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  • Imaging Sheds New Light on Concussion Consequences

    June 01, 2014

    Sophisticated imaging techniques help identify and measure the risks associated with concussion.

    By Elizabeth Gardner

    From peewee soccer to the National Football League (NFL), concern about the long-term risks of sports-related head injuries continues to grow.

    Last summer, more than 4,500 retired NFL players, all suffering from chronic traumatic encephalopathy (CTE) and other chronic conditions related to concussion, sued the league alleging that it hadn’t done enough to protect them. The lawsuit elicited a proposed settlement of $765 million, which is pending court approval.

    To avert, or at least minimize, future injuries, researchers are using sophisticated imaging techniques to identify and measure the risks associated with such head trauma.

    At Stanford University, researcher and nueroradiologist Michael Zeineh, M.D. Ph.D., will conduct a series of advanced imaging studies on 40 football players—half the university’s team—along with a control group of volleyball players, over two years. In the project, “Multimodal MRI to Detect Brain Injury in Athletes,” funded through a 2013-15 ASNR/RSNA Research Scholar Grant, Dr. Zeineh and colleagues will work to pin down the elusive effects of repeated concussions and subconcussion-level head injuries. Dr. Zeineh hopes to supplement previous studies showing lasting brain changes from such mild traumatic brain injuries (TBIs).

    Researchers will use advanced diffusion tensor imaging (DTI) to image changes in microstructure, quantitative volumetric techniques to measure changes in brain structure and susceptibility-based imaging to quantify iron deposition—all findings that may be associated with CTE. Players will use special mouth guards during practices and games to measure head acceleration during impacts and keep a tally of the number of impacts. They will also have their blood tested for changes in inflammatory and neurodegenerative biomarkers.

    Conducting a longitudinal study is key, Dr. Zeineh said. “With no baseline pre-trauma imaging, these patients are usually compared to a control group to identify differences indicative of brain injury,” he said. “Unfortunately, findings are obscured by the extensive variability in brain morphology.”

    “Heading” a Soccer Ball Linked to Brain Injury

    Though there’s growing evidence that repeated concussions and subconcussion-level head injuries—typical in sports like football and soccer—can leave lasting effects on the brain, that evidence raises many more questions: Who’s most likely to be affected? What does the damage look like? How many impacts are too many? And what’s the best way to safeguard the brain health of athletes?

    Michael L. Lipton, M.D., Ph.D., gave a jolt to the soccer community with his RSNA 2011 research on the practice of “heading,” a fundamental soccer technique using the head to return or redirect the ball—demonstrating that heading was associated with changes in brain structure and function similar to those of mild TBI. The research was also published in the September 2013 issue of Radiology.

    Dr. Lipton, associate director of the Gruss Magnetic Resonance Research Center at the Albert Einstein College of Medicine and medical director of MR imaging at Montefiore Medical Center in New York City, and colleagues used DTI to study 37 amateur soccer players (average age: 30.9 years), all of whom have played the sport since childhood. DTI produces a measurement, called fractional anisotropy (FA), of the movement of water molecules within and along axons, which make up the bundles of nerves in the brain’s white matter.

    They then compared the brain images of the most frequent headers with those of the remaining players and identified areas of the brain where FA values differed significantly.

    “Between the two groups, there were significant differences in FA in three brain regions in the temporooccipital region,” Dr. Lipton said. “Soccer players who headed most frequently had significantly lower FA in these brain regions.”

    The regions identified by the researchers are responsible for visuospatial attention, memory, multisensory integration and higher-order visual functions.

    The paper elicited contrary reactions, Dr. Lipton said. “Some people were concerned, but at the same time asked, ‘Isn’t this all very obvious and intuitive?’ Others were dismissive and said, ‘What’s the big deal? We’ve been doing this for a long time.’”

    Threshold Effect Key to Research

    Dr. Lipton said the paper’s key finding is the evidence of a threshold effect. “It wasn’t linear,” he said. “Players with fewer than 800 headers over the prior 12 months didn’t have elevated risk for either brain changes or cognitive effects. There’s likely to be some amount that’s not good for anyone, but there’s also a range that seems to be well tolerated.”

    Dr. Lipton is now beginning a longitudinal study funded by the National Institutes of Health and the Dana Foundation examining several hundred amateur adult soccer players over several years. Researchers will measure how both the appearance and function of their brains change over time in proportion to the amount of heading and other head injuries they sustain. “The major limitation of current studies is that you can’t make any explicit inference about causation,” Dr. Lipton said. “We’re looking at one point in time and seeing an association, but there’s no proof that heading is the cause. Looking longitudinally, we can make that determination.”

    Both DTI and susceptibility-weighted imaging involve post-processing image analysis, which can reveal subtle forms of injury that may not be evident during a visual examination of the image. “It is important to recognize that relatively minor impacts can have non-minor consequences,” Dr. Lipton said. “Using standard best-practice clinical protocols and high-quality CT or MR, a person with a brain injury may look normal, but that doesn’t mean the brain is normal. Quantitative techniques can detect very subtle, maybe subclinical, signs of brain injury. It’s going to be a big part of the future in diagnostic imaging.”

    Another question researchers are tackling is, “How do we determine when a player can return to the game after a head injury?” said Yvonne W. Lui M.D., neuroradiology section chief at Langone Medical Center at New York University. Dr. Lui’s June 2013 Radiology research on brain volume changes associated with mild TBI found measurable brain atrophy a year later in 32 patients who had only one concussion. “It’s hard to know with biomarkers whether someone has fully recovered.”

    Dr. Lui said anywhere from 15 to 30 percent of patients will have prolonged symptoms after a concussion. Figuring out who they are beforehand—through genetic factors or other biomarkers—will help steer the most vulnerable away from sports and activities that carry a high risk of head impacts.q

    Web Extras

    • Access the September 2013 Radiology article, “Soccer Heading is Associated with White Matter Microstructural and Cognitive Abnormalities,” by Michael L. Lipton, M.D., Ph.D., and colleagues, at Pubs.rsna.org/doi/full/10.1148/radiol.13130545.
    • Click Supplemental Materials in the article above to hear Dr. Lipton discuss his Radiology research in a podcast.
    • Access the June 2013 Radiology article, “Mild Traumatic Brain Injury: Longitudinal Regional Brain Volume Changes,” by Yvonne W. Lui, M.D., and colleagues at Pubs.rsna.org/doi/full/10.1148/radiol.13122542.

    Elizabeth Gardner is a writer based in Chicago specializing in medical technology and health IT issues. 

    Lipton soccer heading - three ROIs
    (Click to enlarge) Michael L. Lipton, M.D., Ph.D., gave a jolt to the soccer community with his RSNA 2011 research showing that soccer “heading” was associated with changes in the brain structure and function similar to those of mild traumatic brain injury. Above: Three ROIs in the temporo-occipital white matter detected by the initial voxelwise linear regression of estimated prior 12 months of heading on FA, shown as color regions rendered in 3D images and superimposed on T1-weighted axial (left), coronal (middle), and sagittal (right) images from the Montreal Neurological Institute template.
    Lipton soccer heading - FA at each ROI
    (Click to enlarge) FA at each ROI was significantly lower as a function of greater heading exposure. R = right. (Radiology 2013: 268;3;850-857) ©RSNA, 2013. All rights reserved. Printed with permission.
    Michael L. Lipton, M.D., Ph.D.
    Michael Zeineh, M.D. Ph.D.
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