Images of a Hard-Hitting Disease

Brain damage: Sections of the brain of a normal 65-year-old are shown at top; the brain of John Grimsley, a 45-year-old former NFL player is at bottom. The brown stain in Grimsley’s brain indicates large amounts of abnormal tau protein.
Credit: BU

Biomedicine

Images of a Hard-Hitting Disease

Advanced imaging techniques could help diagnose the degenerative brain disease linked to repetitive head trauma.

It is estimated that football players can receive as many as 1,500 hits to the head in one season. Not every blow results in immediate injury, but a growing body of research suggests that repetitive hits can lead to serious, long-term brain damage. More than 20 NFL players have so far been diagnosed with chronic traumatic encephalopathy (CTE), a neurodegenerative disease, after their deaths.
Researchers at Boston University's Center for the Study of Traumatic Encephalopathy (BU CSTE) are now using sophisticated imaging techniques to detect signs of this damage in living patients, work that could lead to a better understanding of the phenomenon, and help identify at-risk athletes. CTE is currently diagnosed through examining a patient's brain tissue under a microscope.
In February, the BU researchers examined the brain of Dave Duerson, a retired pro football player who committed suicide after suffering from symptoms tied to repetitive brain trauma, including memory loss, poor impulse control, and erratic behavior. Duerson, who played 11 seasons in the NFL, became the 14th player diagnosed with CTE out of the 15 NFL players the center has studied.
"CTE is becoming a widely recognized disease; it is part of the expanding knowledge of traumatic brain injury that has exploded in the last few years," says Julian Bailes, professor and chairman of the department of neurosurgery and the director of the Brain Injury Research Institute (BIRI) at West Virginia University, the only other institute studying the disease. "We don't yet know how big the problem really is—is it a few percent of players that have the disease, or more than that?" Bailes says.

In collaboration with Brigham and Women's Hospital in Boston, the BU researchers recently conducted a pilot study, which involved imaging the brains of five professional athletes known to have experienced repetitive head trauma, and five age-matched nonathlete subjects without any history of head trauma. A similar, but much larger, three-year study is expected to start this summer.
CTE is marked by the progressive degeneration of brain tissue and the accumulation of tau protein, which provides structural support for the microtubules that transmit molecules between cells and neurons, down the axonal tracks. It's thought that repetitive hits to the head cause these microtubules to stretch, swell, and fall apart, so the cell can't function and the tau protein starts clumping together.
The researchers used different imaging techniques to detect these changes in the brain. They used diffusion tensor imaging (DTI), a variation of magnetic resonance imaging (MRI), to examine the complex network of nerve fibers that connect different brain areas. DTI tracks the movement of water molecules through the brain, so researchers can create a detailed picture of the axons by analyzing the direction of water diffusion.
The researchers saw fewer axonal connections between neurons and fibers in the pilot study subjects who had a history of head impacts. "It was very apparent when we put the images side by side that the athletes have advanced atrophy or areas where fiber tracks have disappeared," says Christopher Nowinski, codirector of CSTE and co-founder and president of the Sports Legacy Institute, a nonprofit organization based in Waltham, Massachusetts, that studies brain injury in athletes and was involved with the project.

mages of a Hard-Hitting Disease

(Page 2 of 2)

• Thursday, May 19, 2011
• By Brittany Sauser

Suicidal damage: Above are three sections of the brain of Dave Duerson, a 50-year-old former NFL player who committed suicide in February—the frontal and temporal cortex, hippocampus, and amygdale. The brown, discolored areas show large amounts of abnormal tau protein, an indication that Duerson had moderately advanced CTE. The bottom row shows microscopic images from the abnormal brain regions.
Credit: BU

The researchers also used magnetic resonance spectroscopy (MRS), a technique that measures levels of chemicals and neurotransmitters in the brain. "It's like a virtual biopsy of the brain, because we get to see a spectral analysis of various biochemical metabolites without invasively going into it," says Robert Stern, co-director of CSTE and an associate professor of neurology at BU School of Medicine. "The study showed some very striking and significant differences between the athletes and the controls when it comes to certain chemicals," Stern says. He did not want to comment on the specific chemical differences, however, because it was only a pilot study.
The brains of all five of the athletes' with a history of head impacts were abnormal in one way or another, says Nowinski. But this does not necessarily mean that the subjects have CTE. "That is the point of the larger study, to figure out if the abnormalities mean anything," he says.
The larger study will include a group of retired NFL players that the researchers consider to be at the greatest risk of developing CTE, and a group of retired athletes that played noncontact sports and have no history of repetitive brain injury. In addition to imaging players' brains using DTI, MRS, and advanced MRI, the researchers will take DNA, blood, and spinal fluid samples to look for genetic risk factors. They will also conduct clinical and neurological examinations and neuropsychological tests. The disease symptoms include memory problems, impulse control, depression, apathy, and problems with cognitive skills like planning.
"While we know that repetitive brain trauma is a necessary variable, it is not a sufficient variable," says Stern. In other words, the researchers don't know why some people who experience repetitive brain trauma get the disease while others do not, and they don't know how many hits, or what types of hits, may cause the disease.
By combining different tools, the BU researchers expect to be able to detect and diagnose CTE within five years. CSTE has over 73 brains in its brain bank, with over 360 athletes committed to donating theirs after they die. Stern also confirmed that the center is receiving the brain of 28-year-old NHL player Derek Boogard, who was found dead in his apartment on May 13. He was recovering from a season-ending traumatic brain injury. The center has also found evidence that the two former NHL players it has examined had CTE.
"Advanced imaging techniques are the future of early diagnosis," says Gunnar Brolinson, associate dean for clinical research for the Virginia College of Osteopathic Medicine and the physician for Virginia Tech's football team. Until then, Brolinson says, "you have to take the head out of the game by making better rules and educating players, coaches, and parents on head injuries."
The NFL made significant rule changes last season with this in mind—harsher penalties and heavy fines for helmet-to-helmet hits or hits against defenseless players.