The use of hydrogel as an electrode-skin interface for electrode array FES applications

Functional electrical stimulation is commonly used to restore function in post-stroke patients in upper and lower limb applications. Location of the electrodes can be a problem hence some research groups have begun to experiment with electrode arrays. Electrode arrays are interfaced with a thin continuous hydrogel sheet which is high resistivity to reduce transverse currents between electrodes in the array. Research using electrode arrays has all been conducted in a laboratory environment over short time periods but it is suspected that this approach will not be feasible over longer time periods due to changes in hydrogel resistivity.High resistivity hydrogel samples were tested by leaving them in contact with the skin over a seven day period. The samples became extremely conductive with resistivities reaching around 10–50 Ω m. The effect of these resistivity changes was studied using finite element analysis to solve for the stationary current quasi-static electric field gradient in the tissue. Electrical stimulation efficiency and focality were calculated for both a high and low resistivity electrode–skin interface layer at different tissue depths. The results showed that low resistivity hydrogel produced significant decreases in stimulation efficiency and focality compared to high resistivity hydrogel.     

3D-nanostructured boron-doped diamond for microelectrode array neural interfacing

The electrode material is a key element in the design of long-term neural implants and neuroprostheses. To date, the ideal electrode material offering high longevity, biocompatibility, low-noise recording and high stimulation capabilities remains to be found. We show that 3D-nanostructured boron doped diamond (BDD), an innovative material consisting in a chemically stable material with a high aspect ratio structure obtained by encapsulation of a carbon nanotube template within two BDD nanolayers, allows neural cell attachment, survival and neurite extension. Further, we developed arrays of 20-μm-diameter 3D-nanostructured BDD microelectrodes for neural interfacing. These microelectrodes exhibited low impedances and low intrinsic recording noise levels. In particular, they allowed the detection of low amplitude (10–20 μV) local-field potentials, single units and multiunit bursts neural activity in both acute whole embryonic hindbrain-spinal cord preparations and long-term hippocampal cell cultures. Also, cyclic voltammetry measurements showed a wide potential window of about 3 V and a charge storage capacity of 10 mC.cm⁻², showing high potentiality of this material for neural stimulation. These results demonstrate the attractiveness of 3D-nanostructured BDD as a novel material for neural interfacing, with potential applications for the design of biocompatible neural implants for the exploration and rehabilitation of the nervous system.     

An all-diamond,hermetic electrical feedthrough array for a retinal prosthesis

The interface between medical implants and the human nervous system is rapidly becoming more and more complex. This rise in complexity is driving the need for increasing numbers of densely packed electrical feedthrough to carry signals to and from implanted devices. This is particularly crucial in the field of neural prosthesis where high resolution stimulating or recording arrays near peripheral nerves or in the brain could dramatically improve the performance of these devices. Here we describe a flexible strategy for implementing high density, high count arrays of hermetic electrical feedthroughs by forming conducting nitrogen doped nanocrystalline diamond channels within an insulating polycrystalline diamond substrate. A unique feature of these arrays is that the feedthroughs can themselves be used as stimulating electrodes for neural tissue. Our particular application is such a feedthrough, designed as a component of a retinal implant to restore vision to the blind. The hermeticity of the feedthroughs means that the array can also form part of an implantable capsule which can interface directly with internal electronic chips. The hermeticity of the array is demonstrated by helium leak tests and electrical and electrochemical characterisation of the feedthroughs is described. The nitrogen doped nanocrystalline diamond forming the electrical feedthroughs is shown to be non-cyctotoxic. New fabrication strategies, such as the one described here, combined with the exceptional biostability of diamond can be exploited to generate a range of biomedical implants that last for the lifetime of the user without fear of degradation.     

