Of the nearly 1.4 million victims in the United States who receive medical treatment for traumatic brain injury (TBI) annually, 79% (1.1 million) sustain mild TBI (MTBI) resulting financial and functional problems that impact the healthcare system and society in general. Although prospective, longitudinal studies of unselected samples with comparison groups have shown that cognitive deficits and post-concussive syndrome (PCS) symptoms in MTBI patients generally resolve within 3 months, these symptoms persist in up to 20% of patients. Changes detectable on advanced neuroimaging techniques such as Diffusion Tensor Imaging (DTI) including increased fractional anisotropy (FA) and decreased apparent diffusion coefficient (ADC) have been reported in MTBI patients imaged within the first week post-injury and are attributed to a subtle form of cytotoxic edema. In contrast, DTI performed in the more chronic interval consistently shows decreased FA and increased diffusivity thought to reflect later degenerative axonal changes. However, little is known about the extent, duration and timing of these initial changes. Additionally, the relation between the degree of initial change in DTI parameters and long-term imaging parameters, cognitive sequelae, and PCS symptom persistence has not been systematically studied. The proposed project would build on our group's current NIH-funded program project """"""""Mild Traumatic Brain Injury and Diffuse Axonal Injury"""""""" (NIH/NINDS, P01 NS056202), which involves assessment of MTBI and moderate TBI (ModTBI) and includes parallel imaging studies of humans and a porcine model. The proposed study would involve recruitment of a subset of 20 patients from the PPG to perform a more detailed investigation of the acute DTI- and magnetization transfer imaging (MTI)-related changes occurring as a result of MTBI by adding 3 brief scanning sessions during the first week of injury (roughly days 3-4, 5-6 and 7-8) to those performed by the PPG (i.e., within 48 hours of injury and at 3 months post-injury).
Specific Aim 1 examines the extent, duration, and timing of acute/subacute changes in brain parenchyma detectable via MR imaging modalities including DTI and MTI in participants with MTBI and ModTBI.
Specific Aim 2 evaluates the degree to which initial changes detectable via imaging are related to injury severity, PCS symptom severity, and reaction time (RT) during this subacute period. Finally, Specific Aim 3 attempts to determine if the maximal point of deviation from presumed baseline for DTI and MTI in the subacute period is predictive of 3-month outcome on imaging and measures of PCS and RT. If the extent of initial change detected by these imaging modalities was found to be related to 3-month outcome, they could serve as diagnostic indicators of MTBI identifying patients at risk for incomplete resolution of PCS symptoms who require early intervention. Understanding the extent and duration of these initial changes could be critical in selecting and evaluating treatment interventions and critical windows for intervention if they are presumed to target the kinds of pathophysiology that advanced imaging can detect in the acute stages.

Public Health Relevance

Symptoms of mild traumatic brain injury (MTBI) including headaches, dizziness, and problems thinking, usually resolve in the first few months after injury;however, some patients may have symptoms that do not go away for a long time. Studies have shown that damage to the brain after MTBI can be seen with advanced magnetic resonance imaging methods (MRI). The goal of the study is to use imaging methods in four sessions over the first 7-8 days following a MTBI which will give us a better understanding of the order and pattern of changes happening in brain tissue, how they relate to the patient's symptoms and thinking ability, and how they relate to mental and physical functioning 3 months after MTBI.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Small Research Grants (R03)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Hicks, Ramona R
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Baylor College of Medicine
Physical Medicine & Rehab
Schools of Medicine
United States
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Gonzaga-Jauregui, Claudia; Lotze, Timothy; Jamal, Leila et al. (2013) Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly. JAMA Neurol 70:1491-8
Wilde, Elisabeth A; McCauley, Stephen R; Barnes, Amanda et al. (2012) Serial measurement of memory and diffusion tensor imaging changes within the first week following uncomplicated mild traumatic brain injury. Brain Imaging Behav 6:319-28