Artificial vision by direct optic nerve electrode (AV-DONE) implantation in a blind patient with retinitis pigmentosa

The purpose of this study was to evaluate the efficacy and safety of artificial vision by using a direct optic nerve electrode (AV-DONE) in a blind patient with retinitis pigmentosa (RP). This device, comprising three wire electrodes (0.05 mm in diameter), was implanted into the optic disc of a patient with RP with no light perception vision and the device was left implanted. Six months later, visual sensations were elicited by electrical stimulation through each electrode and the thresholds for the phosphene perception elicited by pulses of 0.25-ms duration/phase and a pulse frequency of 320 Hz were 30, 5, and 70 μA for each electrode. The phosphenes, which ranged in size from that of a match head to an apple, were round, oval, or linear, primarily yellow, and focally distributed. The area of the phosphenes changed when the electrical stimulation was supplied from different electrodes. No complications arose during the follow-up period. Localized visual sensations were produced in a blind patient with advanced RP, suggesting that our system could lead to the development of a useful visual prosthesis system.     

Biocompatibility and durability of Teflon-coated platinum–iridium wires implanted in the vitreous cavity

Teflon-coated platinum–iridium wires are placed in the vitreous as electrodes in artificial vision systems. The purpose of this study was to determine whether these wires have toxicity in the vitreous cavity, and to examine the durability of their coating when grasped by forceps. Rabbits were implanted with platinum–iridium wires that were 50 μm in diameter and coated with Teflon to a total diameter of 68 or 100 μm. To examine the biocompatibility, electroretinograms (ERGs) and fluorescein angiography (FA) were performed before and 1 week, 1, 3, and 6 months after the implantation of the electrode. After 6 months, the eyes were histologically examined with light microscopy. To check the durability, the surface of a coated wire was examined with scanning electron microscopy after grasping with different types of forceps. At all times after the implantation the amplitudes and implicit times of the ERGs recorded were not significantly different from those recorded before the implantation (P > 0.05). FA showed no notable change during the follow-up periods. Histological studies showed that the retinas were intact after 6 months of implantation. There was no damage to the Teflon-coated wire after grasping the wire with forceps with silicon-coated tips, while surface damage of the Teflon that did not extend to the platinum–iridium wire was found when grasped by vitreoretinal forceps. We conclude that Teflon-coated platinum–iridium wire is highly biocompatible in the vitreous for at least 6 months. Wires should be handled with vitreoretinal forceps with silicone-coated tips in order to avoid causing damage during wire manipulation.     

长期置入骶神经根刺激电极的兔组织学变化及其安全性

背景：有研究表明基于阳极阻滞技术的骶神经根刺激器能有效重建脊髓损伤兔的膀胱排尿功能,但符合此技术的刺激电极至今未见报道。 目的：设计并研制既与兔骶神经根匹配又符合阳极阻滞技术的刺激电极,观察长期植入刺激电极的兔骶神经根超微结构及病理形态学变化,评估刺激电极安全性。 方法：纳入新西兰兔30只,随机抽取10只兔切取双侧S2及S3神经前根,光镜下测量其直径后,制成与其直径相匹配的套筒型刺激电极。将剩余20只兔随机分为对照组及植入组,每组10只。植入组麻醉后将刺激电极植入S2及S3神经根前处,饲养半年后处死取材,观察植入处骶神经根超微结构变化。 结果与结论：长期植入该刺激电极后,光学显微镜下见植入组植入处骶神经根神经细胞结构保存良好,轴突无明显变性,无炎症细胞浸润及胶质瘢痕形成;透射电镜下观察,植入组髓鞘排列紧密,无脱髓鞘现象,神经元无核萎缩、核凹陷和异染色质增多等现象。免疫组织化学染色显示,与对照组相比,植入组植入处神经根中胶质纤维酸性蛋白、Bax,Bcl-2和Caspase-3蛋白表达差异无显著性意义。结果说明实验成功研制了兔骶神经根刺激电极,长期植入骶神经根未出现组织病理学改变及无细胞凋亡现象,安全性好。     

Extraction Force and Tissue Change During Removal of a Tined Intramuscular Electrode from Rat Gastrocnemius

