Evaluation of Spinal Cord White Matter Injury Using DTI

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DESCRIPTION (provided by applicant): Spinal cord injury (SCI) is one of the most devastating traumatic events. More than 200,000 Americans are living with SCI resulting from automobile accidents, sports injuries, and other trauma. Since white-matter lesions of the spinal cord usually result in paralysis and sensory loss in SCI patients, it is crucial that non-invasive modalities be developed to provide a detailed assessment of the underlying pathology of SCI. Further, as new therapies are developed, it is important to have indicators of white matter injury as surrogate markers for degree of damage and therapeutic response. The analytical use of diffusion tensor imaging (DTI) proposed herein may provide one such indicator and is consistent with our broader goal of developing DTI technology to help improve the quality of life of SCI patients. DTI has been widely applied in central nervous systems (CNS), providing detailed analysis of tissue morphology and pathology. Increased use of DTI in spinal cord injury for assessment of severity and progression of the damage has also been seen in recent years. However, conventional use of DTI has not addressed the more pressing need to non-invasively detect and differentiate underlying pathologies of the CNS white matter injury, i.e., axonal injury, demyelination, and inflammation. In this study, we propose to use the currently available DTI technology to establish a direct link between directional diffusivities and underlying white matter pathologies during SCI. Specifically, we will use mouse models of SCI with highly-specific, well-defined pathology to quantify DTI parameters relating primarily: myelin degeneration (Aim 1), axonal injury followed by demyelination (Aim 2), and inflammation with/without axonal and myelin injury (Aim 3). It is expected that myelin degradation will precede axonal injury in Aim 3 of inflammation with axonal and myelin injury, in contrast to Aim 2 in which we expect axonal injury followed by demyelination. In vivo DTI findings will be validated by histological analysis including myelin staining, axonal staining, and transmission electron microscopy (EM).