Vascular plasticity in Injured Spinal Cord-Investigations using MRI

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DESCRIPTION (provided by applicant): Spinal cord injury (SCI) is a major health and socio-economic problem, affecting many individuals. Magnetic resonance imaging (MRI) provides in vivo three-dimensional images with exquisite soft tissue contrast for investigating injured spinal cord (SC). In experimental studies with rat models of SCI, we regularly use MRI to follow the same animal longitudinally, so that each animal can serve as its own control. Conventional MRI, however, provides limited information on vascular changes that occur transiently following the injury. Novel imaging methods with capacity to sense vascular changes are required. As potential imaging approaches, we have recently explored MR angiography (MRA) and perfusion MRI (P- MRI) techniques for probing the vascular system of rat SC. Our preliminary data showed that MRA is capable of producing high-resolution maps of macrovascular projections that supply blood to the rat SC while P-MRI is sensitive to the microvasculature within the cord tissue. Using the contrast agent gadopentate dimeglumine (Gd), we also generated angiograms that delineate the spinal vessels in greater detail. In longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies, we have previously quantified the temporal changes in permeability of blood-spinal cord barrier (BSCB) following the injury and detected the neovasculature in injured cord. Based on these preliminary results, we hypothesize that the combination of the imaging modalities (anatomical MRI, MRA, P-MRI and DCE-MRI) will increase the reliability, sensitivity and specificity of detecting morphological and vascular changes in injured SC. The MR-based measurements will provide valuable direct information on pathology, physiology and function of injured SC non-invasively, and may serve as a predictor of the final neurologic outcome from SCI. To test this hypothesis, we will perform high resolution in vivo imaging using implantable radio frequency coil in longitudinal studies of SC on injured and control rats. In conjunction with imaging, we will also carry out standard neurobehavioral tests on the animals recovering from the injury and perform quantitative end-point histological analysis on the injured cord tissue. We will statistically compare the MR-based measurements with the behavioral scores and histological findings to determine the endogenous vascular plasticity in injured SC and its role in recovery from SCI. A non-invasive determination of reorganization in vascular network of SC that is associated with the recovery of function following SCI will be a large step forward in understanding the recovery mechanisms, and in long term, objective assessment of potential new therapies with power to manipulate the SC vasculature with or without the use of exogenous processes to improve the neurofunctional outcome.