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Using an advanced imaging technique, researchers at Albert Einstein College of Medicine and Montefiore Health System were able to predict which patients who’d recently suffered concussions were likely to fully recover. The study also sheds light on the brain’s mechanisms for repairing or compensating for concussion injuries—information that could speed the development of therapies. The study was published online today in the American Journal of Neuroradiology.
“Our study presents for the first time a precision approach to harness imaging at the time of concussion to forecast outcome a year later,” said study leader Michael L. Lipton, M.D., Ph.D., professor of radiology, of psychiatry and behavioral sciences, and of neuroscience, as well as associate director of the Gruss Magnetic Resonance Research Center (MRRC) at Einstein and director of MRI services at Montefiore. “While we still lack effective treatments, we now have a better understanding of the neurological mechanisms that underlie a favorable response to concussion, which opens a new window on how to look at therapies and to measure their effectiveness.”
Each year, 2.5 million people in the United States sustain traumatic brain injuries (TBI), according to the Centers for Disease Control and Prevention. Concussions account for at least 75 percent of these injuries. Diagnosing concussion is based on assessing symptoms.
“While most people think of concussions as a mild and short-lived injury, 15 to 30 percent of patients are left with symptoms that persist indefinitely,” said Sara Strauss, M.D., the study’s lead author and resident in the department of radiology at Montefiore. “Until now, we haven’t had a reliable way to differentiate in advance those who may be burdened long-term and those who would have a complete recovery.”
Conventional imaging techniques, such as CT scans and MRI, cannot detect the subtle damage to axons (the nerve fibers that constitute the brain’s white matter) that is associated with concussions. But in a previous study, Dr. Lipton and his colleagues demonstrated that an advanced form of MRI called diffusion tensor imaging (DTI) can detect concussion-related damage to axons. It does so by “seeing” the movement of water molecules along axons, which allows researchers to measure the uniformity of water movement (called fractional anisotropy, or FA) throughout the brain. Finding a low FA brain region, for example, indicates structural damage that has impeded water movement in that area.
In the current study, Dr. Lipton tested whether brain abnormalities identified on DTI of individual concussion patients could distinguish between those patients who will eventually recover and those who will not. DTI was performed on 39 patients diagnosed with mild TBI by an emergency room physician within 16 days of the initial injury and on 40 healthy controls. The DTI image of each patient was compared with images for the entire group of healthy controls to see where patients’ brains were abnormal. Patients were also assessed for three measures: cognitive function, post-concussion symptoms and health-related quality of life measures. A year later, 26 of the concussion patients returned for follow-up assessments.
DTI imaging comparing concussion patients and healthy controls revealed two types of white-matter abnormalities in patients: (1) areas of abnormally low FA (red, in associated image) that correlate with axon damage and the cognitive impairment that can affect concussion patients; and (2) other brain areas with abnormally high FA (blue) that may indicate where the brain has responded favorably to injury, perhaps by more efficiently connecting axons or by remyelinating injured tissue (i.e., forming fatty tissue around nerves, which allows nerve impulses to move more quickly).
The amount of high FA imaged in brains predicted patients’ outcomes following concussion. Having a greater volume of abnormally high FA white-matter areas (perhaps indicating good compensation for concussion damage) was associated with better outcomes on follow-up assessments. (This doesn’t mean that the low FA areas showing white-matter damage aren’t important—just that they’re not useful in predicting recovery from concussion a year later.)
“Being able to predict which patients have a good or bad prognosis has tremendous implications for discovering and evaluating treatments for concussion,” said Dr. Lipton. “Developing an effective intervention requires first identifying the people who need it. Seventy to 85 percent of concussion patients get better by themselves, which makes it difficult to learn whether any treatment is actually helping. Our imaging technique allows researchers to test potential therapies on those concussion patients who can truly benefit from them.”
Dr. Lipton noted that most therapies tried so far for TBI have focused on reducing damage from brain injury or preventing an injury from progressing, but none has proven effective. “Our findings,” he said, “suggest that it might be worthwhile to try a different strategy—namely, attempting to enhance the brain’s innate abilities to compensate functionally and structurally for whatever damage has been done.”
Dr. Lipton cautions that further studies are needed to validate this approach for predicting concussion outcomes. “While we were able to predict the outcomes for the patients in our study; more refined approaches—incorporating additional patient and injury characteristics, for example—may be needed when applying the test on widely differing individuals,” he said.
The study is titled, “Bidirectional Changes in Anisotropy are Associated with Outcomes in Mild Traumatic Brain Injury.” The other contributors are: S. B. Strauss, Namhee Kim, Ph.D., Craig Branch, Ph.D., M.E. Kahn, Mimi Kim, Sc.D., Richard Lipton, M.D., Jennifer Provataris, M.D., H.F. Scholl and Molly Zimmerman, Ph.D., all at Einstein.
The study was funded by grants from the National Institutes of Health (NS082432-03).
(Editor’s Note: What follows is an excerpt from an article that appeared in the June issue of Concussion Litigation Reporter. To see the full story, please subscribe at http://concussionpolicyandthelaw.com/subscribe/)
The family of high school lacrosse player Kendalle Holley has sued the School Board of Orange County (Fla.), the Florida High School Athletic Association (FHSAA), and an opposing Lacrosse player, after the opposing lacrosse player struck her in the head with a stick and caused a concussion.
