Electrical Stimulation of Vocal Fold Adduction Triggered by Laryngeal Electromyography Using a Custom Implant.

PURPOSE: Medialization procedures for unilateral vocal fold (VF) paralysis generally improve voice but do not fully replace dynamic VF adduction. Paralyzed VFs typically experience synkinetic reinnervation, which makes it feasible to elicit movement through electrical stimulation. We tested a novel laryngeal pacing implant capable of providing closed-loop (automatic) stimulation of a VF triggered by electromyography (EMG) potentials from the contralateral VF. METHOD: A custom, battery-powered, microprocessor-based stimulator was tested in eight dogs with bipolar electrodes implanted for recording EMG from the left VF and stimulating adduction of the right VF. A cuff electrode on the left recurrent laryngeal nerve (RLN) stimulated unilateral VF adduction, modeling voluntary control in anesthetized animals. Closed-loop stimulation was tested in both acute and chronic experiments. Synkinetic reinnervation was created in two animals by right RLN transection and suture repair to model unilateral VF paralysis. RESULTS: In all animals, left VF activation through RLN stimulation generated a robust EMG response that rapidly triggered stimulation of contralateral thyroarytenoid and lateral cricoarytenoid muscles, causing nearly simultaneous bilateral adduction. Optimal triggering of VF stimulation from elicited EMG was achieved using independent onset and offset thresholds. Real-time artifact blanking allowed closed-loop stimulation without self-perpetuating feedback, despite the proximity of recording and stimulation electrodes. CONCLUSIONS: Using a custom implant system, we demonstrated real-time closed-loop stimulation of one VF triggered by the activation of the contralateral VF. This approach could potentially restore dynamic glottic closure for reflexive behaviors or phonation in cases of unilateral VF paralysis with synkinetic reinnervation. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24492133.

Development of a Closed-Loop Stimulator for Laryngeal Reanimation, Part 1: Devices.

OBJECTIVE:: The goal of this work was to create implantable stimulator systems that could be used in animal experiments on laryngeal paralysis, including "closed-loop" stimulation of impaired muscles triggered by electromyographic (EMG) potentials from healthy muscles. STUDY DESIGN:: Iterative device design and testing. METHODS:: A series of microcontroller-based implantable devices were built that incorporated increasingly sophisticated features for stimulation, EMG recording, and communication across the skin. Specific engineering challenges included minimizing power consumption, achieving charge-balanced and relatively high stimulation capacity, implementing noninvasive communication across the skin, providing real-time processing of EMG signals, and mitigating effects of shock artifacts. Bench testing was used to verify performance. RESULTS:: Two prototypes are described in detail. Each system is based on an "implant" and an external "communication adapter" that interfaces both with the implant and with external computers for adjustments and monitoring. The first version described is inductively powered and referred to as the "inductive laryngeal stimulator." It uses inductive coupling for both power and communication and performs EMG processing in the communication adapter module. The second version, a "battery-powered laryngeal stimulator," consists of an autonomous battery-powered implant with onboard EMG processing and artifact control; it communicates by infrared light with the external communication adapter for setup and monitoring. CONCLUSIONS:: The devices met design and performance specifications and have proved useful in the animal experiments that are described in Part 2 of this series. Detailed descriptions of the circuits and their firmware are made available in the Appendix. Level of Evidence: NA.

Development of a Closed-Loop Stimulator for Laryngeal Reanimation: Part 2. Device Testing in the Canine Model of Laryngeal Paralysis.

