Diffusion Tensor Imaging: A New Window Into Mild TBI

Andrew N. Wilner, MD; Christine MacDonald, PhD


June 18, 2012

Editor's Note:

Each year in the United States,traumatic brain injuries (TBIs) are responsible for 52,000 deaths and 1,365,000 emergency department visits. Research with new imaging modalities is providing new insight into the pathophysiology and extent of TBI. On behalf of Medscape, Andrew N. Wilner, MD, interviewed Christine MacDonald, PhD, Instructor in Neurology, Washington University School of Medicine in St. Louis, Missouri, at this year's American Academy of Neurology Annual Meeting on developments in the detection and management of TBI.

Dr. Wilner: During a symposium on TBI at the American Academy of Neurology 2012 Annual Meeting, we learned that in the United States, these injuries are responsible for 52,000 deaths, 275,000 hospitalizations, and 1,365,000 emergency department visits each year. In addition, many more patients probably have milder injuries but do not see a clinician or go to the emergency department. One of the problems for physicians is that when these patients with mild TBI are examined, often the neurologic examination and even the CT scan are normal, yet the patients complain of headache and dizziness, memory loss, and irritability.

Dr. MacDonald, your presentation focused on new methods of imaging TBI, particularly mild TBI.[1]Can you tell us more about that? How can more advanced neuroimaging help us with this clinical conundrum?

Dr. MacDonald: Absolutely. Our focus has been on the military population. However,we believe that new imaging methods could offer insight and elucidate some of these more mild injuries in the civilian population. We believe that one imaging method in particular, diffusion tensor imaging (DTI), will be especially sensitive to changes in the white matter of the brain. We think that is important because many of our efforts are focused on axonal injury, and better understanding the role of axonal injury in cognitive and psychiatric dysfunction after traumatic brain injury.

Dr. Wilner: Is DTI available with conventional MRI?

Dr. MacDonald: One of the strengths of this approach is that this technique can be applied readily with any standard clinical scanner; it usually requires about 4-6 minutes per picture. The challenge that we are currently still investigating is the analysis of these images; they are a quantitative image rather than an image that can be visually reviewed by the radiologist. We are taking measurements. Much of the focus now is on development of software and automated systems to quickly analyze the data and spit out results that will be clinically useful for the provider who is trying to better understand what is happening with the patient.

Dr. Wilner: Do you ever see abnormalities on DTI in an MRI that would otherwise have been read as normal?

Dr. MacDonald: Yes. In patients with very mild TBI, we have seen a large number of patients whose CT scans and conventional MRI images were negative, but we observed DTI abnormalities suggestive of injury.

Dr. Wilner: Because this is a quantitative measurement, is it possible and advantageous to look at these studies longitudinally and compare an image from today and then 1 year later?

Dr. MacDonald: That's a great question. We believe that is the case, and quite a bit of research is ongoing to try to validate that. Many studies have scanned patients during that early phase in the days to weeks after the injury, in the subacute phase (months after the injury), and then during the more chronic phase (years after the injury) to see whether there are changes that persist or even emerge later on in time. That progression of the signal characteristics over time is something that we think would be very useful in many contexts, be it civilian head injury, military head injury, or in the context of repeated head injuries and repeated exposures.

Dr. Wilner: You mentioned that you have been involved in research with the military. Do you have any ongoing studies that are not classified?

Dr. MacDonald: We have 2 Department of Defense studies that are ongoing. The principal investigator is David Brody; I am the director; and they are funded by the Department of Defense, specifically CDMRP (Congressionally Directed Medical Research Programs). One study in particular is expanding the initial cohort of active-duty military personnel and using new imaging methods, and the other is a radiologic/pathologic correlation study.

Dr. Wilner: I assume most of these are military personnel from Iraq and Afghanistan?

Dr. MacDonald: They all have been and continue to be specifically from Afghanistan. They are all individuals who were medically evacuated from those theaters of operation to Germany, which was the closest place to those folks in theater that had an MRI scanner.

Dr. Wilner: What do you hope to learn from these studies?

Dr. MacDonald: We hope to do a variety of things, but in particular we hope to gain some insight into whether or not the exposure to blast has a specific contribution, and whether particular abnormalities in the brain are associated with blast. We want to learn whether there are differences between blast-related TBI and TBI from other mechanisms. And we are looking at whether or not these different cohorts have particular outcomes, be they positive or negative, after these types of events. But first we need to confirm the feasibility of this approach, validate this imaging method, and verify and validate that we can do this.

We are one of many groups that are working with this. An incredible amount of credit goes to the willingness and support of the US military that has allowed for collaborations with academic institutions. This has been a huge step forward, to bring in academic experts to this population and work hand in hand to better serve these wounded warriors.

Dr. Wilner: Clinically, it can be very difficult to differentiate postconcussive syndrome symptoms from post-traumatic stress disorder symptoms. Patients may complain of exactly the same things -- problems with memory, irritability, and concentration; they have behavioral outbursts; and certainly an injury may have led to the PTSD. Will MRI with DTI become a tool that will help us separate these entities, or at the very least to learn more about them?

Dr. MacDonald: The jury is still out on that. We do not know definitively the answers to those questions, but we do hope to learn from these cohorts as we collect a multitude of information about their outcomes, in combination with these images.

Dr. Wilner: Dr. MacDonald, I want to thank you very much for spending a few minutes with Medscape to tell us about your research and how we are trying to learn more about TBI and in particular to help those service men and women who return to the United States with these injuries.


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