 534Y46
16. Morey RA, Haswell CC, Selgrade ES et al. Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans. Hum Brain Mapp. 2013;34(11):2986–2999
18. E.L. Yuh, et al. Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a TRACK-TBI study J. Neurotrauma, 31 (2014), pp. 1457-1477
19. Mayer AR, Mannell MV, Ling J, Gasparovic C, Yeo RA. Functional connectivity in mild traumatic brain injury. Hum Brain Mapp. 2011; 32: 1825–1835
20. Zhang K, Johnson B, Pennell D, et al. Are functional deficits in concussed individuals consistent with white matter structural alterations: combined fMRI and DTI study. Exp. Brain Res. 2010; 204(1):57Y70.
21. Talavage TM, Nauman E, Breedlove EL et al. Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion (abstract). J Neurotrauma. 2013
22. Sours C, Zhuo J, Janowich J, Aarabi B, Shanmuganathan K, Gullapalli RP. 2013. Default mode network interference in mild traumatic brain injury – A pilot resting state study. Brain Research 1537:201-215.
23. Sours, C, Chen, H.; Roys, S.; Zhuo, J.; Varshney, A.; Gullapalli, R.P. Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients. Brain Connect. 2015, 5, 442–450.
24. Bergsneider M, Hovda DA, McArthur DL et al. Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability. J Head Trauma Rehabil 2001; 16: 135–148
25. Hofman PA, Stapert SZ, van Kroonenburgh MJ, Jolles J, de Kruijk J, Wilmink JT. MR imaging, single-photon emission CT, and neurocognitive performance after mild traumatic brain injury. AJNR Am J Neuroradiol 2001; 22: 441–449
26. Jacobs A, Put E, Ingels M, Put T, Bossuyt A. One-year follow-up of technetium99m-HMPAO SPECT in mild head injury. J Nucl Med 1996; 37: 1605–1609
27. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment of brain SPECT. Neurology. 1996; 46: 278–285
28. Amen DG, Newberg A, Thatcher R et al. Impact of playing American professional football on long-term brain function. J Neuropsychiatry Clin Neurosci 2011; 23: 98–106
29. Hattori N, et al. Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury. J Nucl Med. 2009;50:1054–1061
30. Umile EM, Plotkin RC, Sandel ME. Functional assessment of mild traumatic brain injury using SPECT and neuropsychological testing. Brain Inj. 1998; 12: 577–594 [77]
31. Bonne O, Gilboa A, Louzoun Y et al. Cerebral blood flow in chronic symptomatic mild traumatic brain injury. Psychiatry Res. 2003; 124: 141–152
32. Ichise M, Chung DG, Wang P, Wortzman G, Gray BG, Franks W. Technetium99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: a correlation with neuropsychological performance. J Nucl Med 1994; 35: 217–226
33. Kant R, Smith-Seemiller L, Isaac G, Duffy J. Tc-HMPAO SPECT in persistent post-concussion syndrome after mild head injury: comparison with MRI/CT. Brain Inj. 1997; 11: 115–124
34. Umile EM, Sandel ME, Alavi A, Terry CM, Plotkin RC. Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability. Arch Phys Med Rehabil 2002; 83: 1506–1513
35. Ge Y, Patel MB, Chen Q et al. Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3 T. Brain Inj. 2009; 23: 666–674
