David L. Brody, M.D., Ph.D.; Washington University, St. Louis; Traumatic Brain Injury New Investigator Award

We're interested in better understanding of blast-related traumatic brain injury. Specifically we take the hypothesis that blast-related traumatic brain injury causes injury to axons in the brain. Axons are the wires that connect brain nerve cells from one part of the brain to another part of the brain. Without axons, parts of the brain cannot communicate effectively with each other and the brain is disabled.

There has been substantial animal research that suggests axons are the most vulnerable part of the brain to mechanical injuries. However, axonal injury is very difficult to assess in living patients. Conventional MRI scans and CT scans that are used in clinical practice are not sensitive to axonal injury.

Before we started on this project, we demonstrated in an animal model that a new type of MRI scan called Diffusion Tensor Imaging can detect axonal injury when conventional scans do not detect it. And in the animal model we had the advantage of being able to look at the animal's brain under a microscope so we could verify that this method, Diffusion Tensor Imaging accurately and quantitatively detects axonal injury.

So for this project sponsored by the CDMRP, we wanted to use this new method, Diffusion Tensor Imaging to assess the brains of soldiers who had suffered blast-related traumatic brain injury and were very much alive and functional but had various deficits afterwards to test the hypothesis that traumatic axonal injury is primarily responsible or one of the contributors to the deficits that are seen after traumatic brain injury.

We've recruited a total of 84 subjects from Landstuhl Regional Medical Center in Germany, and we've performed these Diffusion Tensor Imaging scans and conventional MRI scans as well on those 84 subjects. We've now seen 65 of these subjects back for a clinical follow-up six to 12 months after their initial injury here in St. Louis. At follow-up, we've scanned them again using the same method and performed a variety of cognitive tests and psychological assessments and psychiatric evaluations for post traumatic stress disorder and depression.

Our primary results thus far of our research have been in three main areas. The first result is that there have been substantial numbers of abnormalities on Diffusion Tensor Imaging that are consistent with traumatic axonal injury which were not apparent on conventional MRI. So our basic hypothesis appears to be true. And our claim that Diffusion Tensor Imaging is more sensitive than conventional MRI for this purpose also appears to be true.

The second main result is that the brain appears to have areas that are specifically vulnerable to blast-related injury that are different than the areas that are vulnerable to civilian traumatic brain injury. Computer simulations of the effects of blasts on the brain, specifically predicted that the highest mechanical forces would occur in the front, just above the eyes, and in the back part of the brain, the very low back part of the brain.

Those regions are not commonly injured in civilian traumatic brain injury. So our findings indicate that there are Diffusion Tensor Imaging signal abnormalities consistent with traumatic axonal injury in those orbital frontal tracks and in those posterior fossa tracks in these blast-related subjects, which are uncommonly abnormal in the setting of civilian injury.

The third portion of our major results which may be the most controversial is we found that injury as assessed using Diffusion Tensor Imaging helps us predict the severity of post traumatic stress disorder. Subjects with blast-related traumatic brain injury have a higher incidence of post traumatic stress disorder than subjects who have gone through the same sort of combat experiences but have not had traumatic brain injury.

Clearly further work is necessary to confirm this, but this method if successful will change medical care because it'll improve triage and early diagnosis for traumatic brain injury. If you can make a diagnosis earlier you can start interventions earlier and you can get better outcomes. So our hope is to be able to make earlier diagnoses and earlier interventions which will improve outcomes for soldiers with blast-related traumatic brain injury.