ARTICLE IN BRIEF
Investigators reported that diffusion tensor imaging can detect axonal injury in mTBI, which could assist in offering a more accurate prognosis.
A patient with mild traumatic brain injury (mTBI) can pose a challenge for the neurologist — the clinical symptoms may suggest tissue damage within the brain, but CT and MRI are usually normal. Now, a new study shows that diffusion tensor imaging (DTI) can detect axonal injury in mTBI. The study, published in the September issue of Radiology, also indicates that prefrontal damage is correlated with impairment of executive function shortly after the injury.
“The neurologist may have a lot of clinical information about the consequences of an injury, but usually there is no way to tell whether the brain has been structurally damaged,” according to lead author Michael Lipton, MD, PhD, associate director of the Gruss Magnetic Resonance Research Center and director of radiology research in the departments of radiology, psychiatry, and behavioral sciences and neuroscience at Albert Einstein College of Medicine in New York. “The open question, which we are trying to address in this study, is whether there is something wrong with the brain.”
DTI, he explained, is an application of MRI that is sensitive to the direction of movement of water molecules through tissue. In the intact brain, the primary direction of movement is parallel to axonal bundles, a condition called “anisotropy.” But when those axons are damaged, the movement becomes less aligned with the bundles.
“If there is a change in the direction of diffusion of water due to microscopic damage, it is reflected in a decrease in anisotropy,” he said.
Dr. Lipton and his colleagues performed DTI on 20 patients with diagnosed mTBI within two weeks of injury, along with 20 matched controls. Patients came to emergency rooms after either a motor vehicle accident or a fall, and met standard criteria for mTBI: a Glasgow Coma Scale score of 13 to 15, loss of consciousness not exceeding 20 minutes, and amnesia not exceeding 24 hours. No patient had gross brain abnormality as a result of injury, including microhemorrhages.
The patients exhibited classic signs of executive function impairment, including worse performance than controls on two tests of cognitive function. The patients also had significantly higher levels of depression, stress, and anxiety than control subjects.
DTI imaging revealed 15 clusters of lower fractional anisotropy in the white matter of patients compared to controls, five of which were in the frontal lobes. Based on the data, Dr. Lipton concluded that “lower fractional anisotropy is associated with poorer cognitive performance.” The region most implicated in this association was the dorsolateral prefrontal cortex, a key center for executive function, he noted.
“Our findings underscore the fact that real brain injury occurs after mild trauma, and that is accompanied by brain dysfunction,” he said. Detection of this damage using DTI represents a “major advance in diagnostic imaging.”
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It is not clear how to use the information that DTI can provide, but long-term follow-up studies may change that. The current study is just a snapshot of injury in the immediate post-injury phase, Dr. Lipton pointed out. Most patients with mild traumatic brain injury get better over weeks or months, so the next important question is whether cognitive improvement is accompanied by structural repair. If so, then DTI could be used as a biomarker in interventional studies, which currently suffer from lack of robust outcome measures.
If the correlation between structural and cognitive improvements holds up, and interventions can be developed to aid recovery, DTI might be a way to triage patients for different types of treatment, Dr. Lipton said.
“It could be easily incorporated into a standard MRI exam,” he said, taking perhaps an extra five minutes in the scanner. What most centers may not have is the ability to analyze the data, which requires special software and the training to apply it. But with time and resources, he suggested, this should not be a significant hurdle for more widespread adoption.
“This is a very interesting finding,” said Douglas Katz, MD, medical director of brain injury programs at Braintree Rehabilitation Hospital in Massachusetts, and associate professor of neurology at Boston University School of Medicine. “DTI is showing great potential for giving us more information about diffuse axonal injury, one of the typical types of brain injury associated with TBI. The difficulty in the past has been having some objective measure of diffuse injury, and it seems that DTI comes closest to being the best for that.”
“It is important to do imaging on these patients,” he said. “The only way to gauge severity in patients has been clinical recovery, or later, to measure brain atrophy, as a gauge of severity. The problem with both is that they can be affected by other things, including other pathologies, or the aging process.” DTI, he said, may offer a way to obtain more time-sensitive and therefore more valuable information on the patient's state.
“The other important thing in patients with mild TBI is to be able to diagnose whether there has been brain injury at all,” and whether that injury may be contributing to the patient's symptoms. Pain and depression can also contribute to the clinical picture, and these may be difficult to tease out. Imaging, he said, may offer a way to isolate the effects of brain injury itself.
“I think it is practical to think of DTI becoming a clinical tool. It will take more work to make it so — we're not there yet, but it has great potential to be a clinical tool for documenting axonal injury. Proper diagnosis can help direct treatment more appropriately, can help avoid mistreatments, and can help provide a more accurate prognosis,” Dr. Katz said.
• Lipton ML, Gulko E, Zimmerman ME, et al. Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild traumatic brain injury. Radiology 2009;252(3):816–824.