Functional Ultrasound Imaging Reveals Activation Properties of Clinical Spinal Cord Stimulation

Abstract

ObjectivesSpinal cord stimulation (SCS) therapy has long been established as an effective treatment for chronic neuropathic pain. However, methodological limitations have prohibited the detailed investigation of the activation patterns produced in the spinal cord during therapy. Functional ultrasound (fUS) is an emerging technology that monitors local hemodynamic changes in the brain that are tightly coupled to neural functional activity [1-3]. Previous studies have demonstrated that the high sensitivity and spatiotemporal resolution of fUS can be used to monitor activation in the spinal cord [4, 5]. In this study, fUS was used to investigate neuromodulation patterns produced by clinical SCS paradigms in an ovine model that enabled testing with implanted clinical hardware. Materials and MethodsActivation of local dorsal horn regions during SCS therapy was evaluated using fUS to detect hemodynamic changes in flowing spinal blood volume ({Delta}SBV). Briefly, male ovine subjects were anesthetized and laminectomies were performed at T12-L1 to expose the spinal cord. The spine was mechanically fixed to reduce breathing-induced motion. Standard SCS leads were percutaneously implanted midline overlying the dura of the exposed cord to enable stimulation and recording. A second lead was implanted in the epidural space anterior to the laminectomy for recording evoked compound action potentials (eCAPs). Motor thresholds were determined from electromyographic (EMG) signals recorded from subdermal needle electrodes. Hemodynamic activation patterns produced by SCS therapy were mapped across two vertebral segments in the superficial dorsal horn (SDH) at amplitudes between 100%-200% eCAP threshold (eCAPT). The magnitude and volume of significant {Delta}SBV during SCS was quantified and compared across conditions. ResultseCAP and motor thresholds varied widely between different representative SCS programs in current clinical use. Compared with motor threshold, we found eCAPT to be a more stable and reliable ratiometric reference to establish neural drive from stimulation, consistent with previous literature [6]. SCS stimulation resulted in significant activation of the SDH in differing patterns across two vertebral segments. The magnitude and volume of {Delta}SBV increased at higher amplitudes and was typically maximal in the SDH regions underlying the active electrodes. Activation persisted for several seconds following SCS therapy cessation, suggesting the engagement of neurophysiological processes with correspondingly long time constants. In addition, therapy mode significantly influenced total area and depth of {Delta}SBV. Multiphase therapy produced a larger area of {Delta}SBV that extended deeper into the spinal cord relative to single phase therapies. ConclusionsThis work demonstrates that fUS can effectively measure SCS neural response patterns in the pain processing laminae of a large animal model implanted with a clinical SCS system. Hemodynamic responses in the spinal cord varied significantly across SCS therapy modes, with Multiphase stimulation providing a greater area of coverage and depth of response versus other common stimulation types.