A multi-channel stimulator and electrode array providing a rotating current whirlpool for electrical stimulation of wounds

When electrical stimulation is used on wounds, the electrical current has difficulty penetrating areas where there is necrotic tissue. Further, for an irregularly shaped wound, current distribution is poor in some areas of the wound since conventional two-electrode delivery systems provide the greatest current in a line directly between the electrodes. A new stimulator and electrode system is described which uses three electrodes spaced around a wound to disperse current more evenly. The stimulator senses tissue impedance and then redirects current by altering its Thevenin's output impedance for each electrode; each of the three electrodes becomes the active one in sequence while the remaining are the sink electrodes. Eight subjects were examined to test the stimulator. Electrical stimulation was applied to the skin above the quadriceps muscle at currents of 15 mA in six subjects without wounds and in two subjects with wounds. The relationship between electrode position and current dispersion on the skin was examined with a two-electrode vs. a three-electrode system to set stimulation parameters for the computer. The results showed that the three-electrode system could (1) detect areas of the skin with high impedance; (2) compensate by altering the Thevenin's output impedance at each of the three electrodes to shift current to high impedance areas; (3) provide uniform current across the skin as assessed by skin current and blood flow measurements with a laser Doppler flow imager.     

Operational challenges of retinal prostheses

Two computational models for research on retinal implants are presented. In the first model, the electric field produced by a multi-electrode array in a uniform retina is calculated. It is shown how cross talk of activated electrodes and the resulting bunching of field lines in monopole and dipole activation prevent high resolution imaging with retinal implants. Furthermore, it is demonstrated how sequential stimulation and multipolar stimulation may overcome this limitation. In the second model a target volume, i.e., a probe cylinder approximating a bipolar cell, in the retina is chosen, and the passive Heaviside cable equation is solved inside this target volume to calculate the depolarization of the cell membrane. The depolarization as a function of time indicates that shorter signals stimulate better as long as the current does not change sign during stimulation of the retina, i.e., mono-phasic stimulation. Both computational models are equally applicable to epiretinal, subretinal, and suprachoroidal vision implants.     

An electrode array that minimizes blood loss for radiofrequency-assisted hepatic resection

Hepatic resection is currently the standard treatment for liver cancer. During hepatic resection part of the liver containing the tumor is surgically removed. This type of surgery is accompanied by high blood loss of 0.6–1.35 L. Blood loss is associated with increased complication rates, prolonged hospital stay, and reduced patient survival, especially when transfusion is required. Other researchers have suggested using radiofrequency (rf) or microwave ablation to coagulate a tissue slice before resection to reduce blood loss, but conventional devices typically take several hours. We developed a device consisting of a linear array of blade-shaped, 1 cm wide radiofrequency (rf) electrodes 1.5 cm apart. Bipolar rf power is applied between pairs of adjacent electrodes, leading to high tissue temperatures between the electrodes that promote coagulation of large vessels (>3 mm) in the resection plane. Rapid switching of applied power between pairs of adjacent electrodes allows simultaneous heating and coagulation of the entire resection plane within 3–6 min. In seven in vivo trials in a porcine model, resection along a plane pre-coagulated with the device resulted in little (<20 mL) to no blood loss, while coagulating all vessels (up to 4.5 mm diameter in this study). Average treatment time (from placement of the device to transection) was 6.8 ± 0.5 min when four electrodes were used, and 11.3 ± 1.2 min when 5–7 electrodes were used. This device may reduce blood loss related morbidity during resection and reduce treatment time by coagulating all vessels in the resection plane.     

Short-term biological safety of a photoelectric dye used as a component of retinal prostheses

