Chronic traumatic encephalopathy presents with a myriad of symptoms in a select cohort of people, making it difficult to diagnose and impossible to predict. To make matters worse, there is currently no accepted method to diagnose CTE in a living person.
In a new study, researchers from Ben-Gurion University (Israel) propose a solution to both problems: use dynamic contrast-enhanced-MRI (DCE-MRI) to image and measure leakage of the blood brain barrier (BBB). While breaching the integrity of the BBB is known to cause neurodegeneration, it’s role in CTE diagnosis was not previously understood.
According to his study, published in Brain, Alon Friedman, M.D., a neurosurgeon and researcher at BGU, thinks a person’s natural ability to repair their BBB quickly—or not—explains the variability in CTE symptoms and diagnosis among the overall population, and even sub-populations.
“Our data showing persistent leaky BBB in young, active American football players, suggest that this early pathology could serve for early diagnosis and monitoring of players at high-risk of developing delayed complications,” said Friedman. “Many players seem to repair their BBB quickly, and if they do not suffer from repeated TBIs or are not sensitive to brain injury, they are not likely to develop CTE.”
For the study, Friedman and his team employed a modified DCE-MRI method in combination with custom mapping. They scanned 42 Israelis who played amateur American football in the Israeli Football League (IFL), and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. The researchers also performed MRI scans on 51 patients with brain pathologies involving the BBB, namely malignant brain tumors, ischemic stroke or TBI. Then then generated maps that visualized the permeability value for each brain section.
According to the study results, a leaky BBB was found in 27% of scanned football players. Compared with controls, football players were 3x more likely to display a leaky BBB. The permeability maps revealed an increase in slow blood-to-brain transport in the subset of afflicted football players. The results mark the first time, using brain imaging, that researchers have been able to distinguish between fast and slow leakage through the BBB. However, the results still showed a large degree of inter-individual variability regarding who develops CTE and who does not.
To further explore this, Friedman and his team employed two animal models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. Both models showed slow blood-to-brain transport, which correlated with neuropathological changes.
“The differences found in controlled animal experiments suggest that variations in location, extent, timing, frequency and cumulative exposure of head injuries may not be the only explanation for inter-individual variability,” the paper reads.
While there may be variability between individuals, the permeability mapping suggests the slow transport of blood to the brain is actually region-specific and linked to changes in white matter. In the past 20 years, researchers have been gradually uncovering the role of white matter—or lack thereof—in neurodegenerative diseases like Alzheimer’s and CTE (which share many pathological characteristics).
The study authors note that future studies should investigate genetic differences in response to trauma, as a possible mechanism for inter-individual variability. Additionally, next steps could include determining the prevalence and spatial-temporal characteristics of BBB disorder in professional players and/or retired players with and without CTE clinical signs and symptoms. Differences, if found, may improve the understanding of the effects of impact strength and frequency, age of onset, player's skill and extent of injury.