Radiological-Pathological Correlations Following Blast-Related Traumatic Brain Injury in the Whole Human Brain Using ex Vivo Diffusion Tensor Imaging

Thousands of US military personnel have had blast-related injuries to the brain due to the wars in Iraq and Afghanistan. Very large numbers of civilians also have traumatic brain injuries caused by car accidents, falls, sports-related injuries, or assault every year. We are not very accurate at detecting traumatic brain injuries right now, but there is a new type of MRI (magnetic resonance imaging) scan that we think will be able to show what has happened to the brain after trauma more clearly than regular scans can. This new scan is called diffusion tensor imaging. We believe that this will be able to show injury to the axons. The axons are the wiring of the brain. Under the microscope we can see that axons are frequently injured after traumatic brain injury, but regular MRI scans can't detect injured axons very well. This new type of MRI scan doesn't require any new machines, just a different way to use them. In our previous studies on animals, diffusion tensor imaging detected injured axons very well.

What Are the Goals of the Proposed Study? The goal of this study is to find out for sure whether diffusion tensor imaging can show injury to axons in the human brain. To do this, we will study brains from people who have died after traumatic brain injury. Some will be US military personnel who died from blast-related injuries. Some will be civilians with other types of brain injuries. First, we will scan these brains using diffusion tensor imaging. Then, we will look at slices from the brains under the microscope and count the number of injured axons. Finally, we will compare the diffusion tensor imaging scans side by side with the injured axon counts. We predict that the signals on diffusion tensor imaging will be most abnormal in areas with high injured axon counts, moderately abnormal in areas with lower injured axon counts, and normal in areas without injured axons. If this is true, we will then use diffusion tensor imaging to map the parts of the brain that most commonly have injured axons. We will also directly compare blast-related injuries with other types of injuries.

What Types of Patients Will It Help? If successful, this study will help military traumatic brain injury patients who have been injured by blasts. It will also help young adult civilian traumatic brain injury patients injured by car accidents, falls, sports-related injuries or assault. It could help younger and older TBI patients as well.

How Will It Help Them? This study will help them by demonstrating that diffusion tensor imaging is an accurate method for detecting injured axons. If it proves accurate, diffusion tensor imaging could help determine who has traumatic brain injury affecting their axons, how severe the injury is, and what parts of the brain are affected. This, in turn, could help with return-to-duty, return-to-work, and return-to-play decisions; guide rehabilitation; and allow patients and family members to know what to expect after brain injury. It may also help distinguish between traumatic brain injury and other causes of symptoms such as depression and post-traumatic stress disorder (PTSD); we expect to see injured axons after physical injury to the brain, but not in depression or PTSD. Furthermore, it could help identify people who are good candidates for experimental treatments designed to protect or repair injured axons. Finally, the information will help designers of helmets and other protective devices build better equipment to protect military personnel and civilians from brain injury.

What Are the Potential Clinical Applications, Benefits, and Risks? The potential clinical applications could include help with return-to-duty, return-to-work, and return-to-play decisions at early times after injury, distinguishing traumatic brain injury from other conditions, and guiding rehabilitation after a diagnosis of traumatic brain injury has been made. The benefits include improved accuracy in making all of these decisions. The risks are similar to regular MRI scans, which are considered very safe.

What Is the Projected Time It May Take to Achieve a Patient-Related Outcome? We estimate that it will require 3 years to complete this project and 2 more years after that before diffusion tensor imaging will become a commonly used clinical test. It will likely require 2-4 more years to design better protective equipment. We estimate that it will take 5-15 years to develop effective treatments designed to protect or repair injured axons.

What Are the Likely Contributions of This Study? This study, if successful, will likely give us a great deal of confidence that diffusion tensor imaging is an accurate method for determining whether axons have been injured. If it is accurate, this method will allow us to find out how common injury to axons is in patients who survive traumatic brain injury. Information about the regions injured most commonly will help designers of helmets and other protec .......