Functional Ultrasound Imaging Reveals Activation Properties of Clinical Spinal Cord Stimulation Therapy Programming

Spinal cord stimulation (SCS) therapy is an established treatment for chronic neuropathic pain, but methodological limitations have prohibited detailed investigation of activation patterns it produces in the SC. Functional ultrasound imaging (fUS) is an emerging technology that monitors local hemodynamic changes in the brain with high sensitivity and spatiotemporal resolution that are tightly coupled to neural functional activity. 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. Activation of local superficial dorsal horn (SDH) regions during SCS therapy was evaluated using fUS to detect hemodynamic changes in spinal blood volume (∆SBV). Standard SCS leads were percutaneously implanted midline overlying the dura of the exposed cord (T12-L1) to enable stimulation and recording evoked compound action potentials (eCAPs). Hemodynamic activation patterns were mapped across two vertebral segments at amplitudes between 100-200% eCAP threshold for conventional tonic, multiphase, burst, high frequency and multi-frequency SCS paradigms. SCS stimulation resulted in significant activation of the SDH in differing patterns across two vertebral segments. The magnitude and volume of ∆SBV increased at higher amplitudes and was typically maximal in the SDH regions underlying the active electrodes. Therapy mode significantly influenced total area and depth of ∆SBV. Multiphase therapy produced the largest area of ∆SBV followed by multi-frequency and other SCS modes. Multiphase therapy also produced the greatest depth of ∆SBV followed by multi-frequency and burst therapies. This 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 SC varied significantly across SCS therapy modes, with multiphase stimulation providing a greater area of coverage and depth of response versus other common stimulation types.