We have designed a new type of retinal prosthesis with a photoelectric dye that transfers photon energy to generate electric potentials. The purpose of this study was to test the safety of a photoelectric dye, 2-[2-[4-(dibutylami no)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide (NK-5962), used for retinal prostheses. The retinal cells, derived from chick neurosensory retinas at the 12-day embryonic stage, were a mixed population of retinal neurons and glial cells, and were cultured for 2 days either under protection from light or under continuous light exposure at 230 lux for 9 h daily in the presence of the photoelectric dye at varying concentrations (1.6 × 10⁻⁵, 1.6 × 10⁻⁶, and 1.6 × 10⁻⁷ M) to assess cell viability by staining live cells and dead cells. Dispersed retinal pigment epithelial cells at the same embryonic stage were incubated with the photoelectric dye at varying concentrations (6.6 × 10⁻⁵, 6.6 × 10⁻⁶, and 6.6 × 10⁻⁷ M) for 4 h under protection from light or under continuous light exposure at 320 lux to assess cytotoxicity by measuring the activity of lactate dehydrogenase leaking from cells. The majority of retinal cells were alive with only a small percentage of dead cells under the dark condition or the light condition in the presence or the absence of the photoelectric dye. The percentage of dead cells was significantly smaller at higher concentrations of the photoelectric dye (P = 0.0183, two-factor analysis of variance), while the percentage of dead cells was not significantly different between the dark condition and the light condition (P = 0.3102). Percent cytotoxicity values were negative, indicating protective effects in all groups of retinal pigment epithelial cells incubated with varying concentrations of the photoelectric dye. The photoelectric dye showed no cytotoxicity to chick retinal cells or retinal pigment epithelial cells on short-term exposure. In addition, this photoelectric dye might have protective effects on both types of cells.     

Simulation of a phosphene-based visual field: Visual acuity in a pixelized vision system

A visual prosthesis for the blind using electrical stimulation of the visual cortex will require the development of an array of electrodes. Passage of current through these electrodes is expected to create a visual image made up of a matrix of discrete phosphenes. The quality of the visual sense thus provided will be a function of many parameters, particularly the number of electrodes and their spacing. We are conducting a series of psychophysical experiments with a portable “phosphene” simulator to obtain estimates of suitable values for electrode number and spacing. The simulator consists of a small video camera and monitor worn by a normally sighted human subject. To simulate a discrete phosphene field, the monitor is masked by an opaque perforated film. The visual angle subtended by images from the masked monitor is 1.7° or less, depending on the mask, and falls within the fovea of the subject. In the study presented here, we measured visual acuity as a function of the number of pixels and their spacing in the mask. Visual acuity was inversely proportional to pixel density, and trained subjects could achieve about 20/26 visual acuity with a 1024 pixel image. We conclude that 625 electrodes implanted in a 1 cm by 1 cm area near the foveal representation of the visual cortex should produce a phosphene image with a visual acuity of approximately 20/30. Such an acuity could provide useful restoration of functional vision for the profoundly blind.     

Theory and design of capacitor electrodes for chronic stimulation

Conventional metal electrodes generate electrochemical byproducts during stimulation of nerve or muscle. These byproducts may cause tissue damage, especially with the long-term stimulation necessary with neural prosthetic devices. To prevent the possibility of such damage, completely insulated electrodes have been devised which deliver current pulses by capacitive charging of the electrode surface, not involving electrochemical reactions. Anodised discs of porous tantalum, 1·0 mm in diameter and 0·25 mm thick, can deliver 0·5 ms, 5 mA pulses. Such electrodes are available as components of commercial capacitors and are easily adapted for biological use. The design may be optimised by mathematical analysis of an equivalent electrical circuit.In vitro tests demonstrate a clear advantage of these electrodes over capacitively coupled platinum-iridium electrodes in preventing oxidation-reduction reactions. The electrodes are stable on chronic implantation and should provide a safer interface between neural prosthetic devices and human tissue.     

