Episode 64 of Ask Concussion Doc with Dr. Cameron Marshall, discusses concussion in relation to medical imaging modalities; the role they play in the assessment and treatment of concussions, and what they can and cannot show.
Concussion injuries are part of the overall continuum of Traumatic Brain Injury (TBI). Synonymous with the term Mild Traumatic Brain Injury (mTBI), concussion is a functional injury, meaning the structure of the brain remains intact, whilst moderate and severe TBI’s are indicative of structural damage.
So, what does the term “functional injury” actually mean?
Concussions occur following a sudden acceleration and deceleration of the brain within the skull, either due to a direct blow to the head or elsewhere on the body whereby the forces are transmitted to the brain. This mechanism causes deformation of the cell membranes (ie. stretch and sheer theory) resulting in the movement of molecules in and out of the axons, ultimately causing depolarization or rapid firing of the affected neurons and a resulting energy deficit rather than any structural damage.
The injury mechanism described above is the reason structural imaging modalities, such as CT and MRI scans, cannot show evidence of concussion. However, these modalities may still be utilized when being assessed for a concussion to rule out the possibility of more serious pathology such as a bleed on the brain.
A functional injury means that evidence of the injury is attributed to functional changes. This may be inclusive of both symptoms of concussion and alterations in a persons ‘normal’ functioning such as cognitive tasks like memory, balance, reaction time, visual motor skills and more. These functional changes are often assessed through clinical means throughout recovery such as physical testing by a medical rehab professional.
What are “Functional Imaging Modalities” and what value can they add to concussion care?
Functional imaging modalities are those that look further at tissue function as oppose to the structures of which they are made up of. A summary of the various functional imaging modalities has been detailed below.
Types of Functional Imaging Modalities
Functional MRI (fMRI) – Looks at blood oxygen levels or oxygen usage in tissues based on the flow of blood or oxygen in a certain area of the brain. An example of this is when tissues or an area of the brain is more active, blood will be shunted to the area and appear as a hot signal on fMRI. There are two types of fMRI including resting state and task-based fMRI.
fMRI is very non-specific to concussion; patterns seen in concussion patients have been found to be similar to those seen across multiple conditions including anxiety, chronic stress, PTSD, chronic pain and more. This raises the issue of what the patterning actually represents, for example is the patterning caused by a concussion or any number of the other listed conditions. When compared to normal healthy individuals’ differences in patterning will be seen, however since the origin of the altered patterns cannot be discerned from other causes fMRI cannot be used as a diagnostic tool for concussion.
Single Positron Emission CT Scan (SPECT) – A CT scan with a radioactive nucleotide or tracer injected into the body. Once injected into the blood stream the tracer follows the blood vessels, showing blood flow in various tissues. Changes in blood flow in the brain or decreased cerebral (brain) perfusion have been indicated in concussion patients with persistent symptoms for up to 5 years following injury. However, similar findings have also been found in patients with low back pain, neck pain, whiplash, upper back pain, depression, chronic fatigue and more. Therefore, these changes could be indicative of any number of the above conditions and it is impossible to determine the causative factor through SPECT imaging.
Diffusion Tensor Imaging (DTI) – looks at the white matter or axon tracts of the brain, via the flow of water molecules or diffusion that is either in alignment with or perpendicular to an axon.
If an axonal tube is intact and undamaged it is theorized that water will flow only in alignment rather than perpendicular, resulting in a parallel diffusion pattern. In the event of injury, the theory is that axonal swelling would result in haphazard water movement or a breakdown of the protective myelin sheaths (preventing the containment of water), resulting in perpendicular or radial diffusion patterns and hence less one directional flow. Although not evidenced on MRI or CT scans, DTI is thought to show this type of micro-structural or internal cellular damage, which is promising due to the theory of concussion resulting from a deeper axonal injury.
The clinical utility of DTI has been brought into question by some studies in recent years, with a systematic review by Asken et.al. in 2018 discovering similar findings on DTI in both post-concussion patients and patients with either low socio-economic status, major depressive disorders, or ADHD.
