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. 2017 Aug;14(4):046020.
doi: 10.1088/1741-2552/aa7586.

Evaluation of focused multipolar stimulation for cochlear implants: a preclinical safety study

Robert K Shepherd  1 , Andrew K Wise, Ya Lang Enke, Paul M Carter, James B Fallon
Affiliations

Evaluation of focused multipolar stimulation for cochlear implants: a preclinical safety study

Robert K Shepherd et al. J Neural Eng. 2017 Aug.

Abstract

Objective: Cochlear implants (CIs) have a limited number of independent stimulation channels due to the highly conductive nature of the fluid-filled cochlea. Attempts to develop highly focused stimulation to improve speech perception in CI users includes the use of simultaneous stimulation via multiple current sources. Focused multipolar (FMP) stimulation is an example of this approach and has been shown to reduce interaction between stimulating channels. However, compared with conventional biphasic current pulses generated from a single current source, FMP is a complex stimulus that includes extended periods of stimulation before charge recovery is achieved, raising questions on whether chronic stimulation with this strategy is safe. The present study evaluated the long-term safety of intracochlear stimulation using FMP in a preclinical animal model of profound deafness.

Approach: Six cats were bilaterally implanted with scala tympani electrode arrays two months after deafening, and received continuous unilateral FMP stimulation at levels that evoked a behavioural response for periods of up to 182 d. Electrode impedance, electrically-evoked compound action potentials (ECAPs) and auditory brainstem responses (EABRs) were monitored periodically over the course of the stimulation program from both the stimulated and contralateral control cochleae. On completion of the stimulation program cochleae were examined histologically and the electrode arrays were evaluated for evidence of platinum (Pt) corrosion.

Main results: There was no significant difference in electrode impedance between control and chronically stimulated electrodes following long-term FMP stimulation. Moreover, there was no significant difference between ECAP and EABR thresholds evoked from control or stimulated cochleae at either the onset of stimulation or at completion of the stimulation program. Chronic FMP stimulation had no effect on spiral ganglion neuron (SGN) survival when compared with unstimulated control cochleae. Long-term implantation typically evoked a mild foreign body reaction proximal to the electrode array; however stimulated cochleae exhibited a small but statistically significant increase in the tissue response. Finally, there was no evidence of Pt corrosion following long-term FMP stimulation; stimulated electrodes exhibited the same surface features as the unstimulated control electrodes.

Significance: Chronic intracochlear FMP stimulation at levels used in the present study did not adversely affect electrically-evoked neural thresholds or SGN survival but evoked a small, benign increase in inflammatory response compared to control ears. Moreover chronic FMP stimulation does not affect the surface of Pt electrodes at suprathreshold stimulus levels. These findings support the safe clinical application of an FMP stimulation strategy.

