Researchers have shown that three novel imaging techniques can detect mild brain damage not visible using traditional methods. The findings will help scientists better define the type of damage that can lead to long-lasting memory and emotional problems, as well as help identify those who are most vulnerable to further trauma.

Such tools are of great interest to the military, which needs ways to distinguish traumatic brain injury from post-traumatic stress disorder. Both are common in veterans returning from Iraq and Afghanistan, and they have similar symptoms, but they require different types of treatment. The new imaging methods may also shed light on the effect of repeated mild brain trauma, such as concussion, for which soldiers and professional athletes are at risk. Anecdotal reports about ex-football players who developed early dementia, as well as concern for thousands of military troops exposed to repeated explosions, have made the long-term consequences of these types of injury an important and controversial issue.

“Right now, a football coach has no way of knowing who can go back on the field and who shouldn’t, a military officer doesn’t know who should be removed from the battlefield, a lawyer doesn’t know who has a real injury and who is faking,” says David Brody, a neurologist and scientist at Washington University, in St. Louis.

Mild traumatic brain injury is notoriously difficult to diagnose. The brains of concussion patients often look normal on CT scans, the most common test after head trauma, and “cognitive deficits can be subtle, even to a neurologist,” says Michael Selzer, a neuroscientist at the University of Pennsylvania. Fortunately, most people with concussions recover within days or weeks. But about 10 to 15 percent have persistent problems, including headaches, nausea, memory deficits, and emotional abnormalities that can linger for months or years.

Scientists hypothesize that mild head trauma damages the brain’s white matter–the long projections, called axons, that ferry messages between neurons. White matter is invisible to CT scans and magnetic resonance imaging (MRI). One of the most promising techniques for detecting subtle brain injury, called diffusion tensor imaging (DTI), is a variation of MRI that tracks water molecules in the brain’s white matter. In research presented this week at the Society for Neurosciences conference in Washington, DC, Brody and his colleagues found that DTI analysis of brain-injury patients revealed signs of white-matter damage not visible with normal MRI. The damage seemed to correlate with cognitive deficits, including slowed reaction time.

A second variation of MRI, known as magnetic resonance spectroscopic imaging (MRSI), can analyze the spectral frequencies of chemicals in the body. Andrew Maudsley and his colleagues at the University of Miami have used new advances in MRI technology, including higher-power magnets, to develop MRSI methods that can measure concentrations of two chemicals in the brain: n-acetylaspartate (NAA), a marker of white-matter density, and choline, which has been linked to injury. Previous MRSI methods yielded information only about specific brain regions, but the new technique can measure chemical concentrations across the whole brain. The researchers found decreases in NAA, possibly due to damaged axons, and increases in choline in a group of 25 patients with traumatic brain injury. “We see widespread metabolic changes, even in those with the mildest injuries,” says Maudsley, who presented the work at the conference.

A third study presented at the conference found that changes to slow-wave activity, which have been previously linked to traumatic brain injury, are likely caused by damage to the white matter. Mingxiong Huang and his colleagues used magnetoencephalography (MEG), which measures the magnetic fields produced by the electrical activity of nerve cells, to pinpoint the source of abnormal brain activity, and they discovered that it often overlapped with the location of damage detected using DTI.

While the research is promising, moving these new technologies into clinical use is likely to be a challenge. “The bar for clinical diagnosis of individual patients is different than for measuring a group effect,” says David Moore, a neurologist at Walter Reed Army Medical Center. Physicians would need to be able to detect brain changes characteristic of injury on an individual level.

Both DTI and MRSI can be performed using most standard MRI machines, but they require much more extensive data analysis than most medical imaging, something that radiologists aren’t used to providing. “It is computationally and analytically intensive,” says Brody. MEG, which is used to pinpoint seizures in epilepsy patients, is even more complicated, and the machines are still quite rare in clinical centers.

In addition, it’s not yet clear how soon after injury these approaches can identify patients likely to suffer long-term problems. While no protective treatments for brain injury yet exist, they are under development, and they would need to be delivered immediately.