The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) neurological exam and magnetic resonance imaging (MRI) ?the prevailing methods to assess severity of injury and predict prognosis? suffer from significant limitations and often fail to accurately predict long-term outcome in individuals, and neither provides information on the functional and physiological viability of residual cord tissue altered by the injury. Using standard MRI, physicians may grossly under/overestimate the degree of intrinsic cord injury or functional connectivity of cord tissue. Thus, these widely used clinical and radiological assessments are often unable to distinguish between incomplete and complete injuries and more sensitive determinants of long-term outcomes are critically needed. Diffusion tensor imaging (DTI) is an MRI technique that has shown promise in estimating the degree of axonal injury in acutely injured cord in both animal and limited human studies. However, fractional anisotropy (FA), a key DTI parameter that is reduced in acute SCI, is confounded by edema and hemorrhage making its interpretation and reliability problematic. A novel diffusion MRI alternative, double diffusion encoding (DDE), has shown high sensitivity to axonal injury with minimal contribution from edema and accurately predicts outcomes in a rat SCI model. However, rodent models of SCI are limited, and it remains uncertain if DDE performs as reliably in a large animal model more faithfully replicating human SCI. Furthermore, the relationship between DDE and electrophysiological activity, which is critical to establishing the functional integrity or neural conduction block across the injury site, has not been explored. Our goal is to enhance the translational applicability of DDE using a validated large animal porcine contusion model currently being used by our group. Preliminary MRI data from our group using this model matches both the quality and challenges of human SCI imaging. To relate DDE-derived axonal injury index (ADC||) with neural function, we will conduct both DDE assessments and intraoperative D-wave epidural electrophysiology in a porcine contusion SCI model with mild (n=6) and severe (n=6) injury. Successful project completion will lead to direct translation to human SCI patient studies with the long-term goal of improving patient outcomes from such a devastating injury.
The overall goal of this application is to enhance the ability to predict outcomes in acute traumatic SCI. The proposed experiments will capitalize on our expertise using a large animal model of SCI to establish the relationship between quantitative diffusion MRI metrics of axonal injury, histology, electrophysiological function and long-term neurological outcomes. Successful completion of the project will lead to direct translation to human SCI patient studies with the long-term goal of improving acute management and patient outcomes from such a devastating injury.
