This proposal addresses the development of nuclear magnetic resonance (NMR) spectroscopy and imaging techniques for application to in vivo studies of spinal cord injury (SCI) and functional repair.
Three aims are proposed that will test the hypothesis that serial, non-invasive NMR measurements in individual animals can identify tissue parameters that reflect the time-course of lesion stabilization as well as the success of intraspinal grafting methods.
The first aim i s to develop: (a) diffusion- sensitive NMR imaging; (b) localized 1/H NMR spectroscopy; and (c) implanted radiofrequency (RF) reception coils that can be used to monitor tissue dynamics associated with spinal cord injury and transplantation. These NMR methods will then be used to address specific biological issues pertaining to spinal cord injury and repair with intraspinal fetal grafts. Therefore, the second aim is to obtain reliable, repeated measures of several anatomical (diffusion weighted images, T/1 and T/2 mapping) and neurochemical indices (1/H NMR spectra of lipids, lactate, N-acetyl compounds, and choline) of SCI. This information will be used to: (a) establish the evolution of the lesion; (b) determine the time after injury at which stabilization of spinal cord pathophysiology occurs; and (c) investigate the extent to which various NMR indices of lesion development and biochemical change correlate with functional outcome. The last aim of this project involves studies to: (a) evaluate the maturation, host-graft integration and long-term survival of intraspinal grafts of fetal neural tissue using the NMR approaches outlined in Aim 2; and (b) correlate these NMR parameters with histological assessments of host and graft tissues and measures of locomotor performance.
