This is a Shannon Award providing partial support for the research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon Award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. The goal of this project is to develop detailed measures of the severity of axon damage using magnetic resonance (MR) imaging. We will test the following hypotheses: 1. In cases of acute spinal cord injury, the severity of axon damage is related to the severity of acute and subacute functional deficits, and to the potential for recovery of function over time. 2. Magnetization transfer (MT) contrast and diffusion characteristics (longitudinal and transverse apparent diffusion coefficients and anisotropy) of the spinal cord white matter reflect the integrity of the myelin sheaths, the extent of axon swelling and the number of surviving axons. Magnetization transfer contrast is also determined, in part, by the presence and polymerization status of neurofilament proteins. 3. Magnetization transfer contrast and diffusion characteristics determined shortly after injury contribute to prediction of: a. the severity of functional deficits at later time points and b. the rate of recovery. In order to test these hypotheses, we will employ a weight-drop model of spinal cord injury in Sprague-Dawley rats. Several injury intensities will be used. MR imaging will be performed using an inductively-coupled, implanted surface coil system. Serial MR studies, including MT and diffusion 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 and histologic measures including: the number of preserved axons at a cross-sectional level of the cord, distribution of axon diameters, i.e. the proportion of axons with diameters in several size classes from less than 1 micron to greater than 5 microns, distribution of myelin sheath thickness, the ratio of myelinated fiber diameter to axon diameter (""""""""myelination index"""""""" or """"""""g-ratio""""""""), status of the myelin sheath, i.e. normal, loosening of lamellae, vesiculation, sloughing and destruction of myelin and presence and polymerization status of neurofilament. We will determine the extent to which MR measures predict histologic and functional outcomes.