Glial reaction to photoelectric dye-based retinal prostheses implanted in the subretinal space of rats

We have designed a new type of retinal prosthesis using polyethylene films coupled with photoelectric dye molecules that absorb light and convert photon energy to electric potentials. An extruded-blown film of high-density polyethylene was used as the original polyethylene film. Recrystallized film was made by recrystallization from the melting of the original polyethylene film. A photoelectric dye,2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the two types of polyethylene films through amide linkages. Samples of the original dye-coupled film, the dye-coupled recrystallized film, and the dye-uncoupled plain film were implanted in the subretinal space of normal adult rats. Frozen sections were cut from the eyes enucleated at 1 week or 1 month and were either stained with hematoxylin and eosin, stained immunohistochemically for glial fibrillary acidic protein (GFAP), or processed for in situ apoptosis detection. The results revealed that retinal tissue damage was negligible with no inflammatory cells and few apoptotic cells. GFAP was significantly up-regulated in retinal sites with the implantation of all types of polyethylene films at 1 week, compared with the adjacent retinal sites (P < 0.005, analysis of variance). The GFAP up-regulation was also present at 1 month for the plain film and dye-coupled recrystallized film (P < 0.05). Glial cell encirclement around the films increased significantly between 1 week and 1 month (P = 0.023, two-factor analysis of variance) but was not significantly different among the three types of polyethylene films (P = 0.4531). These results showed evidence of glial reactions to the photoelectric dye-coupled polyethylene films implanted into the subretinal space of rat eyes and also proved their basic biological safety.     

Biomechanical characterization of a low density silicone elastomer filled with hollow microspheres for maxillofacial prostheses

An ideal material for maxillofacial prostheses has not been found. We created a novel material: silicone elastomer filled with hollow microspheres and characterized its biomechanical properties. Expancel hollow microspheres were mixed with MDX4-4210 silicone elastomer using Q7-9180 silicone fluid as diluent. The volume fractions of microspheres were 0, 5, 15, and 30%?v/v (volume ratio to the total volume of MDX4-4210 and microspheres). The microspheres dispersed well in the matrix. The physical properties and biocompatibility of the composites were examined. Shock absorption was the greatest by the 5%?v/v composite, and decreased with increasing concentrations of microspheres. The density, thermal conductivity, Shore A hardness, tear and tensile strength decreased with increasing concentrations of microspheres, while elongation at break increased. Importantly, the tear strength of all composites was markedly lower than that of pure silicone elastomer. Cell viability assays indicated that the composite was of good biocompatibility. The composite with a volume fraction of 5% exhibited the optimal properties for use as a maxillofacial prosthesis, though its tear strength was markedly lower than that of silicone elastomer. In conclusion, we developed a novel light and soft material with good flexibility and biocompatibility, which holds a promising prospect for clinical application as maxillofacial prosthesis.     

Technique for rapid,permanent documentation of intracerebral electrode sites

Formalin fixed brains are blocked and frozen in 20% polyethylene glycol 6000. The blocks are oriented and 50 to 150 μ thick sections are cut to expose electrode tracts. An appropriate unstained section is mounted in glycerol-saline on a slide. The section is obliquely transilluminated from below and photographed on Polaroid film using a camera fitted with an extension bellows and macro lens. The total time required to obtain a permanent record of a selected section is less than five minutes. No darkroom facilities are required.     

Optimum electrode geometry for spinal cord stimulation: The narrow bipole and tripole

A computer model is used to calculate the optimum geometry of an epidural electrode, consisting of a longitudinal contact array, for spinal cord stimulation in the managmment of chronic, intractable pain. 3D models of the spinal area are used for the computation of stimulation induced fields, and a cable model of myelinated nerve fibre is used for the calculation of the threshold stimulus to excite large dorsal column and dorsal root fibres. The criteria for the geometry of the longitudinal contact array are: a low threshold for the stimulation of dorsal column fibres compared with dorsal root fibres; and a low stimulation voltage (and current). For both percutaneous and laminectomy electrodes, the contact length should be approximately 1.5 mm, and the optimum contact separation, as determined by the computer model, is 2–2.5 mm. The contacts for a laminectomy electrode should be approximately 4 mm wide. This electrode geometry is applicable to all spinal levels where the dorsal columns can be stimulated (C1-2 down to L1). The stimulating electrode should preferably be used as a tripole with one (central) cathode.     

