Simulation of epiretinal prostheses - evaluation of geometrical factors affecting stimulation thresholds.

BACKGROUND: An accurate understanding of the electrical interaction between retinal prostheses and retinal tissue is important to design effective devices. Previous studies have used modelling approaches to simulate electric fields generated by epiretinal prostheses in saline and to simulate retinal ganglion cell (RGC) activation using passive or/and active biophysical models of the retina. These models have limited scope for studying an implanted human retinal prosthesis as they often do not account for real geometry and composition of the prosthesis-retina interface. This interface consists of real dimensions and location of stimulation and ground electrodes that are separated by the retinal tissue and surrounded by physiological fluids. METHODS: In this study, we combined the prosthesis-retina interface elements into a framework to evaluate the geometrical factors affecting stimulation thresholds for epiretinal prostheses used in clinical human trials, as described by Balthasar et al. in their Investigative Ophthalmology and Visual Science (IOVS) paper published in 2008 using the Argus I epiretinal implants. Finite element method (FEM) based computations were used to estimate threshold currents based on a threshold criterion employing a passive electric model of the retina. RESULTS: Threshold currents and impedances were estimated for different electrode-retina distances. The profiles and the values for thresholds and impedances obtained from our simulation framework are within the range of measured values in the only elaborate published clinical trial until now using Argus I epiretinal implants. An estimation of resolution for the electrodes used in these trials was provided. Our results reiterate the importance of close proximity between electrodes and retina for safe and efficient retinal stimulation. CONCLUSIONS: The validation of our simulation framework being relevant for epiretinal prosthesis research is derived from the good agreement of the computed trends and values of the current study with measurements demonstrated in existing clinical trials on humans (Argus I). The proposed simulation framework could be used to generate the relationship between threshold and impedance for any electrode geometry and consequently be an effective tool for design engineers, surgeons and electrophysiologists.

Poststroke upper-limb rehabilitation using 5 to 7 inserted microstimulators: implant procedure, safety, and efficacy for restoration of function.

OBJECTIVE: To investigate the feasibility of implanting microstimulators to deliver programmed nerve stimulation for sequenced muscle activation to recover arm-hand functions. DESIGN: By using a minimally invasive procedure and local anesthesia, 5 to 7 microstimulators can be safely and comfortably implanted adjacent to targeted radial nerve branches in the arm and forearm of 7 subjects with poststroke paresis. The microstimulators' position should remain stable with no tissue infection and can be programmed to produce effective personalized functional muscle activity with no discomfort for a preliminary 12-week study. Clinical testing, before and after the study, is reported in the accompanying study. SETTING: Microstimulator implantations in a sterile operating room. PARTICIPANTS: Seven adults, with poststroke hemiparesis of 12 months or more. INTERVENTION: Under local anesthesia, a stimulating probe was inserted to identify radial nerve branches. Microstimulators were inserted by using an introducer and were retrievable for 6 days by attached suture. Each device was powered via a radiofrequency link from 2 external cuff coils connected to a control unit. MAIN OUTCOME MEASURES: To achieve low threshold values at the target sites with minimal implant discomfort. Microstimulators and external equipment were monitored over 12 weeks of exercise. RESULTS: Seven subjects were implanted with 41 microstimulators, 5 to 7 per subject, taking 3.5 to 6 hours. Implantation pain levels were 20% more than anticipated. No infections or microstimulator failures occurred. Mean nerve thresholds ranged between 4.0 to 7.7 microcoulomb/cm(2)/phase over 90 days, indicating that cathodes were within 2 to 4 mm of target sites. In 1 subject, 2 additional microstimulators were inserted. CONCLUSIONS: Microstimulators were safely implanted with no infection or failure. The system was reliable and programmed effectively to perform exercises at home for functional restoration.

Therapeutic effectiveness of electric stimulation of the upper-limb poststroke using implanted microstimulators.