Many electrical stimulation protocols employ intramuscular electrodes for the activation of targeted muscles. Electrode displacement from the initial implant site can result in degradation of optimal stimulus parameters. Electrodes with tined tips were developed to reduce electrode migration. In the study reported here, intramuscular electrodes with polypropylene tines at the tip were implanted aseptically in the gastrocnemii of adult rats. Test electrodes were explanted immediately following implant in one group and after periods of 1, 3, 7, 14 and 28 days in others. Force as a function of displacement was recorded during removal of the electrodes. Analysis of the results showed that the electrodes were most vulnerable to movement during the first five days. Between 5 and 7 days after implantation there was significant increase in the force required to dislodge the electrode tip. Histology of muscles from which electrodes had been explanted did not show any increase in the area showing tissue changes as compared to control muscles in which the electrode remained in situ. These results indicated that electrode removal caused disruption of encapsulation tissues, with the surrounding muscle mainly unaffected by the explant process.     

Perioperative Brain Shift and Deep Brain Stimulating Electrode Deformation Analysis: Implications for rigid and non-rigid devices

Deep brain stimulation (DBS) efficacy is related to optimal electrode placement. Several authors have quantified brain shift related to surgical targeting; yet, few reports document and discuss the effects of brain shift after insertion. Objective: To quantify brain shift and electrode displacement after device insertion. Twelve patients were retrospectively reviewed, and one post-operative MRI and one time-delayed CT were obtained for each patient and their implanted electrodes modeled in 3D. Two competing methods were employed to measure the electrode tip location and deviation from the prototypical linear implant after the resolution of acute surgical changes, such as brain shift and pneumocephalus. In the interim between surgery and a pneumocephalus free postoperative scan, electrode deviation was documented in all patients and all electrodes. Significant shift of the electrode tip was identified in rostral, anterior, and medial directions (p < 0.05). Shift was greatest in the rostral direction, measuring an average of 1.41 mm. Brain shift and subsequent electrode displacement occurs in patients after DBS surgery with the reversal of intraoperative brain shift. Rostral displacement is on the order of the height of one DBS contact. Further investigation into the time course of intraoperative brain shift and its potential effects on procedures performed with rigid and non-rigid devices in supine and semi-sitting surgical positions is needed.     

Morphologic and functional evaluation of peripheral nerve fibers regenerated through polyimide sieve electrodes over long-term implantation

We evaluated by morphologic and functional analysis the regeneration of peripheral nerve fibers through polyimide regenerative-type electrodes over long-term implantation. Polyimide sieve electrodes were placed in silicone chambers and implanted between the severed ends of the sciatic nerve in rats. The sieve part had 281 round via holes of 40 microm in diameter, with nine integrated recording-stimulating electrodes arranged around the via holes. The degree of axonal regeneration was examined at 2, 7, and 12 months postimplantation (mpi). Regeneration was successful in 12 of the 13 animals implanted. Reinnervation of distal muscle and nerves increased with time, reaching a plateau about 7 mpi. The number of myelinated fibers increased from 2 to 7 months, at which time it was similar to control values. With time the myelinated fibers matured, with significant increases in axon diameter and myelin thickness. Only 0.6% of the regenerated axons showed evidence of compression near the implanted electrode. The majority of the myelinated fibers that crossed the via holes and had been regenerated through the distal nerve had a normal appearance. Sieve electrodes were useful for nerve stimulation at postimplantation. Stimulation through different active electrodes excited nerve bundles, evoking compound muscle action potentials of varying shape and amplitude, indicative of selective axonal stimulation.     

Simulation of intra-orbital optic nerve electrical stimulation

In blind subjects who still have functional retinal ganglion cells, electrical stimuli applied to the optic nerve can produce localised visual sensations. This has been demonstrated with an intracranially implanted self-sizing spiral cuff electrode, but, to avoid skull opening, intra-orbital cuff implantation is now considered. In its orbital segment, the optic nerve is surrounded by subarachnoidal cerebrospinal fluid (CSF) and dura mater. Dura mater is a tough fibrous tissue that can impede electrical stimulation. In the study, the issue of whether or not to remove the dura mater at the implantation site was addressed using simulation on numerical models. Several volume conductor models were built representing, respectively: the cuff implanted directly around the nerve; the cuff over the nerve after connective tissue encapsulated the implant; and the cuff electrode placed around the dura mater. Stimulation-induced electric potential fields were computed for these configurations using a full 3D finite elements software. Responses of fibres within the nerve were computed. A large range of dural conductivities and several CSF thicknesses were considered. In all simulated conditions, the presence of dura mater around a layer of CSF increased excitation thresholds. Selectivity performance also decreased, but was found to be independent of the CSF thickness. However, simulations showed that, if the diameter of the cuff electrode is adapted to the target nerve, the injected charge associated with activation is limited within a reasonable range. Electrical stimulation of the optic nerve with a cuff electrode implanted around the dura mater should therefore be feasible.     