Best estimation of spectrum profiles for diagnosing femoral prostheses loosening

For the past few years, some authors have proposed several vibration analysis techniques to detect the prosthetic femoral stem loosening, having found some differences in the frequency response between secure and loose stems. Classical methods like periodogram have been used in most studies for the spectral estimation, and their conclusions have been reached only by visual inspection. A new metric called Non-linear Logarithmic Weighted Distance (NLWD), based on log-spectral distance is presented. As its name suggests, the spectral power is weighted in order to highlight discriminatory patterns of the spectral profiles. A Generalized Discriminant Ratio (GDR) based on NLWD metric has been also defined. In this study, experiments on a cadaveric dried bone with two kinds of fixation, Loose Stem class (LS) and Secure Stem class (SS), have been analyzed. To select the most discriminating approach to spectral estimation, five well known algorithms (Welch's, Burg's Auto-Regressive (AR), Auto-Regressive Moving Average (ARMA), Multiple Signal Classification (MUSIC) and Thomson's Multi-taper (MTM)) have been compared by using GDR. Finally, the use of the MTM method is proposed for the analysis of bone–stem interface vibratory signals, since it yields the most discriminatory profiles.     

Calculations of temperature rise produced in body tissue by a spherical electrode

Two estimates of temperature rise produced in body tissue when a spherical electrode passes current have been calculated. The estimates bracket the expected temperature rise. Time-transient and steady-state results have been obtained. The effects of heat transfer through the highly conductive metal electrode and irreversible. Faradaic reactions have been considered. The calculations indicate that electrodes smaller than about 2 μm in radius produce a peak temperature rise of about 1°C when driven by typical square current pulses of 25 μA intensity and 200 μs duration. The results are presented in a graphic form allowing for quick estimation of the expected peak temperature rise around electrodes of a specific radius, which are driven with a pulse of known current density and duration.     

Anatomic basis of the liver for the development of a perihepatic prosthesis

We studied specimens from 50 cadavers (27 men and 23 women) to obtain anatomical data concerning the liver and its attachments. The results allowed us to develop a polyglactin perihepatic prosthesis for compression of the injured liver. The falciform ligament and a narrowing of the hepatic parenchyma at this level allow attachment of the prosthesis. Separate prostheses were designed for each lobe. Clinical use has demonstrated that our prosthesis can be used to achieve effective control of haemorrhage and bile leakage.

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Etude anatomique du foie. Développement d'une prothèse péri-hépatique

Résumé Sur une série de 50 pièces anatomiques d'adultes (27 hommes, 23 femmes), l'étude morphométrique du foie, de ses attaches dorsales et leurs variations a permis la confection d'une prothèse périhépatique en polyglactine adaptable à chaque lobe et fixée grâce à des artifices anatomiques. Celle-ci assure une compression efficace du parenchyme lésé et donc une hémostase et une bilistase correctes. Le ligament falciforme et le rétrecissement du parenchyme hépatique à son niveau assurent le maintien de la prothèse. Un exemplaire a été réalisé pour chaque lobe.

     

The degeneration of biological cardiovascular prostheses under pro-calcific metabolic conditions in a small animal model

In order to allow for a comparative evaluation of the in vivo degeneration of biological and tissue-engineered heart valves and vascular grafts, a small animal model of accelerated cardiovascular calcification is desired. Wistar rats (n = 102; 6 groups) were fed ad libitum with regular chow and 5 different regimens of pro-calcific diet supplemented with combinations of vitamin D (VD), cholesterol (CH) and dicalcium phosphate (PH). Moreover, cryopreserved (n = 7) or detergent-decellularized rat aortic conduit grafts (n = 6) were infrarenally implanted in Wistar rats under severely pro-calcific conditions. The follow-up lasted up to 12 weeks. High-dose application of VD (300,000 IU/kg), CH (2%) and PH (1.5%) resulted in elevated serum calcium and cholesterol levels as well as LDL/HDL ratio. It increased the tissue MMP activity visualized by in situ zymography and caused significantly aggravated calcification of the native aortic valve as well as the aortic wall as assessed by histology and micro-computed tomography. (Immuno)histology and quantitative real-time PCR revealed chondro-osteogenic cell transformation, lipid deposition, nitrosative stress and low-level inflammation to be involved in the formation of calcific lesions. Despite pro-calcific in vivo conditions, decellularization significantly reduced calcification, inflammation and intimal hyperplasia in aortic conduit implants. A well balanced dietary trigger for pathologic metabolic conditions may represent an appropriate mid-term treatment to induce calcifying degeneration of aortic valves as well as vascular structures in the systemic circulation in rats. With respect to experimental investigation focusing on calcifying degeneration of native or prosthetic tissue, this regimen may serve as a valuable tool with a rapid onset and multi-facetted character of cardiovascular degeneration.     

