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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).
Using susceptibility-weighted imaging (SWI), researchers have identified microstructural changes in the brains of male and female college-level ice hockey players that could be due to concussive or subconcussive trauma. Until now, SWI has been used to detect signs of more severe cases of traumatic brain injury (TBI). This is the first time SWI has been used to detect signs of concussion (or mild TBI), and the first time it has been used to detect changes in the brain prospectively over an entire sports season in athletes of both sexes. The researchers, hailing from several institutions,1 describe and discuss their findings in “Hockey Concussion Education Project, Part 1. Susceptibility-weighted imaging study in male and female ice hockey players over a single season. Clinical article,” by Karl G. Helmer and colleagues, published in the Journal of Neurosurgery. Two additional papers from the Hockey Concussion Education Project (HCEP) on imaging techniques used to detect and follow concussion’s effects are also being published.
SWI is a high-resolution three-dimensional gradient-echo magnetic resonance imaging (MRI) technique that is particularly sensitive to the presence of blood and blood-breakdown products. SWI can be used to detect cerebral microbleeds, which are small hemorrhages that appear hypointense (contrasting to the appearance of other parts of the brain) on T2*-weighted magnetic resonance images. These microbleeds are often the result of traumatic brain injuries (TBIs). Until now SWI has been used to detect microbleeds larger than 5 millimeters—often a sign of severe TBI. In this study, Helmer and colleagues used SWI to detect clusters of much smaller cerebral microbleeds—ones that are too small to be seen with the naked eye but could represent acute and chronic injuries to the brain due to concussion or subconcussive events.
The authors report findings in college-level ice hockey players (25 men and 20 women) who initially agreed to participate in the study. These results document the innovative SWI analysis of the participating athletes prospectively during the hockey season, including pre- and post-season testing. Some of these athletes reported a history of concussion prior to the study period and some reported receiving no such injuries. During the season, 5 male and 6 female athletes sustained concussions that were identified and diagnosed by independent (study) medical specialists that attended each game. These athletes underwent additional SWI at 72 hours, 2 weeks, and 2 months after their injuries as well as serial clinical and neuropsychological evaluations. The researchers identified small clusters of hypointensity, which can be related to concussion (mild TBI), on SWIs obtained at time points in all participants. To compare the extent of these hypointense regions within and between individual athletes and groups of athletes, the researchers calculated a hypointensity burden (HIB) metric for each athlete at each SWI time point.
Helmer and colleagues report no significant change in the HIB value between the beginning and end of the hockey season in either male or female athletes who did not sustain a concussion. When the researchers compared HIB values in nonconcussed athletes according to sex, however, they did identify significant differences both at the beginning and end of the season, with male athletes having significantly higher mean HIB values than female athletes at both time points.
Among the athletes who did sustain a concussion during the season, the researchers report a statistically significant difference between the HIB value determined at the beginning of the season and that determined 2 weeks after concussive injury in male athletes and a similar—albeit not significant—difference in the HIB value during the same period in female athletes. These changes in HIB values point toward damage sustained at the time of impact as well and may indicate later effects of concussion. It is not unusual for a TBI to produce a two-pronged effect: immediate damage from the impact and secondary damage from injury-induced metabolic changes in the brain. In concussed athletes, the researchers also identified a difference in HIB values between the sexes, with male athletes having higher mean HIB values than female athletes at all SWI time points throughout the season.
The authors note that not all clusters of hypointensity seen on susceptibility-weighted images may represent small microbleeds; some may prove to be false-positive findings. However, given changes in the HIB metric following concussion, the researchers believe that SWI may be a useful diagnostic tool in detecting the effects of concussive impacts over time.
As to the differences in the HIB metric between the sexes, the researchers hypothesize various reasons why this occurred, including the possibility that the male athletes may have accumulated more extensive injuries from pre-study concussive and subconcussive impacts. Additional studies in a greater number of participants are called for, because these may lead to a clearer description of why the HIB metric differed between the sexes in this study.
In summarizing the value of SWI for detecting injuries due to concussion in athletes participating in contact sports, the researchers state: “Data acquired using this method could be used for the monitoring of players throughout their careers and could lead to improved diagnoses and return-to-play guidelines.”
When asked to comment on the importance of this study, Dr. Paul Echlin, senior co-author and primary HCEP investigator in this study, stated, “This study contributes to converging objective evidence concerning the acute and chronic effects of repetitive brain injury in the sports. Although future studies are warranted to further validate these initial findings (as well those found in the two accompanying HCEP studies), a cultural shift must be considered toward both the permitted violence that underlies many of the sport-related brain injuries and the high incidence of head impacts that occur in the games which our children play.”
Medical professionals around the world have escalated efforts to develop better treatment of traumatic brain injury (TBI) as concern grows over the serious consequences of head trauma and the increased damage that can result from repeated injuries.
TBI is caused by a blow or jolt to the head, or a penetrating head injury that disrupts the normal function of the brain. In the United States traumatic brain injuries contribute to deaths and cases of permanent disability. Every year, a significant number of TBIs occur either as an isolated injury or along with other injuries. Repeated traumatic brain injuries have a cumulative impact on brain pathology and neuropsychiatric health.
Recently, Carestream announced an agreement with the NFL Buffalo Bills football team to collaborate in gathering information for use in the development of new technology to diagnose and treat head injuries, including:
- Early diagnosis and accurate assessment of injured areas;
- Development of medical standards that indicate if an athlete can return to play; and
- Research that can assist in early diagnosis of long-term degenerative medical conditions in the head and brain.
Carestream’s work with the Bills will help ensure that the unique requirements for diagnosing and managing athletic injuries are included in our product design considerations. In addition, our collaboration with biomedical researchers from the world-renowned Johns Hopkins University can accelerate development efforts to deliver the best product for this critical area of medicine.
“Carestream and Johns Hopkins University are collaborating on the development of new 3D imaging systems, including a cone beam CT (CBCT) system that could provide unprecedented levels of image quality suitable to imaging of TBI. The collaboration involves the scanner design, development of imaging techniques and algorithms optimized for TBI imaging, and early clinical evaluation. Areas of application range from the hospital ICU to trauma, sports and the military theater,” said Jeffrey H. Siewerdsen, PhD, FAAPM, Professor, Department of Biomedical Engineering, Johns Hopkins University. “Recognizing the major health burden associated with TBI – much of which has only recently come to light – our hope is to develop a dedicated system for high-quality imaging of head trauma and brain injury in a form that is well suited to the point of care.”
Our goal is to expand the existing knowledge of traumatic brain injuries. The work ahead of us is challenging, but our R&D staff has the expertise to work with other research experts to develop new medical imaging systems that can help physicians diagnose and treat these debilitating injuries at the earliest stages.