I’m on my back, trapped inside a big plastic tunnel, two firm pads locking my head in place.
Looking up, a mirror angled at 45 degrees allows me to see out of this confining tube to a glass window behind which I see a technician. I imagine he’s punching buttons to fire up the massive magnet that surrounds me.
Then, the machine groans to life: a series of clicks, snaps and rumbles in a strange, almost musical experience akin to a surround-sound Kraftwerk album being blasted at me from all directions.
I’m having an MRI scan.
The reason? I suffered a whiplash injury after being dumped into the ground playing footy. While I was cleared of any dangerous traumatic brain injury – a TBI – I had continuing neurological symptoms in the weeks after the incident and my doctor decided to double-check for any signs of spinal damage.
After 25 minutes of being photographed in a strong magnetic field, the images of my spine produced by the MRI cleared me of serious damage.
In many settings, an MRI – capable of showing the blood flow, damage or change within these structures – is the go-to for emergency doctors and GPs to assess the brain and spine after a head injury. MRI and CT scans are useful tools to rule out severe brain injury.
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Yet diagnosing concussion and mild TBI isn’t like identifying COVID-19 off a nasal swab, or a broken limb where an X-Ray confirms the diagnosis. Sometimes, conventional scanning is insufficient to understand the physical and chemical changes of brain injury.
Atop this, no two concussions are the same. A mild TBI might be recoverable in a fortnight for some, but for others, symptoms may persist for weeks, months, maybe even longer. So, finding what causes ongoing symptoms and the potential for long-term brain disease is the holy grail for neuroscientists researching brain function and injury.
“Concussion is a very complex condition,” says Dr Fatima Nasrallah, a neuroscientist from the Queensland Brain Institute.
“It’s a dynamic condition. We’re still scraping the surface in terms of understanding what concussion effects appear like in the brain.”
If concussion and mild TBI don’t show up in conventional scans, then more powerful tools are required.
Nasrallah is a neuroscientist whose research uses functional MRI as a window into studying the workings of healthy brains, and how they’re impacted by injury.
Functional scanning looks at how different regions of the brain speak to each other, identifying points of disruption or change over time, and helping inform clinicians of pathways to manage injury.
That’s distinct from most imaging techniques used in most hospitals, which “tell you whether there’s something that’s disrupted in a specific area” but don’t look at how brain activity is altered by changes associated with blood flow within it.
In conventional scans, the brain might appear normal after a mild TBI, in contrast to a severe injury where trauma is likely visible.
“So how do you identify with an evidence base, rather than just relying on symptoms, how the brain is affected?” Nasrallah says.
Enter biomarkers.
The hunt for symbols of damage
The efforts of researchers to identify a definitive blood biomarker – the concussion equivalent of identifying COVID-19 in a nasal swab – is needle-in-a-haystack stuff.
But it will be the difference between waiting for death to autopsy the brain, and being able to definitively diagnose neurodegenerative brain injuries like CTE while a person is alive.
“There is a great need for reliable biomarkers,” says Australian Sports Brain Bank executive director Associate Professor Michael Buckland.
“At this stage, we have to wait till you’re dead to receive a definitive diagnosis, because we need to examine large amounts of the brain to make the diagnosis under the microscope.”
Biomarkers are signifiers of disease or other clinically significant changes in the body. They can range from measurements of blood pressure to medical imaging of the body, to tiny molecules found circulating in blood and bodily fluids, to genetic variations.
Take low-density lipoprotein (LDL) which is, in layperson’s terms, ‘bad’ cholesterol. A high LDL reading is used to inform clinicians of the potential for arterial plaque buildup, which could lead to a future heart attack or stroke.
Genetic testing can also chalk up a list of problem mutations that might lead to inheritable disease. Some genes are associated with disorders like cystic fibrosis, haemophilia, polycystic kidney disease, certain cancers and a range of autoimmune problems.
And there are potential biomarker candidates that exist when the head experiences trauma.
In brain impact injuries, the blood-brain barrier is disrupted and chemicals are released into the bloodstream that would not normally be there. A brain trauma specific biomarker – a chemical acting as a signifier of injury or recovery – would provide a far superior tool for patient management than arbitrary no-play periods or CT scans.
Functional imaging can be used to guide and monitor injury recovery by comparing structural and functional damage to a baseline and, at least, monitoring how blood markers change as the brain heals.
“This gives us a really, really good really good view of how the markers correlate with what we’re seeing in the brain and how they change over time… identifying when that person is recovered,” Nasrallah says.
“You might say the clinical symptoms [things like headaches and blurred vision] recover at five days, but then we have a marker in the blood which says you’ve recovered at 15 days, and those [are] where we see that the MRI scan shows structural or functional damage has come back to baseline.”
There are barriers in the way of neuroscientists identifying one – or several – appropriate biomarkers for concussion and mTBI: when, where and for how long do biomarkers appear in the blood? And what about how those biomarkers enter the blood? While ruptures in the blood-brain barrier are likely to lead to chemicals entering circulation, it’s not always the sole point of biomarker release. Any injury, Nasrallah says, triggers a whole-of-body response.
“When we measure these biomarkers from the blood, they don’t only measure a change to the brain, they measure a change to what’s happening in other parts of the body as well, and that’s where they become a little bit nonspecific,” she says.
This challenge emphasises concussion and mTBI as “multi-traumatic” injuries affecting multiple parts of the body. In a body-wide bloodstream, biomarkers observed in a brain scan might be released from elsewhere in the body. This uncertainty, which faces Nasrallah and other neuroscientists, needs to be overcome.
There are other challenges in diagnostics: gender and age also play a role.
Classically, most high-contact sport participants have been male. Now, females are entering more concussion-prone pursuits at increasingly professional levels. Athletes are also playing to later ages and entering elite development pathways while younger.
Everyone talks about concussion in sport, but there’s more to it than that
Scientists therefore have the challenge of ensuring any hypothetical gold-standard biomarker applies across all demographics. That means getting relevant data from a greater cross-section of athletes.
“We are now seeing that potential biomarkers act quite differently in males and females, and in people of different ages,” says Dr Sarah Hellewell from the Perron Institute and Curtin University.
“Incorporating more diverse samples has been a step forward but still remains a challenge: it’s hard to study people who have just had a concussion outside of sports because most people don’t go to hospital, and many don’t seek any medical care at all.”
Next: The tech to detect
Editor’s note: We have updated the position title for Associate Professor Michael Buckland