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Figures

Figure 1
Figure 1
(a) Schematic diagram of the Hybrid L-14 electrode array used in this study. The electrode array contains 14 Pt electrodes on a silicone carrier. The array tapered from 0.35 mm wide at electrode 14 to 0.5 mm at electrode 1. All dimensions are in mm. (b) Plane x-ray of a left cat cochlea implanted with a Hybrid L electrode array. This array can be inserted into the upper basal turn allowing 14 electrodes to be located within the cochlea. Electrode E1 (arrow) is located at the round window.
Figure 2
Figure 2
The stimulus used was designed to represent a ‘worst case’ scenario in terms of charge recovery time and degree of focusing using FMP stimulation. The left panel represents the stimulus waveforms to be delivered to specified channels and is comprised of 4 biphasic pulse trains on non-adjacent FMP channels. Note that these waveforms represent the positions of focused channels that will be delivered to the neural elements, not the current delivered to each electrode. The middle panel represents the currents to be delivered to specified electrodes. The currents are calculated based on the sum of all the channel waveforms (left panel) transformed into appropriate electrode currents as described in the text. They are designed to achieve maximal focusing of each channel. The right panel represents the net charge delivered to each electrode. Unlike the very rapid charge recovery associated with a conventional biphasic current pulse delivered sequentially, complete charge recovery using FMP stimulation was not ensured until the end of the 8 ms stimulus frame when all electrodes were shorted for 100 μs. The 8 ms stimulus was then repeated in a continuous loop.
Figure 3
Figure 3
Electrode impedance (mean + SEM) of both the chronically stimulated and control electrodes recorded at the completion of each animal’s stimulation program. The impedance of the chronically stimulated electrodes showed no significant difference to that of the controls (2-Way ANOVA, electrode (p > 0.55), side (p > 0.60), electrode × side (p = 0.898), n =6).
Figure 4
Figure 4
Representative ECAP waveforms recorded from the left (stimulated) cochlea of FMP4 at the (a) initial and (b) final recording following 182 days of electrical stimulation. Both set of responses were evoked by stimulation from electrode 6. Stimulus level is given in CL (bold = threshold). In this example there is a slight decrease (15 CLs) in threshold over the course of the stimulation program. Vertical bar = 150 μV; horizontal bar = 1 ms.
Figure 5
Figure 5
Mean ECAP thresholds (+ SEM) for all electrodes recorded at (a) the outset (Initial) and (b) on completion (Final) of the chronic stimulation program. There was no significant difference between the sides at either time point (2-Way ANOVAs (Electrode (p < 0.001), Side (p > 0.1), n=6)).
Figure 6
Figure 6
Representative photomicrographs illustrating the upper basal (UB), upper middle (UM) and apical (A) turns of (a) the control and (b) the stimulated cochlea of animal FMP4. The cochleae in this example were implanted for a period of 210 days and the left cochlea (b) stimulated for 182 days. Tissue response to the chronically implanted electrode array is evident in the basal turn of the stimulated cochlea (* illustrates the location of the electrode array). There was no tissue response in the control cochlea (a). (c) and (d) are photomicrographs from the stimulated and control cochlea respectively of animal FMP6. The cochleae in this example were implanted for a period of 201 days and the right cochlea (c) stimulated for 173 days. Tissue response to the chronically implanted electrode array is evident in the basal turn of both the stimulated and control cochleae (* in (c) and (d)). All animals in this cohort exhibited widespread hair cell and organ of Corti loss (arrowhead; for clarity illustrated in (d) only). Extensive loss of SGNs (arrow; for clarity illustrated in (a) only) occurred in the basal and middle turns of both cohorts; near normal SGN survival was apparent in the apical turn. The Hybrid L14 electrode arrays were inserted into the upper basal turn, reflecting the tissue response in this region of all stimulated and some control cochleae. There was no evidence of a tissue response distal to the electrode array. Scale bar = 200 μm.
Figure 7
Figure 7
Representative photomicrographs illustrating the SGNs in Rosenthal’s canal in the apical (A), upper middle (UM) and upper basal (UB) turns of the four cochleae illustrated in Figure 6. (a) control and (b) stimulated cochlea of FMP4; (c) stimulated and (d) control cochlea of FMP6. The extensive loss of SGNs observed in both the basal and middle turns of all cochleae is a feature of both the deafening technique and the extended duration of deafness associated with the present study. Chronic FMP stimulation was restricted to the basal turn; importantly we observed no difference in the SGN population in this cochlear region when comparing stimulated versus control cochleae. Scale bar = 100 μm
Figure 8
Figure 8
Mean SGN density for the five cochlear regions examined for both stimulated and unstimulated control cochleae. 2-Way RM ANOVA demonstrated a highly statistically significant effect of cochlear region (p < 0.001; n=6) typical of the “U” shaped distribution of SGN survival associated with this deafening technique. There was no significant difference in SGN density between stimulated and control cochleae (p > 0.1). LB, lower basal; UB, upper basal; LM, lower middle; UM, upper middle; A, apical.
Figure 9
Figure 9
Photomicrograph of the upper basal turn of stimulated cochlea FMP4 illustrating the typical tissue response to chronic cochlear implantation and electrical stimulation using the FMP strategy; control cochleae typically exhibited a reduced tissue response. In this example the tissue response consisted of a thin mature fibrous tissue capsule (arrowheads) surrounding the electrode array (e), with some loose areolar tissue and some chronic inflammatory cells (*; monocytes and macrophages) scattered within the scala tympani outside the electrode-tissue capsule. Evidence of angiogenesis associated with the tissue response was apparent (arrow). Scale bar = 100 μm.
Figure 10
Figure 10
The extent of tissue response in the scala tympani expressed as a percentage of the scala tympani cross sectional area for both chronically implanted control and stimulated cochleae (n=6). Chronic electrical stimulation evoked a small but significant increase in fibrous tissue in a region of the cochlea associated with the electrode array 2-Way RM ANOVA (Cochlear region and Treatment (Stimulated Vs Unstimulated) with a significant main effect of treatment Stimulated > Unstimulated (p=0.034). Post-hoc UB Stimulated > UB Unstimulated (p=0.004; Holm Sidak). Significant main effect of region with UB significantly different to LB and LM in the Stimulated cohort (p=0.009; Holm Sidak). There were no interactions. LB = lower basal; UB = upper basal; LM = lower middle. (* p < 0.05).
Figure 11
Figure 11
Representative SEM micrographs from control and stimulated electrodes used in this study. (a) Low power micrograph of E9 from control electrode array of FMP4. This electrode was implanted for 182 days but not electrically stimulated. Although there is abundant score marks associated with the manufacture of the array there was no evidence of Pt corrosion. Pt, platinum electrode; S, silicone. (b) Higher-power image from (a) (box) showing the sharp score marks associated with the manufacturing process without evidence of Pt corrosion. This electrode was graded 0. (c) Micrograph of E8 from the chronically stimulated electrode array of FMP4 following 182 days of stimulation. Electrodes E6–E10 were the most activated electrodes on the array using the FMP stimulation strategy. While sharp score marks associated with manufacture were present there was no evidence of Pt corrosion. This electrode was graded 0. (d) SEM micrograph of E6 from chronically stimulated electrode array of FMP1 following 167 days of stimulation. In addition to the sharp score marks associated with manufacture, the Pt surface showed evidence of some cellular debris consistent with the tissue response observed in this cochlea. There was no evidence of corrosion. This electrode was graded 1. (a) scale bar = 100 μm; (b–d); scale bar = 25 μm.
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