The plaintiffs went on to claim that Holley, who plays for East River High School, was not properly evaluated, leading her to be reinserted in the game, causing a “severe exacerbation” of her injury, which they described as “continuing” and “permanent” …
(Subscribers can access the actual complaint in our document repository here: concussionpolicyandthelaw.com/concussion-litigation-reporter/concussion-litigation-reporter-documents. To subscribe, visit http://concussionpolicyandthelaw.com/subscribe/)
Virginia Tech is leading a $3.3 million, multicenter, five-year study that will track head impact exposure in children — the largest and most comprehensive biomedical study of youth football players to date.
Funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, researchers will track on-field head impacts and accelerations using sensors installed in hundreds of players’ helmets.
A new addition to the study will be mouth guards, which also will have sensors installed in them. Players at six schools in three states also will receive neuropsychological testing.
Leading the study is Stefan Duma, head of Virginia Tech’sDepartment of Biomedical Engineering and Mechanics, part of the College of Engineering.
Duma and his multi-university team will focus on six teams of 9- and 10-year-old players in three states, following each team during a five-year period, as well as the players themselves until they reach the age of 14.
“This is the largest coordinated youth study with the most advanced combination of instrumentation, clinical and neuropsychological testing,” said Duma, one of the earliest pioneers to study the biomechanics of football player head injuries and creator of a groundbreaking safety ratings system for football helmets and hockey helmets.
“Collecting this data during the next five years will allow for evidence-based decisions across a range of applications, including improved clinical detection techniques as well as a solid foundation for our helmet rating programs and offer ways potentially to improve youth football helmet design,” added Duma. “We will work with Pop Warner and other national governing bodies to develop improved practice strategies.”
Participants will be instrumented with two high-tech sensor systems, one located inside the helmet and the other in the front part of the player’s mouthpiece, each measuring all head impacts and rotations during all practices and games.
Data will be transmitted instantly to researchers near the sidelines, monitoring all impact levels. All practices and games will be videotaped to match sensor data with actual visuals of on-field impacts. Participants will undergo neurocognitive examinations off-field, involving computerized tests, balance scores of postural stability, and survey data.
“This study will provide important translational outcomes including an improved understanding of the rotational kinematics during football head impacts in the youth population,” said Steve Rowson, assistant professor of biomedical engineering at Virginia Tech, who has worked with Duma for the past 10 years. “This can lead to improved injury risk functions that could be used across all sports as well as automobile safety applications.”
Virginia Tech researchers will monitor and collect data from two local Blacksburg recreational teams. Long-time study collaborators Wake Forest School of Medicine, part of Wake Forest Baptist Medical Center in North Carolina, and Brown University in Rhode Island will each monitor and collect data from two youth football teams in their respective region.
The two teams at Wake Forest School of Medicine are lead by Joel Stitzel and Jill Urban, with additional funding from the Childress Institute for Pediatric Trauma. At Brown University, Trey Crisco and Beth Wilcox lead the research efforts for their two teams.
Also leading the research team are Jonathan Beckwith and Rick Greenwald, founder of New Hampshire-based technology firm Simbex and Art Maerlender of the University of Nebraska Lincoln, who will head neuropsychology testing and collection.
As with earlier studies involving scores of Virginia Tech athletes, this study also will involve Mike Goforth, head athletic trainer, and Brett Griesemer, assistant trainer, both with Virginia Tech Athletics; Gunnar Brolinson, professor of sports medicine and head team doctor, and Marc Rogers, an associate professor of sports medicine, both with the Edward Via College of Osteopathic Medicine; and Eric Smith of the Department of Statistics with the College of Science at Virginia Tech.
Virginia Tech biomedical engineering doctoral students working on the study are Megan Bland of State College, Pennsylvania; Eamon Campolettano of Hicksville, New York; Jaclyn Press of Doylestown, Pennsylvania; Jake Smith of Pittsburgh, Pennsylvania; and David Sproule of Houghton, Michigan.
“Five years from now, the hope is that we have a very strong understanding of the severity and frequency of impacts for youth football,” said Campolettano, who joined Duma and Rowson’s research team earlier this year. “Further, we can use this data to design improved testing methodologies for youth football helmets.”
Simbex is supporting the Head Impact Telemetry System – or HITS, for short – instrumentation that is part of the Elyria, Ohio-based Riddell’s Sideling Response System that records head impact exposure.
HITS is an accelerometer array mounted against a player’s head, inside the helmet, that will be used to quantify linear and rotational accelerations. The system builds on technology previously used to measure head impacts of Virginia Tech football players since 2003.
Instrumented mouth guards purchased from a second private firm, Kirkland, Washington-based I1 Biometrics will be custom fit to each player. Called the Vector, the mouth guard uses accelerometers and gyroscopes to measure linear and rotational accelerations. Both HITS and Vector transmit data wirelessly in real-time to researchers on the sidelines.
Coordinating statistical analysis for the study, Virginia Tech’s Eric Smith added, “It is quite natural for statisticians to be part of projects such as this one as statisticians are partly ‘data engineers.’ We think a lot about the data collection as a process and work to ensure the quality of the data.”
The grant is awarded using funds from the National Institutes of Health’s Bioengineering Research Partnership (BRP). This is the second BRP for this research team, and it expands on a previous award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The first BRP focused on collegiate football and hockey and resulted in more than 100 technical publications and presentations.
Duma and his research team have garnered international recognition during the past decade for creating a ratings system for adult football helmets, as well as a similar system for hockey helmets introduced this year.
Additionally, Duma is part of a $30 million national effort to combat concussions among college athletes and active military personnel.
The three-year project involves male and female NCAA student-athletes participating in football, women’s soccer, men’s soccer, and women’s lacrosse.
Virginia Tech’s Institute for Critical Technology and Applied Science provided support in developing the successful proposal submission to the National Institutes of Health, said Duma.