This proposal aims to establish perfusion magnetic resonance imaging (MRI) of the spinal cord as a translational tool and predictive biomarker of secondary damage after acute spinal cord injury (SCI). In SCI, minimizing damage that occurs beyond the initial insult (i.e. secondary injury) is considered a primary therapeutic target. Current clinical recommendations for acute SCI care advocate restoration of spinal cord perfusion to reduce secondary injury and provide the greatest chance for improved neurological outcome. However, spinal cord perfusion status is not routinely monitored in SCI patients, and the lack of noninvasive tools considerably impedes personalized care in SCI. Remarkably, while perfusion magnetic resonance imaging (MRI) of the brain has been reported in 100s of studies, there is almost a complete void of perfusion MRI studies applied to the spinal cord despite its high potential to improve patient outcomes. We previously showed that diffusion MRI of the rodent spinal cord, with contrast uniquely sensitized to axonal injury, could predict injury severity and neurological outcomes with high accuracy. With our recent advances in high resolution diffusion MRI, the location and extent of injury within the cord was visualized with detail in individual subjects. Thus, our central hypothesis is that while diffusion MRI detects irreversible injury acutely after SCI, perfusion MRI deficits reflect tissue at risk of secondary injury in the absence of an intervention. Our preliminary studies demonstrate the feasibility of obtaining high resolution perfusion MRI of the thoracic spinal cord. We propose to use in vivo MRI in a rat model of contusion SCI to (Aim 1) enhance and tailor perfusion MRI to the spinal cord for accurate, efficient, and high-resolution interrogation of perfusion status, (Aim 2) characterize perfusion and diffusion deficits after acute spinal cord traumatic injury in the rat to distinguish between reversible and non-reversible injury, and (Aim 3) demonstrate the utility of perfusion MRI to noninvasively monitor clinically-recommended interventions. Overall, these studies will provide a strong technical and scientific foundation to promote translational use of advanced MRI for personalized care of SCI patients. These translational studies aim to realize the full clinical utility of noninvasive imaging to maximize outcomes from such as devastating injury and its detrimental impact on quality-of-life.
Spinal cord injury is a devastating injury, and medical care within the early acute care setting can critically affect outcome. This project will advance the ability to monitor perfusion of the spinal cord with MRI and demonstrate its role in predicting risk of further injury and outcomes from SCI.