Focused Ultrasound Neural Stimulation for Spinal Cord Injury
Abstract
Spinal cord injury (SCI) is often the result of trauma sustained in battlefield injuries and causes loss of sensory, motor, and autonomic functions below the site of the injury. SCI often results in loss of voluntary control of bladder function, which we propose to address with our novel self-focusing acoustic transducer (SFAT), as regaining bladder control is one of the top priorities for functional recovery in SCI patients and since neuronal activation using intraspinal stimulation with focused acoustic beam has the potential to restore control of the bladder voiding. Neuronal activation by electrical stimulation has been employed to treat neurological disorders including deafness, blindness, Parkinson’s disease, essential tremor, and epilepsy, either by vagus nerve stimulation or by stimulation applied at sites in the deep brain. However, though penetrating-type microelectrodes allow high spatial resolution of the electrical stimulation, they are invasive and cause foreign-body responses. A consistent finding from the histologic evaluation of electrode implantation sites is the gradual loss over time of neurons within approximately 50-70 microns of the microelectrodes, which can reduce the effectiveness of the applied electrical stimulus. Surface electrodes, while less invasive, lack the ability to generate a highly localized electrical field. In recent years, electrical stimulation of the spinal cord has been applied with the goal of restoring control of micturition after SCI. In this approach, the stimulated substrate is a ventral root (or roots), which contains mixed efferent projections to the bladder, the external urethral sphincter (EUS), and other somatic and visceral muscles. Continuous electrical stimulation of the ventral roots produces little voiding due to a coincident activation of the bladder and closing of the bladder outlet from constriction of the EUS. This problem is further exacerbated by the fact that the large fibers innervating the EUS and somatic muscles have lower thresholds of electrical stimulation than the small parasympathetic preganglionic fibers innervating the bladder. Intermittent stimulation partially circumvents this problem by utilizing the difference in the relaxation time of the bladder detrusor muscle and the EUS, thereby producing a transient post-stimulus voiding. Such post-stimulus voiding has several drawbacks, however, including short duration (“voiding in spurts”) and elevation of bladder pressure to supra-physiologic levels (with the attendant risk of damage to the upper urinary tract and induction of autonomic dysreflexia). In addition, coincident activation of the leg musculature is a common complaint from patients. In summary, improved neuroprosthetic approaches are urgently required for restoring the bladder control without the drawbacks associated with electrical stimulation of spinal cord. In this project, we propose an alternative minimally-invasive neural stimulation approach based on a focused ultrasonic beam with a novel technology incorporating a SFAT. We propose to study feasibility of providing control of bladder and EUS functions by stimulating the spinal cord with focused ultrasonic beams, a significantly less invasive technology than those dependent on penetrating electrodes. The novel SFAT will be used to stimulate sub-mm-size loci in the spinal cord that are involved in micturition control, with the goal of proof-of-concept efficacy of focused ultrasound therapy for reversal of SCI-induced muscle paralysis. We hypothesize that there exists a range of acoustic intensity (where heat or cavitation generation is negligible) that stimulates spinal cord neurons having no specialized mechanoreceptor properties. The key parameters will be the ultrasound frequency (2-20 MHz), pulse width, pulse repetition frequency, duty cycle, and pulse shape (e.g., short-time pulses within long-time pulses along with varying duty cycles). Additionally, for ac
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710538
Entities
People
- Eun Kim
Organizations
- United States Army
- University of Southern California