Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) are presenting new health care challenges. Ninety percent of soldiers wounded in Iraq survive their injuries. In many cases, these war-related injuries are complicated. Many soldiers with polytrauma suffer brain injury. In one survey, 61 of 88 blast injuries treated at Walter Reed Army Hospital included traumatic brain injury (TBI). It is estimated that soldiers deployed for 18 months will experience an average of 10-12 blast exposures during the course of their tours in Iraq. The potential longer-term complications of these repeated blast exposures not resulting in evacuation are not well understood. The possibility that these soldiers may have incurred milder forms of undetected brain injury has not been well investigated. Although detection of severe TBI is relatively easy, the detection of mild to moderate injury poses challenges, and no clear objective imaging markers exist to follow or guide the patient's recovery during the course of therapy. This is compounded by the fact that it is difficult to obtain magnetic resonance (MR) images of soldiers immediately following blast injury in the field.

Although not perfect, the closest we can get to a scenario of blast injury is in the case of motor vehicle accident that involves diffuse axonal injury (DAI). Computed tomography (CT) is usually the scan of choice upon presentation, as it is convenient, quick, and provides a good measure of clinical assessment, which leads to appropriate therapeutic remedy such as removal of extra-axial hemorrhage. However, patients with poor clinical presentation but without any abnormality on CT pose a diagnostic and therapeutic challenge. Conventional MRI is more sensitive than CT scanning in the detection of DAI as it can detect punctuate deep white matter hemorrhages, considered a hallmark of DAI. However, even conventional MR may be unable to visualize microscopic injury such as hemosiderin laden macrophages and lymphocytes in the white matter. Both conventional MR and CT are known to underestimate the extent of DAI injury and have correlated poorly with the final outcome. It is believed that TBI results in a combination of cytotoxic injury and extracellular vasogenic edema in the early stages, which is followed by increased extracellular fluid, ultimately resulting in cerebral atrophy or encephalomalacia. Novel MR imaging techniques such as diffusion tensor imaging (DTI), magnetic resonance spectroscopic imaging (MRSI), and susceptibility-weighted imaging (SWI) are sensitive to such changes and potentially can detect early changes. Parameters derived from these techniques provide an insight into the biophysical, biochemical, and vascular changes in various regions of the brain.

In this 3-year project, we propose to study the sequelae of TBI on patients admitted to our Shock Trauma center by imaging them immediately after admittance and then longitudinally follow them over the course 18 months. Specifically, we would like to test the efficacy of novel MRI techniques developed in the last few years that provide information on biophysical, biochemical, and vascular alterations using DTI, MRSI, and SWI. Our study is focused on monitoring early changes using the above techniques and following these changes over 18 months. This project is expected to answer the following questions:

a. Are novel imaging markers able to reliably identify the nature and extent of injury compared to existing methods?

b. Which region of the brain and which technique or combination of techniques best describes the clinical condition of the patient?

c. Which regions of the brain are more predictive of the final outcome to the patients?

Forty patients each classified as mild, moderate, and severely injured based on the admission Glasgow Coma Scale will be recruited into this study. Imaging studies will be conducted upon admission (after the patient has been stabilized) and at 4 weeks, 6 months, and 18 months following injury to obtain early and late change information. Comparisons will be made between the injury groups and also with normal controls controlled for age differences.

A systematic assessment of these new techniques that provide information on biophysical, biochemical, and vascular changes has never been investigated in the Trauma environment. Results obtained from this study are expected to provide a more complete understanding of the sequelae of TBI that can be directly translated to an accurate assessment of TBI among war veterans of Operation Iraqi Freedom and Operation Enduring Freedom. Imaging markers that are sensitive to changes and have the ability to provide prognosis can be used to optimize therapeutic regimens for the patient and help in the development of novel therapies.