Long-term implantation of platinum electrodes: Effects on electrode material and nerve tissue

Electrical stimulation of nerves has become an established method in long-term treatment of patients with disturbances in the central or peripheral nervous system. This type of treatment raises questions as to the long-term consequences of implantation in terms of tissue and electrode reactions. The aim of the present study was to find out whether the structure of peripheral nerve tissue is altered after long-term contact with platinum electrodes and the way in which platinum electrodes are changed by prolonged implantation. The study was performed in six dogs which had undergone experiments in which stimulation electrodes were placed bilaterally on the carotid sinus nerves. Fibrotic changes in the nerve bundle and the perineurium were observed after 12·5 years. Accumulation of organic material on the electrode surface was revealed by Auger electron spectroscopy. The surfaces of the implanted electrodes had oxidised and had a high concentration of carbon and measurable amounts of sulphur, indicating corrosion.     

Bioactive anti-inflammatory coating for chronic neural electrodes

Chronic electrodes are widely used for brain degenerative and psychiatric daises such as Parkinson's diseases, major depression, and obsessive-compulsive disorder, and for neuronal prosthesis. Brain immune reaction to electrodes in the form of glial scar encapsulates the electrode and reduces the efficacy of deep brain stimulation and neuronal prosthesis. State-of-the-art strategies for improving brain-electrode interface use passive protein coating to "camouflage" the electrode from the immune system. In this study, we actively reduced the brain immune reaction to the chronic electrodes using immune suppressing protein, that is, interleukin (IL)-1 receptor antagonist. IL-1 receptor antagonist-coated electrodes and noncoated electrodes were chronically implanted in rats. An additional group of rats was chronically implanted with IL-1 receptor antagonist- and laminin-coated electrodes (as passive protein). Examination of glial scaring 1ne and 4 weeks after implantation indicated a significant reduction in the amount of glial scar in the vicinity of the IL-1 receptor antagonist-coated electrode in comparison to both noncoated electrode and laminin-coated electrodes. The results strongly suggest that active immune suppressing protein reduces the level of immune reaction to chronic electrodes already after 1 week after implantation and generates less immune reaction then passive protein coating.     

新型螺旋电极胞外选择性刺激视神经的仿真分析

目的 电刺激中枢神经系统已用于治疗一些神经病、精神病和感觉障碍.尽管在一些应用里相当成功,但现有的刺激技术不能精确地控制激活靶向神经元.提出一种形状自适应的新型螺旋电极,实现选择性刺激视神经.方法 应用COMSOL Multiphysics建立视神经和新型螺旋电极的几何模型；新型电极由起支撑和绝缘隔离作用的硅橡胶螺旋支架和嵌入支架内的铂金触点组成.引入激活函数来表征刺激效果,应用COMSOL仿真分析新型螺旋电极对视神经纤维选择性刺激的能力,并考虑电极触点位置的变化对选择性的影响.结果 假定激活函数的归一化阈值为0.1 V/m2,新型螺旋电极和传统袖套电极激活函数大于阈值的比例差异仅为1.2410％.当新型螺旋电极两端的电极触点靠近中间触点时,可以先激活细视神经纤维束,后激活粗纤维束.结论 仿真结果表明新型螺旋电极可以达到传统袖套电极的刺激效果.改变新型螺旋电极的触点位置可以实现选择性激活视神经纤维束.     

