While mild traumatic brain injury (mTBI) has become the focus of many neuroimaging studies, the understanding of mTBI, particularly in patients who evince no radiological evidence of injury and yet experience clinical and cognitive symptoms, has remained a complex challenge. Sophisticated imaging tools are needed to delineate the kind of subtle brain injury that is extant in these patients, as existing tools are often ill-suited for the diagnosis of mTBI. For example, conventional magnetic resonance imaging (MRI) studies have focused on seeking a spatially consistent pattern of abnormal signal using statistical analyses that compare average differences between groups, i.e., separating mTBI from healthy controls. While these methods are successful in many diseases, they are not as useful in mTBI, where brain injuries are spatially heterogeneous. The goal of this proposal is to develop a robust framework to perform subject-specific neuroimaging analyses of Diffusion MRI (dMRI), as this modality has shown excellent sensitivity to brain injuries and can locate subtle brain abnormalities that are not detected using routine clinical neuroradiological readings. New algorithms will be developed to create Individualized Brain Abnormality (IBA) maps that will have a number of clinical and research applications. In this proposal, this technology will be used to analyze a previously acquired dataset from the INTRuST Clinical Consortium, a multi-center effort to study subjects with Post- Traumatic Stress Disorder (PTSD) and mTBI. Neuroimaging abnormality measures will be linked to clinical and neuropsychological assessments. This technique will allow us to tease apart neuroimaging differences between PTSD and mTBI and to establish baseline relationships between neuroimaging markers, and clinical and cognitive measures. Upon completion of this project, a set of tools, which have the potential to establish radiological evidence of brain injury in mTBI, will have been designed and evaluated, thereby enhancing both the diagnosis and monitoring of progression/recovery of injury, as well assessing the efficacy of therapies on the injured brain.
One major limitation to standard clinical care is that imaging methods used routinely for diagnosis are not sensitive enough to detect the subtle pathologies of mild Traumatic Brain Injury (mTBI). The overarching goal of this proposal is to design tools to create individualized brain injury maps from diffusion MRI that can detect these subtle abnormalities, and help establish a link between imaging and symptomatology in mTBI.