Abstract
This study presents the first implementation of functional ultrasound (fUS) imaging of the spinal cord to monitor local hemodynamic response to epidural electrical spinal cord stimulation (SCS) on two small and large animal models. SCS has been successfully applied to control chronic refractory pain and recently was evolved to alleviate motor impairment in Parkinson's disease and after spinal cord injury. At present, however, the mechanisms underlying SCS remain unclear, and current methods for monitoring SCS are limited in their capacity to provide the required sensitivity and spatiotemporal resolutions to evaluate functional changes in response to SCS. fUS is an emerging technology that has recently shown promising results in monitoring a variety of neural activities associated with the brain. Here we demonstrated the feasibility of performing fUS on two animal models during SCS. We showed in vivo spinal cord hemodynamic responses measured by fUS evoked by different SCS parameters. We also demonstrated that fUS has a higher sensitivity in monitoring spinal cord response than electromyography. The high spatial and temporal resolutions of fUS were demonstrated by localized measurements of hemodynamic responses at different spinal cord segments, and by reliable tracking of spinal cord responses to patterned electrical stimulations, respectively. Finally, we proposed optimized fUS imaging and post-processing methods for spinal cord. These results support feasibility of fUS imaging of the spinal cord and could pave the way for future systematic studies to investigate spinal cord functional organization and the mechanisms of spinal cord neuromodulation in vivo.
Highlights
Over the last decades, epidural electrical spinal cord stimulation (SCS) was successfully implemented to help patients with chronic intractable pain [1,2,3]
One can clearly see that higher SCS voltages produced stronger spinal cord hemodynamic responses
The importance of understanding the physiological and pathological mechanisms of the spinal cord hemodynamic regulation is critical for diagnostics, for clinical monitoring, and for developing novel therapies and new rehabilitation protocols
Summary
Epidural electrical spinal cord stimulation (SCS) was successfully implemented to help patients with chronic intractable pain [1,2,3]. The mechanisms and neural structures through which SCS inhibits chronic pain and enables motor control remain unclear, several hypotheses were supported by computational simulations [16,17,18] and data, primarily obtained from electrophysiological recordings [19, 20]. The EMG signal is limited and can provide one-dimensional information concerning the activation of spinal cord neurons. In this context, a combination of emerging, innovative techniques providing high spatial and temporal resolution, and electrophysiology techniques could provide critical information on mechanisms of SCS and further facilitate optimizations of SCS protocols. The spatial resolution of functional magnetic resonance imaging (fMRI) reaches submillimeter with ultra-high magnetic field [21, 22], the size of MR machine can be prohibitive for an intraoperative monitoring
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