While there is understandably much excitement around novel neuroprotective drugs and neuroregenerative technologies for acute spinal cord injury (SCI) (e.g., stem cells), the reality is that the newly injured patient who arrives in emergency wants to know what can be done now to potentially improve their spinal cord paralysis. Sadly, one of the only treatment options for acute SCI patients is the elevation of blood pressure to maintain blood supply to the injured spinal cord. Exciting data published very recently have shown that even small differences in average blood pressure can influence whether an acute SCI patient improves from being "completely paralyzed" to "incompletely paralyzed." Equally intriguing (also recently published) data show that while an increase in blood pressure for one patient might improve his/her spinal cord blood flow, such an increase might not be sufficient for another patient (or conversely it might actually be too high). Adhering to simple guidelines that suggest a target blood pressure that should be maintained in all patients might therefore improve outcome in some but worsen it in others. What is lacking for clinicians who are treating such patients is a measurement tool that provides real-time information about the spinal cord blood supply and oxygenation and allows them to know if their efforts to elevate blood pressure are actually improving (or worsening) the injured spinal cord. Such a tool would provide information to guide clinicians in their treatment decisions and allow them to personalize the hemodynamic management of acute SCI patients to optimize neurologic outcome.

In this project, we will explore the potential of near-infrared spectroscopy (NIRS) as a monitoring tool to provide this information, with an explicit goal of developing this technology into a device that can be used in human SCI patients. NIRS works by shining near-infrared (NIR) light through tissues and then recording how much light gets transmitted versus how much gets absorbed by molecules within the tissue. One of the important molecules within tissue that absorbs NIR light is hemoglobin (Hgb), which is the molecule that carries oxygen within the bloodstream. The absorption of NIR light by Hgb depends on whether Hgb is oxygenated or not. Thus, by measuring near infrared light absorption in tissue, NIRS can measure how much oxygen and blood is being delivered and can potentially inform us of whether cells within the tissue are being irreversibly injured due to oxygen deprivation.

These properties of NIRS have already been exploited for measuring oxygen levels in the brain in settings where blood supply and oxygen to the brain can be compromised (such as traumatic brain injury, during cardiac surgery, and in neonatal/pediatric intensive care). We therefore believe that NIRS is a promising technology to explore for acute SCI. Our goal is to develop a NIRS system that can be easily placed on top of the injured spinal cord by the surgeon after performing decompression/stabilization surgery. This can then be left in place to monitor spinal cord oxygenation and blood supply over the ensuing days. When the monitoring period comes to an end, the probe can simply be removed by pulling it out, similar to how wound drains are removed.

In developing such a system, one would naturally ask, "How good is it at measuring the oxygen and blood supply of the spinal cord after injury?" To address this, we will evaluate NIRS in a pig model of SCI. The pig spinal cord is much more similar in size and general anatomy to the human spinal cord than the rodent. We have established techniques for measuring oxygen, blood flow, pressure, and metabolism within the spinal cord with small needle-like monitoring probes that we insert directly inside the spinal cord. We therefore will have the opportunity to evaluate how "effective" NIRS is by comparing the measurements obtained from a noninvasive NIRS sensor placed outside the spinal cord with those obtained from monitoring probes inserted inside the spinal cord. We will do this initially within the controlled setting of the operating room in anesthetized animals. This information will guide the technology development of the NIRS system itself, during which we anticipate miniaturizing the sensors to create a device that can be used in a human patient. This refined NIRS device will then be evaluated in our pig model of SCI but over a more clinically realistic 7-day post-injury period where the animal will be allowed to recover from the surgery. Again, our techniques for doing invasive measurements of oxygen, blood flow, and pressure over 7 days in awake animals gives us the opportunity to evaluate how well NIRS measures these physiologic parameters. Finally, we will refine the system for evaluation in a human patient and prepare the necessary ethics applications to conduct a clinical trial.

This project has a clear goal of translating a promising technology (NIRS) into a clinical application for acute SCI patients. Our initiative is focused on providing a tool that will assist clinicians in their hemodynamic management of acutely injured patients during a time when their efforts to support oxygenation and perfusion of the spinal cord can indeed improve neurologic outcome.