The goal of this project is to develop detailed measures of the severity of axon damage using magnetic resonance (MR) imaging. The applicants proposed to test the hypotheses that advanced MR techniques will permit detailed non-destructive characterization of the nature and severity of structural damage in an experimental model of spinal cord injury, that these MR measures will predict functional recovery and that this characterization will be more precise than that available from knowledge of the severity of mechanical injury or routine MR imaging. The applicants proposed to employ a weight-drop model of spinal cord injury in Sprague-Dawley rats. Several injury intensities will be used. In-vivo MR imaging will be performed on a small-bore 1.9 Tesla instrument using an inductively-coupled, implanted surface coil system. Magnetization transfer (MT) contrast studies will include measurement of percent MT contrast in normal cords and in injured cords. Apparent diffusion coefficient (ADC) studies will include diffusion measurements along the long axis of the spinal cord (longitudinal-1ADC) and perpendicular to this (transverse-tADC). Serial MR studies, including MT and ADC measurements, will be performed in vivo at 4 and 24 hours, as well as 3,7,14,21,28 and 56 days after injury. This data will be correlated with periodic assessment hind limb function using the Combined Behavioral Score and a set of structural parameters including: the number of preserved axons at a cross-sectional level of the cord, the distribution of axon diameters (the proportion of axons with diameters in several size classes from less than 1 micron to greater than 5 microns), the distribution of myelin sheath thickness, myelination index of """"""""g ratio"""""""" (the ratio of myelinated fiber diameter to axon diameter), status of the myelin sheath (normal, loosening of lamellae, vesiculation, sloughing or destruction of myelin), integrity of the axon membrane, and the presence and polymerization status of neurofilament proteins. The hypothesis is that MT findings will predict neurofilament and myelin sheath alterations while ADC studies will predict axon diameter, spacing, and membrane and myelin damage. Using a simple model of the diffusion process, the applicants proposed to employ the pattern of changes in 1ADC and tADC to infer alterations in axonal structure in response to injury.
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