OBJECTIVE:: Laryngeal paralysis of central or peripheral origin can potentially be treated using functional electrical stimulation (FES) of laryngeal muscles. Experiments in canines (dogs) were performed using implant prototypes capable of closed-loop FES to refine engineering designs and specifications, test surgical approaches for implantation, and better understand the in vivo effects of laryngeal muscle stimulation on short- and long-term glottic function. STUDY DESIGN:: Prospective, laboratory. METHODS:: We designed and tested a series of microprocessor-based implantable devices that can stimulate glottic opening or closing based on input from physiological control signals (real-time processing of electromyographic [EMG] signals). After acute device testing experiments, 2 dogs were implanted for 8 and 24 months, with periodic testing of closed-loop laryngeal muscle stimulation triggered from EMG signals. In total, 5 dogs were tested for the effects of laryngeal muscle stimulation on vocal fold (VF) posturing in larynges with nerve supplies that were intact (7 VFs), synkinetically reinnervated (2 VFs), or chronically denervated (1 VF). In 3 cases, the stimulation was combined with airflow-driven phonation to study the consequent modulation of phonatory parameters. RESULTS:: Initial device prototypes used inductive coupling for power and communication, while later iterations used battery power and infrared light communication (detailed descriptions are provided in the Part 1 companion paper). Two animals were successfully implanted with the inductively powered units, which operated until removed at 8 months in 1 animal or for more than 16 months in the second animal. Surgically, the encapsulated implants were well tolerated, and procedures for placing, attaching, and connecting the devices were developed. To simulate EMG control signals in anesthetized animals, we created 2 types of nerve/muscle signal sources. In one approach, a neck muscle had a cuff electrode placed on its motor nerve that was connected to transdermal electrical connection ports for periodic testing. In the second approach, the recurrent laryngeal nerve on one side of the larynx was stimulated to generate a VF EMG signal, which was then used to trigger FES of the paralyzed contralateral side (eg, restoring VF movement symmetry). Implant testing identified effective stimulation parameters and closed-loop stimulation artifact rejection techniques for FES of both healthy and paralyzed VFs. Stimulation levels effective for VF adduction did not cause signs of discomfort during awake testing. CONCLUSION:: Our inductive and battery-powered prototypes performed effectively during in vivo testing, and the 2 units that were implanted for long-term evaluation held up well. As a proof of concept, we demonstrated that elicited neck strap muscle or laryngeal EMG potentials could be used as a control signal for closed-loop stimulation of laryngeal adduction and vocal pitch modulation, depending on electrode positioning, and that VFs were stimulable in the presence of synkinetic reinnervation or chronic denervation.

Design of a visible-light spectroscopy clinical tissue oximeter.

We develop a clinical visible-light spectroscopy (VLS) tissue oximeter. Unlike currently approved near-infrared spectroscopy (NIRS) or pulse oximetry (SpO2%), VLS relies on locally absorbed, shallow-penetrating visible light (475 to 625 nm) for the monitoring of microvascular hemoglobin oxygen saturation (StO2%), allowing incorporation into therapeutic catheters and probes. A range of probes is developed, including noncontact wands, invasive catheters, and penetrating needles with injection ports. Data are collected from: 1. probes, standards, and reference solutions to optimize each component; 2. ex vivo hemoglobin solutions analyzed for StO2% and pO2 during deoxygenation; and 3. human subject skin and mucosal tissue surfaces. Results show that differential VLS allows extraction of features and minimization of scattering effects, in vitro VLS oximetry reproduces the expected sigmoid hemoglobin binding curve, and in vivo VLS spectroscopy of human tissue allows for real-time monitoring (e.g., gastrointestinal mucosal saturation 69+/-4%, n=804; gastrointestinal tumor saturation 45+/-23%, n=14; and p<0.0001), with reproducible values and small standard deviations (SDs) in normal tissues. FDA approved VLS systems began shipping earlier this year. We conclude that VLS is suitable for the real-time collection of spectroscopic and oximetric data from human tissues, and that a VLS oximeter has application to the monitoring of localized subsurface hemoglobin oxygen saturation in the microvascular tissue spaces of human subjects.

Front-tracking image reconstruction algorithm for EIT-monitored cryosurgery using the boundary element method.

