Magnetic resonance imaging (MRI) provides in vivo 3D images of rat spinal cord (SC) with exquisite soft tissue contrast, and allows following the same animal longitudinally in experimental spinal cord injury (SCI) studies. Conventional MRIs, however, give limited information and new neuroimaging methods are required for visualizing the neural network of injured SC. Experienced with the use of MR contrast agents in our previous SCI studies, we have investigated manganese-enhanced MRI (MEI) with the potential to produce high-resolution maps of the neural fiber projections in normal and injured cords. Our initial data showed that the contrast agent manganese (Mn) spreads in both rostral and caudal directions in normal cord. In hemisectioned SCs, Mn is transported below the lesion on the contra-lateral, but not ipsilateral, to the cut. This was also confirmed by parallel studies with histological neuronal tracer. In a contusion-type SCI model, Mn labeling was detected within and below the injury, possibly due to the presence of viable tissue therein. In recent experiments, we delivered Mn into the cortex or brainstem of normal and injured rats. With intracortical injection, weak labeling was observed in the descending spinal tracts below the pyramidal decussation. But, injection to brainstem successfully produced sensitive and specific labeling in the targeted fibers. The sections of injured cord below the injury were labeled with Mn, suggesting some fibers were bridging across the injury. From these aspects, MEI offers a new tool for detecting live fibers (spared/restored) in injured SC, and may play a role in validating the accuracy of diffusion tensor imaging (DTI) in sensing these fibers. Based on these results, we hypothesize that DTI corroborated with MEI may provide crucial information on the spatiotemporal dynamics of the changes in the fiber connections during the course of recovery from SCI. To test this hypothesis, we propose to investigate normal and injured SCs using MEI, DTI and high resolution MRI along with neurobehavioral tests and end point histological analysis. These multi-modal studies will establish a new modality to probe the evolution of SCI and map the fiber projections. This should form a basis for future experimental investigations aimed at testing new therapies for promoting fiber connectivity, understanding SC plasticity and improving functional recovery from SCI. ? ? ?
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