Can we use functional and metabolic imaging to diagnose concussion?

This week, Physiotherapist Theo Farley explores imaging modalities in the diagnosis of concussion.

Welcome to the sixth episode of The Concussion Blog. This week we’re going to consider imaging modalities in the diagnosis of concussion. 

We know from the literature that concussion is a ‘functional’ rather than a ‘structural’ injury which is why conventional structural MRI, although useful for ruling out potentially life threatening pathology, doesn’t help us in concussion diagnosis.

We’re going to look at a review by Shin and colleagues who reviewed current functional and metabolic imaging modalities for mild TBI/concussion and discussed their merits. 

Shin SS, Bales JW, Edward Dixon C, Hwang M. Structural imaging of mild traumatic brain injury may not be enough: overview of functional and metabolic imaging of mild traumatic brain injury.Brain Imaging Behav. 2017 Feb 13. [Epub ahead of print]

Axonal injury is known to take place following brain injury however it is now believed that this doesn’t only take place at the time of impact but the following crescendo of molecular changes with in the brain causes further damage. At the time of impact, alignment of the neurofilaments is disrupted and there is a development of focal swelling along the axonal tract (1). The subsequent influx of calcium and resultant activation of proteases causes further neuronal damage. This process leads to impaired axonal transport and eventual disconnection at the injury site along the axon.

Having said that not all neuronal damage leads to neurone shearing and concussive symptoms have in some studies been found not to correlate with the appearance of imaging techniques such as Diffusion Tensor Imaging despite evidence that this technique does detect axonal damage.

All of this is picked up at a histological level in a lab setting so how do we gain this level of insight in a clinical setting? Non-invasive imagining techniques are now advancing and some can observe subtle changes at a molecular level so lets take a look at the pros and cons of these techniques.

Here’s where your inner geek is about to get excited…

Positron emission tomography (PET)

PET imaging (bottom image) uses a radioactive tracer to detect changes the in metabolic levels of the brain. As the radioactive labeling agent is composed of glucose it is taken up where higher levels of metabolism exist. Conversely where there is reduced or no neuronal activity, metabolism is lower which shows up on the PET scan as reduced uptake of radioactive tracer. 

Acute time points taken post injury usually show significant increases in metabolic activity immediately post injury, followed by a reduction in metabolic activity following some hours(6).

Decreased cerebral metabolism has also been found through PET imaging among boxers who reports repetitive sub concussive impacts.

Single photon emission computed tomography (SPECT)

SPECT scans use gama ray omitting isotope to detect cerebral blood flow  (CBF) levels. The isotope is injected to the patients blood stream with the uptake of the agent calculated as a proportion of CBF. It is well documented that cerebral blood flow is reduced following concussion as part of the energy crisis and has been shown to last for up to 30 days post injury, long after clinical symptoms have resolved.

The use of SPECT scans in the diagnosis of concussion have been advocated for their cost effectiveness and their ability to detect changes in CBF without the need for axonal damage. In a report of 43 mTBI patients at a mean interval of 1.3 years 53% of patients using SPECT had abnormal results, whereas 9% of patients using MRI and 4.6% of patients using CT scans had abnormal findings(2).

Reduced CBF has been picked up on SPECT within 24 hours of injury. One prospective study analyzing 136 patients showed that persistent abnormalities in SPECT signals over 12 months were associated with post concussive symptoms(3). Specifically, frontal cortex hypoperfusion was associated with post concussive symptoms.

Function magnetic resonance imaging (FMRI)

FMRI (top image) is concerned with blood flow in the brain and again detects neuronal activity through increased metabolic demand and consequent increase in blood flow. Additionally, the release of oxygen from hemoglobin and its subsequent change to deoxyhemoglobin leads to a change in the molecules magnetic properties. This change can be detected by a method called blood oxygen level dependent (BOLD) contrast imaging. FMRI studies use this principle to detect activity changes in different regions of the brain at either resting state or with specific tasks.

Electrophyiological assessment tool (EEG)

Although the EEG is not an imaging tool it was included in this study due to its widespread use. EEG allows for non invasive investigation of cerebral function through the placement of electrodes that measure the differences in electrical potential between two points.  This usually involves 21 scalp electrodes arranged according to The International 10-20  system.  

EEG is more commonly used in the assessment of patients with mild or severe TBI and has only been sparingly used in patients with mild TBI/concussion. 

Conventional EEG findings in TBI patients include generalised or focal slowing and attenuated alpha response, allowing for detection of abnormal electrical patterns. Although there are a limited number of findings in mTBI, there is an association with worse recovery from TBI in patients who have pathological findings on EEG within the first 24 hours after mTBI (2).

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Discussion

Concussion diagnosis and optimum time to return to play are two of the most pertinent and baffling questions in sports medicine at the moment. Although there are some promising findings coming from these imaging techniques we remain in the dark when it comes to being able to rely on one test/bio marker/imaging technique to definitively diagnose concussion and accurately inform the MDT on return to play.

What the techniques that we’ve looked at do give us is information to add to the rest of our concussion assessment and in doing so give additional confidence to us and validity to our decision making if and when challenged by players, parents and coaching staff.

It seems to me from this review that the heaviest weight of evidence is behind the assessment of cerebral blood flow offered by the SPECT scan, and functional MRI that demonstrates oxygen metabolism at the hemoglobin through BOLD contrast imaging. 

Stay in touch:

Twitter @Theo_Farley 
Email [email protected]

References

  1. Grady, M. S., McLaughlin, M. R., Christman, C. W., Valadka, A. B., Fligner, C. L., & Povlishock, J. T. (1993). The use of antibodies targeted against the neurofilament subunits for the detection of diffuse axonal injury in humans. Journal of Neuropathology and Experimental Neurology, 52(2), 143–152.
  2. Hessen, E., & Nestvold, K. (2009). Indicators of complicated mild TBI predict MMPI-2 scores after 23 years. Brain Injury, 23(3), 234–242.
  3. Jacobs, A., Put, E., Ingels, M., Put, T., & Bossuyt, A. (1996). One-year follow-up of technetium-99 m-HMPAO SPECT in mild head injury. Journal of Nuclear Medicine, 37(10), 1605–1609.
  4. Kant, R., Smith-Seemiller, L., Isaac, G., & Duffy, J. (1997). Tc-HMPAO SPECT in persistent post-concussion syndrome after mild head injury: comparison with MRI/CT. Brain Injury, 11(2), 115–124.
  5. Provenzano, F. A., Jordan, B., Tikofsky, R. S., Saxena, C., Van Heertum, R. L., & Ichise, M. (2010). F-18 FDG PET imaging of chronic traumatic brain injury in boxers: a statistical parametric analysis. Nuclear Medicine Communications, 31(11), 952–957.
  6. Zhang, K., Johnson, B., Pennell, D., Ray, W., Sebastianelli, W., & Slobounov, S. (2010b). Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study. Experimental Brain Research, 204(1), 57–70.