The effectiveness of cryosurgery, treatment of tumors by freezing, is highly dependent on knowledge of transient freezing extent, and therefore relies heavily on real-time imaging techniques for monitoring. Electrical impedance tomography (EIT) holds much promise for this application. In cryosurgery there is a three order of magnitude change in impedance across the freezing boundary and there is a priori knowledge of the freezing origin. Furthermore, an EIT image of the tissue can be done prior to the cryosurgery. In this study, we have developed an EIT front tracking reconstruction algorithm which takes advantage of these particular attributes of cryosurgery. The method tracks the freezing interface rather than the impedance distribution in the freezing tissue. In addition to drastically reducing the number of parameters needed to define the image, the computational complexity is further reduced by using the more appropriate boundary element method (BEM) for solution to the forward problem. The front-tracking method was found to converge rapidly and accurately to a variety of simulated phantom images.

Electrical impedance tomography for imaging tissue electroporation.

Electroporation is a method to introduce molecules, such as gene constructs or small drugs, into cells by temporarily permeating the cell membrane with electric pulses. In molecular medicine and biotechnology, tissue electroporation is performed with electrodes placed in the target area of the body. Currently, tissue electroporation, as with all other methods of molecular medicine, is performed without real-time control or near-term information regarding the extent and degree of electroporation. This paper expands the work from our previous study by implementing new ex vivo experimental data with "front-tracking" analysis for the image reconstruction algorithm. The experimental data is incorporated into numerical simulations of electroporation procedures and images are generated using the new reconstruction algorithm to demonstrate that electrical impedance tomography (EIT) can produce an image of the electroporated area. Combining EIT with electroporation could become an important biotechnological and medical technique to introduce therapeutic molecules into cells in tissue at predetermined areas of the body.

Distributed network imaging and electrical impedance tomography of minimally invasive surgery.

Minimally invasive surgery has become highly dependent on imaging. For instance, the effectiveness of cryosurgery in treating cancer is dependent on knowledge of freezing extent, and relies on real-time imaging techniques for monitoring. However, medical imaging is often very expensive and therefore not available to most of the world population. Here we propose the concept of distributed network imaging (DNI) which could make medical imaging and minimally invasive surgery available to all who need these advanced medical modalities. We demonstrate the concept through electrical impedance tomography (EIT) of cryosurgery. The central idea is to develop an inexpensive measurend (data collection hardware) at a remote site and then to connect the measurend apparatus to an advanced image reconstruction server, which can serve a large number of distributed measurends at remote sites, using existing communication conduits (Ethernet, telephone, satellite, etc.). These conduits transfer the raw data from the measurend to the server and the reconstructed image from the server to the measurend. Electrical impedance tomography (EIT) is an imaging modality which utilizes tissue impedance variation to construct an image. The EIT measurend which consists of electrodes, a power supply, and means to measure voltage is inexpensive, and therefore suitable for DNI. EIT is also very well-suited to imaging cryosurgery since frozen tissue impedance is much higher than that of unfrozen tissue. In this study, we first develop numerical models to illustrate the theoretical ability of EIT to image cryosurgery. We begin with a simplified two dimensional model, and then extend the study to the more appropriate three dimensional model. Our simulated finite element phantoms and pixel-based Newton-Raphson reconstruction algorithms were able to produce easily identifiable images of frozen regions within tissue. Then, we demonstrate the feasibility of the DNI concept though a case study using EIT to image an in vitro liver cryosurgery procedure through a modem. We find that the acquired raw data packets are less than 5KB per image and the images, using compression, do not exceed 50KB per image.

A feasibility study for electrical impedance tomography as a means to monitor tissue electroporation for molecular medicine.

Molecular medicine involves the introduction of macromolecules, such as drugs or gene constructs, into specific cells of the body. Electroporation, which uses electric pulses to permeate cell membranes, is a method for achieving this. However, as with other molecular medicine procedures, it lacks a real-time mechanism to detect and control which cells have been affected. We propose and demonstrate, via computer simulation, that electrical impedance tomography has the potential for detecting and imaging electroporation of cells in tissue in real-time, thereby providing feedback for controlling electroporation.