A speech treatment algorithm based on a programmable filter bank for cochlear prostheses

In this article, a programmable stimulation algorithm developed for cochlear prostheses has been described. The algorithm was based on a speech treatment system with programmable filter-bank modeling which allowed flexible speech signal processing. With its digital system, it could be adapted to any cochlear prosthetic apparatus driven by a Digital Signal Processor (DSP). The different bands of the digital filters used in the speech-processing of this stimulation algorithm were fully programmable, and could be adjusted to the patient's pathology. This provided clinicians with the possibility of dividing up the frequency band to adapt the filtering according to the patient's audiogram and different pre- and post-operative tests. To generate stimuli in the nerve endings of the cochlea, the proposed algorithm allows the speech signal energy to be extracted by the filter bank (f1, f2, …, fN), coding of the output information to be made, and the appropriate commands to be transmitted to the internal part of the cochlea via the prosthetic modulator. In fact, the speech-signal energy (E1, E2,…, EN) extracted during the processing phase serves to estimate the stimulating pulse parameters transmitted to the inner ear (cochlea) through the implanted micro-stimulator. An IBM compatible personal computer (PC) is connected to the external part of the prosthesis to allow clinical assessments and adjustments to be made of the different parameters, especially during the first clinical experiments. On the other hand, this algorithm was developed to generate a real-time display showing the affected frequency bands as well as their relative stimulation levels. This can assist patients during the rehabilitation phase by providing a visual reference. Hence, with this visual tool, clinicians are able to carry out therapeutic experiments during the rehabilitation phase, correctly adjust the operational parameters of the hearing device, and assess the electrical charges to be injected into the cochlear biological tissue (current pulse levels). The software provided in this stimulation algorithm ensures flexibility in programming, ease of use, and different safety features that can help to satisfactorily meet individual needs.     

Usefulness of polyurethane for small-caliber vascular prostheses in comparison with autologous vein graft

 For long-term patency of small-caliber vascular prostheses, antithrombogenicity and microporous structure are very important. We have developed a new technique to give a microporous structure to a polyurethane vascular prosthesis that has favorable antithrombogenicity. A solution of tetrahydrofuran/dimethylformamide (1 : 1) containing 13 wt% of segmented polyurethane (PTMG + MDI) and calcium carbonate (mean particle size, 8 μm) was dipcoated on a glass mandrel 3 mm in diameter and placed into distilled water. After the glass mandrel was removed, the polyurethane tube was placed into hydrochloric acid, and a microporous polyurethane vascular prosthesis was produced. Prostheses made in this fashion, and autologous jugular vein grafts were implanted into the femoral artery and the carotid artery of mongrel dogs. Patency was recognized on the arteriogram and duplex scanning (ultrasonography), and the removed grafts were inspected macroscopically and microscopically. This prosthesis was similar in elasticity to a vein graft. Patency was defined 8 weeks after implantation, and this prosthesis showed less intimal hyperplasia than the autologous vein graft. The new polyurethane prosthesis might be useful for small-caliber vascular reconstruction. Received: December 18, 2000 / Accepted: January 28, 2002