Turning Up the Volume on a Silent Epidemic: Advanced Imaging & TBI

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 - TBI: Athlete with iPad
Source: University of Notre Dame

Through the 17 weeks of the National Football League 2012 regular season and four weeks of playoffs, there were 170 reported concussions, according to a collaborative effort to track the injuries conducted by PBS’ Frontline and ESPN. Attention to head injuries in sports has spiked—indeed, such a comprehensive list of NFL concussions would have appeared nowhere in the mainstream media five years ago. The sea change is due in part to increasing reports of long-term repercussions from the injury in athletes and military veterans, but also because medical imaging is revealing more about this previously silent epidemic.

Concussions, or mild traumatic brain injuries (mTBI), differ from severe TBI based on severity—mTBI results in brief changes in mental state or consciousness, while severe TBI can lead to extended periods of unconsciousness and amnesia. Despite the distinction in initial severity, more evidence is indicating that long-term cognitive deficits can be experienced even with mTBI. Each year, there are at least 1.7 million TBIs in the U.S., with concussions making up about 75 percent, according to the Centers for Disease Control and Prevention.

At the launch of the Concussion Center at NYU Langone Medical Center in New York City in March, Steven L. Galetta, MD, chair of the department of neurology at NYU Langone Medical Center, explained that only 15 percent of people who suffer concussions actually seek treatment. There has been a doubling of the concussion rate over the last decade due to increased recognition of the condition, but more research is needed.

Take one tablet & call me in the morning

While imaging is playing in a huge role in the study of mTBI, researchers at the University of Notre Dame in South Bend, Ind., are working on an imaging-free method of identifying concussions in athletes using a tablet-based testing system.

The system works by having athletes speak into an iPad tablet to establish a baseline reading of a person before a potentially concussion-inducing sporting event. A second sample is taken after the event, and the system looks for traumatic brain injury indicators, such as distorted vowels, hyper nasality and imprecise consonants.

Nine concussions were confirmed out of 125 student participants in a 2012 campus boxing tournament using the technique, according to a Notre Dame press release. Another set of tests conducted during the 2013 boxing tournament is currently being evaluated.

“We need better biomarkers, better imaging predictors of who’s at greater risk,” says Galetta. In the past, a person who hit his or her head or an athlete who had his or her “bell rung” might have been given smelling salts and then sent on his or her way, but Galetta says we are in the beginning stages of a major shift in how concussion will be approached in the future, with advanced imaging playing a key role in the process.

Shifting opinions

The tipping point in this change of attitudes actually came before concussions in sports were thrust into the spotlight. Soldiers returning from Afghanistan and Iraq were exhibiting signs of neurological deficits, despite normal brain appearance on CT imaging, leading to a desire to learn more about the characteristics of brain injury, says Rao P. Gullapalli, PhD, of the University of Maryland School of Medicine in Baltimore.

“I think public awareness has increased and, unfortunately, it had to be the wars and these football players, because this problem has been there all along,” says Gullapalli. “It just did not get attention because people lived with these symptoms.”

While soldiers and athletes brought the issue to the popular media, within the field of neuroradiology, advanced MRI techniques like diffusion tensor imaging (DTI) showed brain injuries could exist even when conventional imaging showed nothing wrong structurally.

“[DTI] sort of opened our eyes to say ‘Oh my goodness, there is something going on in here indeed and this was probably the cause of their long-term outcomes,’” says Gullapalli. No two concussions are the same, he adds, but research into the subtle changes connected to post-concussive symptoms has demonstrated the importance of looking at the midbrain and thalamus. Nerve fibers project out to the cortex from the thalamus and any disruption on the cortex can translate to communication breakdowns within these fibers.

The ability to analyze function as opposed to just structure is key to understanding brain injuries, according to Richard D. Bucholz, MD, of Saint Louis University in Mo. “[CT] is like looking at St. Louis from 20,000 feet,” he says. “You can make out the highways, the rivers and that sort of thing … you can’t talk about what the people are doing and what communication is occurring within St. Louis, and therein lies the utility of MRI and magnetoencephalography.”

Bucholz and colleagues have teamed up the Department of Defense to study TBI of varying degrees among members of the military. The fact that soldiers subjected to blasts from improvised explosive devices suffer prolonged neurological deficits despite unremarkable CT results presents an opportunity to investigate the use of advanced MR and other techniques.

