Jak, Amy: Novel White Matter Imaging to Improve Diagnosis of Mild TBI Abstract Mild traumatic brain injury (mTBI), also knows as a concussion, is prevalent in military personnel and has been deemed the ?signature injury? of the conflicts in Iraq and Afghanistan. Cognitive complaints, headaches, nausea, and dizziness, among others, are common and expected symptoms following mTBI. These symptoms resolve within 7-10 days in most individuals, though 90 days is often referenced as the duration of ?normal? recovery after a mild TBI. However, 15-30% of individuals do not recover along this timeline and experience persistent post-concussive symptoms. Psychological factors have been shown to play a substantial role in the persistence of post-concussive symptoms beyond 90 days. Because post- traumatic stress disorder (PTSD) is also highly prevalent in combat Veterans and highly comorbid with mTBI in this population, it has been difficult to tease apart the etiology of persistent cognitive symptoms in the comorbid group and determine if remote history of concussion is contributing to current behavioral symptoms or if the presentation is driven by mental health factors. Traditional structural neuroimaging techniques are largely insensitive to the subtle damage resulting from mTBI. Newer magnetic resonance imaging (MRI) acquisition methods such as Diffusion Tensor Imaging (DTI) have shown more promise in identifying changes in white matter integrity following mTBI. However, even this advanced technology produces equivocal results, has revealed changes in white matter integrity in both mTBI and PTSD, and lacks the sensitivity or specificity to identify the underlying cause of any white matter changes. This proposal, therefore, will utilize a new approach for assessment specifically of myelin abnormalities, multicomponent-driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT), to calculate myelin volume in vivo. We propose to conduct neuroimaging using standard structural and diffusion tensor imaging (DTI) as well as mcDESPOT on 82 Veterans with a history of mTBI, PTSD, or both, as well as controls. We will also serve as a coordinating site for post-processing and analysis of mcDESPOT data collected at other consortium sites. We hypothesize that mcDESPOT will be more sensitive and specific to mTBI than DTI and persistent cognitive symptoms in those with a history of mTBI will correlate more strongly with mcDESPOT findings. There have been no published reports using mcDESPOT in TBI and if this imaging sequence demonstrates improved sensitivity and specificity over current white matter imaging techniques, it could emerge as a way to disentangle TBI-related residual brain damage from mental health driven symptoms as well as to identify individuals who may be at higher risk for poor recovery after mTBI.
The goal of the project is to generate a deliverable novel neuroimaging technique that can better identify mTBI and etiology of persistent post-concussive symptoms. We will utilize mcDESPOT to specifically calculate myelin volume in vivo in a sample of Veterans with mTBI, PTSD, or both, and controls, to improve our ability to differentiate TBI from mental health etiologies for persistent post- concussive symptoms, improve our understanding of the pathophysiology of mild TBI in humans, and enhance prognosis and treatment planning. If mcDESPOT demonstrates improved sensitivity and specificity in this population, this 12 minute MRI sequence can serve as deliverable clinical tool for diagnosis and prognosis of mTBI. This technique holds the possibility of better characterizing and understanding the sizeable minority of cases that do not resolve along expected trajectories following mTBI which will subsequently lead to better and more targeted interventions for these symptoms.
