Abstract The integration of functional responses in the human spinal cord into the nervous system is not well understood. Herein we demonstrate the first in-human functional ultrasound imaging (fUSI) of spinal cord response to epidural electrical stimulation. fUSI is a minimally invasive neuroimaging technique that can record blood flow at a level of spatial and temporal precision not previously achieved in the human spinal cord. By leveraging fUSI and epidural electrical spinal cord stimulation in patients who underwent surgery, we recorded and characterized for the first-time hemodynamic responses of the human spinal cord to an electrical neuromodulatory intervention commonly used for treating pain, and increasingly used for sensory-motor and autonomic functions. We found that the hemodynamic response to epidural stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized. The impact of this analytical capability is significant for several reasons. It offers a mechanism to assess blood flow changes with a new level of precision which can be obtained in real time under in vivo conditions. Additionally, we demonstrate that fUSI can successfully decode the spinal cord state in a single trial, which is of fundamental importance for developing real-time closed-loop neuromodulation systems. Also, we show that spinal cord hemodynamic changes due to epidural electrical stimulation occur primarily at the level of small vessels. Overall, our work is a critical step towards developing a vital technique to study spinal cord function and understand the potential effects of clinical neuromodulation for spinal cord and other neurological disorders. One Sentence Summary The first in-human quantitative evaluation of spinal cord hemodynamics using functional ultrasound imaging (fUSI).

Functional Ultrasound Imaging of the Human Spinal Cord