OBJECTIVE: To investigate the therapeutic effect of functional exercise augmented by programmable implanted microstimulators on arm and hand function. DESIGN: Before and after study. SETTING: Implantation was performed in a neurosurgery unit, systems were programmed, and tests were conducted in a university laboratory and subjects exercised at home. PARTICIPANTS: Hemiparetic subjects (N=7) with reduced upper-limb function who were at least 12 months poststroke were recruited from the community. No subjects withdrew. INTERVENTION: Microstimulators were implanted into the arms and forearms to activate elbow, wrist, and finger extension, and thumb abduction. After training and programming of the system, subjects underwent 12 weeks of functional home-based exercise with stimulation. MAIN OUTCOME MEASURES: The primary functional measure was the Action Research Arm Test (ARAT). Impairment measures included upper-limb Fugl-Meyer Assessment (FMA) and tests of motor control (tracking index), spasticity (electromyography stretch index) strength, and active range of motion (AROM). The assessor was not blinded, but scores were validated by an independent blinded observer. RESULTS: All subjects were able to perform functional activities at home by using the system. Compliance was excellent, and there were no serious adverse events. Statistically significant improvements were measured (P<.05) in the tracking index (57.3 degrees(2)+/-48.65 degrees(2)), FMA score (6.3+/-3.59), wrist-extensor strength (5.5+/-4.37 N), and wrist AROM (19.3 degrees +/-18.96 degrees). The mean improvement in ARAT score +/- SD of 4.9+/-7.89 was not statistically significant. CONCLUSIONS: This study has shown the feasibility of a programmable implanted microstimulator system used at home to perform functional exercises and a reduction in impairment after 12 weeks.

Acoustic to electric pitch comparisons in cochlear implant subjects with residual hearing.

The aim of this study was to assess the frequency-position function resulting from electric stimulation of electrodes in cochlear implant subjects with significant residual hearing in their nonimplanted ear. Six cochlear implant users compared the pitch of the auditory sensation produced by stimulation of an intracochlear electrode to the pitch of acoustic pure tones presented to their contralateral nonimplanted ear. Subjects were implanted with different Clarion electrode arrays, designed to lie close to the inner wall of the cochlea. High-resolution radiographs were used to determine the electrode positions in the cochlea. Four out of six subjects presented electrode insertions deeper than 450 degrees . We used a two-interval (one acoustic, one electric), two-alternative forced choice protocol (2I-2AFC), asking the subject to indicate which stimulus sounded the highest in pitch. Pure tones were used as acoustic stimuli. Electric stimuli consisted of trains of biphasic pulses presented at relatively high rates [higher than 700 pulses per second (pps)]. First, all electric stimuli were balanced in loudness across electrodes. Second, acoustic pure tones, chosen to approximate roughly the pitch sensation produced by each electrode, were balanced in loudness to electric stimuli. When electrode insertion lengths were used to describe electrode positions, the pitch sensations produced by electric stimulation were found to be more than two octaves lower than predicted by Greenwood's frequency-position function. When insertion angles were used to describe electrode positions, the pitch sensations were found about one octave lower than the frequency-position function of a normal ear. The difference found between both descriptions is because of the fact that these electrode arrays were designed to lie close to the modiolus. As a consequence, the site of excitation produced at the level of the organ of Corti corresponds to a longer length than the electrode insertion length, which is used in Greenwood's function. Although exact measurements of the round window position as well as the length of the cochlea could explain the remaining one octave difference found when insertion angles were used, physiological phenomena (e.g., stimulation of the spiral ganglion cells) could also create this difference. From these data, analysis filters could be determined in sound coding strategies to match the pitch percepts elicited by electrode stimulation. This step might be of main importance for music perception and for the fitting of bilateral cochlear implants.

Electrical stimulation using implantable radiofrequency microstimulators to relieve pain associated with shoulder subluxation in chronic hemiplegic stroke.

Objective. To evaluate the ability to relieve shoulder pain by implanting ceramic-case versions of radiofrequency microstimulators (RFM) in paralyzed shoulder muscles. Materials and Methods. A 66-year-old man, who had left-sided chronic hemiplegia due to a stroke five years previously, had developed shoulder subluxation resulting in pain. Two RFM devices were implanted, one next to the axillary nerve and one at the motor point of the middle deltoid muscle. Electrical stimulation at both sites was commenced two weeks after implantation for a six-month period. Our evaluation of the effectiveness of the RFM devices has been by measuring pain (using the visual analog scale: VAS), range of motion at the shoulder, strength of the deltoid muscle, degree of shoulder subluxation, and muscle atrophy. Following commencement of stimulation, follow-up evaluations were performed at one, two, three, four, and six weeks, three and six months, and after six months of no stimulation. Results. During the treatment period of six months of stimulation, the patient's pain had reduced from 70 to 0 on the VAS. At six months after completion of the treatment, pain relief and effective evoked muscle contraction have remained. Conclusion. Although these results suggest that the feasibility of using RFM devices implanted both epineurally to the axillary nerve and next to the muscle motor point in this one patient, to relieve pain and elicit contraction, further investigation is needed to demonstrate the clinical feasibility of using RFMs for treating poststroke shoulder pain.

