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BGU researchers develop MRI test that detects degenerative brain disease in athletes

Typical brain images from a American football player (right) and a non-player control. The colored regions show brain areas with a leaky BBB. Note that the player brain shows more leaky brain regions compared to the non-player healthy control. (Photo Credit: Prof. Alon Friedman)
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Using brain imaging techniques and analytical methods, the researchers could determine if football players have chronic traumatic encephalopathy (CTE) by measuring leakage of the blood-brain barrier

By ILANIT CHERNICK

Researchers at Ben-Gurion University have developed the first MRI test that can detect a neurodegenerative disease caused by repeated head injuries that often affects athletes who play contact sports.

The disease, chronic traumatic encephalopathy (CTE) can only be diagnosed through brain tissue analysis post-mortem. However, in a new study, the researchers present a new test methodology. Using brain imaging techniques and analytical methods, they can determine if football players have CTE by measuring leakage of the blood-brain barrier.

According to the authors, the blood-brain barrier (BBB) is a specialized interface between the blood and the brain environment that prevents the transfer of unwanted molecules or infectious organisms from the blood to the brain. Evidence shows that breaching the integrity of this barrier causes many brain diseases and neurodegeneration as a result of aging.The study included 42 Israelis who play amateur American football in the Israeli Football League and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. 

MRI’s were also performed on 51 patients with malignant brain tumors, ischemic stroke or traumatic brain injury. 

The NFL sideline concussion assessment tool was used to document history of previous head injuries, including concussions, as well as symptoms assessment and Standardized Assessment of Concussion (SAC) tests.

Prof. Alon Friedman, a neurosurgeon and researcher at BGU and Dalhousie University in Canada, explained that “since a leaky BBB is also found in CTE and causes brain dysfunction and degeneration, it now seems that this test could provide the first (and so far the only) evidence for brain injury in the players we studied on the Israel football team.

“Importantly, we believe that those with persistent leakage encompassing months or years are more likely to develop CTE,” he said. “Many players seem to repair their BBB quickly, and if they do not suffer from repeated traumatic brain injuries or are not sensitive to brain injury, they are not likely to develop CTE.”

As part of the study, the researchers then developed a modified dynamic contrast-enhanced-MRI (DCE-MRI) protocol and analytical methods to investigate vascular pathology and blood-brain barrier disorder (BBBD) associated with repeated mild TBI in American football players.

“For the first time, using human brain imaging, they distinguished between fast and slow leakage through the pathological BBB and showed that localized, specific post-traumatic vascular pathology may persist for months in a subset of players,” BGU said.

Asked about the process, Friedman said the researchers “generated maps that visualized the permeability value for each 3D section,” otherwise known as the voxel.

“Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in the control group,” Friedman continued. “The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with alterations in white matter tracts. Importantly, increased permeability persisted for months, as seen in players who were scanned both on- and off-season.”

He also pointed out an important observation that the few players who did not complain of severe symptoms also showed a leaky BBB. 

“This suggests that DCE-MRI should be used in conjunction with symptom questionnaires before return to play is approved,” Friedman stressed.

The researchers also emphasized that football players were three times more likely to display a leaky BBB, explaining that blood-brain barrier disorder was detected in 27.4% of players. 

This suggests, the authors wrote, that it could clarify the wide range of cognitive deficits and neuropsychiatric impairments observed in players,

“Our findings show that DCE-MRI can be used to diagnose specific vascular pathology after traumatic brain injury and other brain pathologies,” Friedman added.

The researchers noted that while the present study was performed in otherwise-healthy amateur players, future studies are recommended to determine the prevalence and spatial-temporal characteristics of BBBD in professional players and/or retired players with and without CTE clinical signs and symptoms.

The authors stressed that if differences are found, may improve the understanding of the effects of impact strength and frequency, age of onset, player’s skill and extent of vascular injury.

This study is a collaboration among researchers from the BGU Blood-Brain Barrier Lab, UC Berkeley, Boston University, Dalhousie University, and Trinity college in Dublin.

The study was published in Brain: A Journal of Neurology.

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