High Resolution MRI Mapping of CNS Plasticity Following Spinal Cord Injury in Primates

Lay Summary

Imaging results may predict extent of spinal cord injury recovery

Investigators will determine whether leading edge MRI imaging techniques in a non-human primate model of spinal cord injury can be used to predict the extent of subsequent functional recovery.

About one-half of all spinal cord injuries result in quadriplegia. Experimental evidence increasingly suggests that the central nervous system (CNS) undergoes substantial reorganization that may play a critical role in determining the degree of functional recovery that an injured patient achieves. Particularly important may be plasticity that occurs in the cortex and thalamus. Both are involved in the brain’s somatosensory system, which conveys information that the brain uses to perceive experiences such as touch and pain. Nonetheless, little is currently known about how patients’ outcomes correlate with specific changes in plasticity in these areas. This is due in part to the complexity of the research and also to limitations of investigative tools. The research group in this field at Vanderbilt is pioneering refinements in structural and functional imaging techniques to characterize the role of CNS reorganization in functional recovery. They hypothesize that severity of the spinal cord damage, and degree and spatial extent of the plasticity that occurs in the cortex and thalamus, determine the degree of functional recovery.

They will test this hypothesis using state-of-the-art imaging techniques before and after injury in the experimental animal model, and in comparison non-injured primates to determine whether high resolution MRI can monitor and quantify CNS plasticity changes in cortex and thalamus over time; and, whether Diffusion Tensor Imaging (DTI), which assesses injury severity, can predict the plastic changes that are observed in the pathways in these regions. If so, they will determine what plasticity changes over time correlate with deficits and recovery.  They will validate their imaging findings by comparing them to those obtained through functional optical imaging of intrinsic brain signals, brain mapping through electrical recording, and analyses of the animals’ autopsied brain tissues. If the investigators find that the MRI and DTI techniques validly demonstrate an ability to identify the brain correlates of functional recovery from spinal cord injury, results will lead to, and aid in the interpretation of, this imaging in spinal cord injured patients to predict the likely extent of their recovery and responses to therapeutic interventions.

Abstract

High Resolution MRI Mapping of CNS Plasticity following Spinal Cord Injury in Primates

There is compelling evidence that following spinal cord injury (SCI) the capacity for plastic reorganization exists at multiple relay stations (brainstem, thalamus, cortical sensorimotor areas) in the ascending and descending pathways and that these reorganizations can influence the long-term functional and behavioral outcomes.  Currently the ability to gain a detailed understanding of the role of plastic remodeling in central nervous system (CNS) is limited on the one hand by the lack of effective tools for monitoring these changes non-invasively, and on the other by the heterogeneity of the location and severity of the SCI in the clinical population. The significance of the research proposed here is that we will apply our recent advances in structural and functional MRI at ultra-high fields (e.g. at 9.4T), which include sub-millimeter resolution functional mapping in the nonhuman primate brain, and high angular resolution diffusion imaging (HARDI) of white matter tracts in the cord and brain, to characterize the evolution of a spinal cord injury and the trajectory of plastic reorganization in the CNS, in a well characterized non-human primate model of SCI. By comparing these MR findings with electrophysiological, optical imaging, and behavioral data collected in vivo, and histological data collected post mortem from the same animal, we will be able to validate the imaging findings, providing a basis for future MR-based studies of the nature and influence of plastic remodeling following SCI in human subjects.