Another study by Wild et.al. in 2018 found the following – “When compared to an orthopedically injured group, concussion showed no differences in diffusion metrics within 96 hours or 3 months after injury, however both groups (concussion and orthopaedic) showed differences from controls. Injury in general may cause changes in their diffusion metrics, pain may cause changes in their diffusion metrics.”
“Overall the results indicate that both groups of patients with traumatic injuries regardless of whether the injury resulted in head injury, exhibited similarly altered sub-acute diffusion differences in the white matter regions compared with the non-injured comparison group and that these differences generally persisted 3 months later. It may be that trauma related issues obscure or confound differences that are attributed to head injury itself.”
From the above studies it can be concluded that DTI should not yet be utilized to assist diagnostic, prognostic or management decisions; as with other functional imaging, changes could be indicative of any number of causes beyond concussion.
Magnetic Resonance Spectroscopy – An MRI technology that looks at tissue metabolites. Specifically related to concussion is the metabolite N-Acetyl-Aspartate (NAA), due to its high correlation with ATP or the energy molecule in the brain. As concussion results in increased neuronal firing in the brain followed closely by a reduction in energy molecules, the ability to measure energy levels is highly relevant. As ATP cannot be directly measured in live subjects, one of the best measures to discern these changes is via the molecule NAA. The valuable information here is the ability to see the reduction in energy immediately after concussion followed by the gradual recovery of metabolites to normal levels. Many of the animal studies completed in this area have found the immediate low energy phase to be the phase in which the brain is extremely vulnerable. The question then becomes when we are recovered from this vulnerability and hence when it is safe to return to full contact sporting activity.
A few large studies completed in Italy have indicated the metabolic recovery period to take anywhere from 22 to 30 days while others showed as long as 45 days, however due to the potential variability across cohorts it is difficult to determine a range. What is known is that metabolic recovery is longer than the previously thought 7 to 10 days where symptoms are usually present.
One issue with this type of imaging is the limited amount of research and hence it is unknown what other conditions could cause similar findings. It is known that stroke and/or damage to the brain can cause energy drops also, however it is unknown if conditions such as depression would produce the same results. The technique is also quite difficult to interpret and as such has created a barrier and limitation on further research in the field.
Positron Emission Tomography (PET) – Another type of CT scan with an injected radionucleotide which bind to specific compounds causing them to light up on the scan. This type of imaging is being explored in relation to the more long-term effects of concussion.
The radionucleotide of interest for concussion is FDDNP, which binds to TAU proteins. TAU protein is the protein that has been found in both Alzheimer’s and CTE patients, along with a number of other conditions. Currently CTE is purely a post-mortem diagnosis (ie. autopsy), and the hope is that with enough research these findings can be confirmed with the goal of eventually being able to diagnose CTE in life, however a lot more research is required.
There are many different types of imaging available as described above. Structural scans such as MRI and CT are not used in relation to the diagnosis of concussion, however, may be used to rule in or out more sinister pathologies such as structural damage to brain as seen with moderate and severe TBI’s. Functional imaging techniques such as fMRI, SPECT, DTI, MR Spectroscopy and PET scans are all considered to be research only tools, as there is still not enough known about the variety and patterning to be clinically useful. As such, concussion remains a clinical diagnosis, meaning that the diagnosis of this type of injury is based on the underlying mechanisms driving clinical symptoms as oppose to any kind of structural damage that can be evidenced by imaging.
References
Asken, B.M., DeKosky, S.T., Clugston, J.R. et.al. (2018). Diffusion tensor imaging (DTI) findings in adult civilian, military, and sport-related mild traumatic brain injury (mTBI): a systematic critical review, Brain Imaging and Behaviour, 12: 585-612.
Vagnozzi, R., Signoretti, S., Cristofori, L., et.al. (2010), Assessment of metabolic brain damage and recovery following mild traumatic brain injury: A multicentre proton magnetic resonance spectroscopic study in concussed patients, Brain A Journal of Neurology, 133: 3232-3242, doi:10.1093/brain/awq200
Wild, E.A., Ware, A.L., Xiaoqi, L., et.al. (2018), Orthopaedic injured versus uninjured comparison groups for neuroimaging research in mild traumatic brain imaging, Journal of Neurotrauma, 36(2): 239-249.
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