A preliminary feasibility study of different implantable pulse generators technologies for diaphragm pacing system.

Diaphragm pacing stimulation (DPS) for ventilator-dependent patients provides several advantages over conventional techniques such as phrenic nerve pacing or mechanical ventilator support. To date, the only existing system for DPS uses lead electrodes, percutaneously attached to an external pulse generator (PG). However, for a widespread use of this technique it would be more appropriate to eliminate the need for percutaneous wire and use a totally implantable system. The aim of this study was to determine if it were feasible to replace the external PG by an implantable system. We present here the results of a preliminary study of two different PG, currently used in other electrical stimulation (ES) clinical applications, which could be used as implantable DPS systems. One radio-frequency-powered PG, one rechargeable battery-powered PG, and the current external PG were tested. Each was attached to the externalized part of the wires, connected to the diaphragm and tidal volume (TV) was measured in one ventilator-dependent patient who has been using the current percutaneous stimulator for 3 years. Results indicated that both implantable PGs could achieve equivalent ventilatory requirements to the current external stimulator. No significant differences were observed between the three PG systems when stimulating the electrodes as used in the patient's own chronically attached PG system. We found that TV increased with increases in charge and frequency as expected when stimulating the patient's electrodes individually and in combination with each PG system. These results are a significant step toward developing a totally implantable DPS system for the ventilator-dependant patients. Further clinical tests to demonstrate the safety and efficacy of a fully implanted DPS system are warranted.

Implantable microstimulator: magnetic resonance safety at 1.5 Tesla.

RATIONALE AND OBJECTIVE: Ex vivo testing is necessary to characterize implants to determine if it is safe for the patient to undergo a magnetic resonance imaging (MRI) examination. Therefore, the objective of this study was to evaluate MR safety for an implantable microstimulator in association with a 1.5 Tesla MR system. METHODS: A microstimulator (RF BION, Alfred E. Mann Foundation for Scientific Research, Valencia, CA) was evaluated for magnetic field interactions and MRI-related heating. The functional aspects of this implant were assessed immediately before and after exposure to MRI (15 different pulse sequences). Artifacts were also characterized. RESULTS: Magnetic field interactions exhibited by the microstimulator will not pose a hazard after a suitable postimplantation period has elapsed. Temperature changes will not pose a risk. The function of the microstimulator was unaffected by MRI. Artifacts will only create a problem if the area of interest is in proximity to this implant (largest artifact area: T1-weighted spin echo, 2291 mm2; gradient echo, 3310 mm2). CONCLUSION: The overall findings indicated that it is safe for a patient with the microstimulator to undergo MRI at 1.5 Tesla by following specific safety guidelines described herein.

Functional MRI of auditory cortex activated by multisite electrical stimulation of the cochlea.

Electrical stimulation of the ear of deaf patients via cochlear implants offers a unique occasion to study activity of central auditory pathways with fMRI, without bias due to scanner noise. Such measurements, however, require one to control the possible interference between fMRI acquisition and the implanted electrodes. A series of measurements on a customized phantom designed to characterize the level of induced currents during MRI acquisition is presented. These experiments demonstrate that the major artifactual contribution is due to radiofrequency interaction and that safe experimental conditions can be obtained with proper shielding of the stimulation cables. The induced currents could be reduced to low levels (<50 microA for a duration <2 ms), below the acoustic perceptual threshold of cochlear implant subjects. Subsequent fMRI experiments on a patient using an Ineraid cochlear implant were conducted. Results revealed bilateral localized activation of the primary auditory cortex. Stimulation of two different intracochlear electrodes elicited activity in two neighboring, but different, regions, in agreement with the known tonotopical organization of the auditory cortex. This work paves the way for fMRI studies of a broad selection of auditory paradigms without interference from unwanted noise.