“Coming up with a noninvasive way of imaging that patient will be extremely useful, and MRI and magnetoencephalography really fits that bill,” says Bucholz. “Rather than simply confine ourselves to the structure of the brain … we should confine ourselves to the connectivity occurring within that brain during that period of time.”

Likewise, Gullapalli touts the benefits of research combining multiparametric MRI, brain perfusion analysis and a study of biochemical changes.

Imaging here and now

Current imaging research into mTBI is providing fascinating insight, but it has not yet translated into many changes in how imaging is used in clinical practice. In fact, imaging is not needed in typical concussion cases unless symptoms worsen, according to Galetta. “Most symptoms of concussion are going to clear within seven days and if somebody is progressing in the right direction, the role of diagnostic imaging could be questioned.”

But symptoms will worsen in some patients. About one in six people who suffer a concussion develop persistent post-concussive symptoms, says Esther L. Yuh, MD, PhD, of the University of California, San Francisco. This “miserable minority” suffers from headaches, mood problems, depression and sleep issues long after their injuries.

Advanced techniques may lead to biomarkers that identify those most susceptible to prolonged suffering, but Yuh and colleagues wanted to see what conventional imaging factors could help predict outcomes when combined with clinical factors. “We wanted to go back to the ground level and see what could be done at all hospitals to try to predict how people do,” she says.

The researchers designed a prospective study to assess the relevance of early CT and MRI, and analyzed imaging from 135 patients who presented with head injuries at the emergency departments of three Level 1 trauma centers. Outcomes at three months were measured.

What they found was that imaging findings—even conventional imaging available at most facilities—do add predictive power, with MRI identifying more acute traumatic intracranial lesions than CT. Yuh and colleagues devised multivariate models to predict outcomes, with the most comprehensive model incorporating clinical, demographic and socioeconomic factors with CT and MRI features.

The work represents progress in the evidence-based classification in brain injury severity, but cost-effectiveness represents a major issue. Since the majority of mTBI patients recover well, conducting routine MRI is currently not likely to be a favorable option, says Yuh.

That may soon change, however, if advances in MRI technology make the modality more accessible. Yuh says vendors are currently working on a miniature MR scanner to provide localized imaging of the head. With a helmet-like shape, such a scanner could be installed in emergency departments to make MR scans of concussion patients more practical. Gullapalli says a sensitive and local MRI of this type would revolutionize the diagnosis of head injuries.

In the meantime, concussions will continue to be taken more seriously by physicians, coaches and training staffs around the country. More dedicated multidisciplinary concussion centers are opening, including Methodist Concussion Center in Houston and Cleveland Clinic Concussion Center, and the NFL is refining its concussion protocols. The league’s general counsel expects independent neurologists, in addition to team physicians, to be available on the sidelines next season. The concussion epidemic is silent no more.

Sorting out alphabet soup: CTE vs. TBI
Pathology by MRI compared to CT. (A–C) 50-year-old man. (A) Normal head CT. MRI at 7 days showed (B) hemorrhagic axonal injury along right lateral ventricle (yellow arrow) and (C) right frontal contusion (red arrows). (D–H) 19-year-old woman. (D) Head CT showed no intracranial hemorrhage. (E) MRI at 12 days showed hemorrhagic axonal injury in deep right frontal white matter (yellow arrow) and (F–H) 4 unsuspected hemorrhagic contusions (red arrows). (I–M) 54-year-old man. (I) CT interpreted as trace right frontal subarachnoid hemorrhage (red arrow). (J–M) MRI showed numerous discrete foci of subcortical white matter signal loss (yellow arrows).
Source: AnnNeuro 2013;73:224-235

Although chronic traumatic encephalopathy (CTE) may be confused with TBI, it represents a distinct condition. CTE is a progressive degenerative disease that results from a series of low-level injuries, rather than a single blow to the head.

Those with CTE exhibit signs of brain tissue degeneration and an accumulation of tau proteins, resulting in dementia-like symptoms, including memory loss, depression and confusion.

One of the tragic elements of CTE is that it currently can only be diagnosed through autopsy. A total of 33 former NFL players have been posthumously diagnosed with CTE, including Ray Easterling and Junior Seau, who both committed suicide in 2012.

One of the issues in researching CTE is a lack of a long-term, serial imaging data on individuals, though the increased attention has spurred more trials to research how imaging can help identify CTE earlier, and hopefully improve treatment.