Acute and chronic implantation of coiled wire intraneural electrodes during cyclical electrical stimulation

The posterior tibial nerves of 18 rabbits were intraneurally implanted with coiled wire electrodes for up to 9 weeks to evaluate their usefulness for neuromuscular electrical stimulation. In one group an electrode was implanted and removed in one leg while the other leg was chronically implanted. A second group was chronically implanted without electrical stimulation in one leg and implanted with cyclical electrical stimulation applied through the electrode in the other leg. No significant changes in nerve conduction velocities between the time of implantation and up to 9 weeks post-implantation were observed in either the stimulated or the non-stimulated nerves. Little change in motor current threshold was observed beyond 10 days postimplantation. The nerves showed little or no histologic demyelination or denervation in most specimens, although in about 40% of the nerves, a bulbous formation of connective tissue was observed at electrode entry and exit sites with some demyelination in these regions. The spinal cords showed no histologic abnormalities in either group. The gastrocenemius and soleus muscles showed only occasional signs of denervation. One cat was implanted in both the posterior tibial and peroneal nerves of each leg for a 4-year period. Threshold current showed very little change during the implantation period. The nerves showed minimal focal demyelination at the electrode site and the muscles showed normal fibers.     

Selective stimulation of cat sciatic nerve using an array of varying-length microelectrodes

Restoration of motor function to individuals who have had spinal cord injuries or stroke has been hampered by the lack of an interface to the peripheral nervous system. A suitable interface should provide selective stimulation of a large number of individual muscle groups with graded recruitment of force. We have developed a new neural interface, the Utah Slanted Electrode Array (USEA), that was designed to be implanted into peripheral nerves. Its goal is to provide such an interface that could be useful in rehabilitation as well as neuroscience applications. In this study, the stimulation capabilities of the USEA were evaluated in acute experiments in cat sciatic nerve. The recruitment properties and the selectivity of stimulation were examined by determining the target muscles excited by stimulation via each of the 100 electrodes in the array and using force transducers to record the force produced in these muscles. It is shown in the results that groups of up to 15 electrodes were inserted into individual fascicles. Stimulation slightly above threshold was selective to one muscle group for most individual electrodes. At higher currents, co-activation of agonist but not antagonist muscles was observed in some instances. Recruitment curves for the electrode array were broader with twitch thresholds starting at much lower currents than for cuff electrodes. In these experiments, it is also shown that certain combinations of electrode pairs, inserted into an individual fascicle, excite fiber populations with substantial overlap, whereas other pairs appear to address independent populations. We conclude that the USEA permits more selective stimulation at much lower current intensities with more graded recruitment of individual muscles than is achieved by conventional cuff electrodes.     

An intrafascicular electrode for recording of action potentials in peripheral nerves

We are developing a new type of bipolar recording electrode intended for implantation within individual fascicles of mammalian peripheral nerves. In the experiments reported here we used electrodes fabricated from 25 μm diameter Pt wire, 50 μm 90% Pt-10% Ir wire and 7 μm carbon fibers. The electrodes were implanted in the sciatic nerves of rats and in the ulnar nerves of cats. The signal-to-noise ratio of recorded activity induced by nonnoxious mechanical stimulation of the skin and joints was studied as a function of the type of electrode material used, the amount of insulation removed from the recording zone, and the longitudinal separation of the recording zones of bipolar electrode pairs. Both acute and short term (two day) chronic experiments were performed. The results indicate that a bipolar electrode made from Teflon^™-insulated, 25 μm diameter, 90% Pt-10% Ir wire, having a 1–2 mm long recording zone, can be used for recording of peripheral nerve activity when implanted with one wire inside the fascicle and the other lead level with the first lead, but outside the fascicle. No insulating cuff needs to be placed around the nerve trunk.     

Enhancement of Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Devices

Insufficient nutrient supply has been suggested to be one of the etiologies for intervertebral disc (IVD) degeneration. We are investigating nutrient transport into the IVD as a potential treatment strategy for disc degeneration. Most cellular activities in the IVD (e.g., cell proliferation and extracellular matrix production) are mainly driven by adenosine-5′-triphosphate (ATP) which is the main energy currency. The objective of this study was to investigate the effect of increased mass transfer on ATP production in the IVD by the implantation of polyurethane (PU) mass transfer devices. In this study, the porcine functional spine units were used and divided into intact, device and surgical groups. For the device and surgical groups, two puncture holes were created bilaterally at the dorsal side of the annulus fibrosus (AF) region and the PU mass transfer devices were only implanted into the holes in the device group. Surgical groups were observed for the effects of placing the holes through the AF only. After 7 days of culture, the surgical group exhibited a significant reduction in the compressive stiffness and disc height compared to the intact and device groups, whereas no significant differences were found in compressive stiffness, disc height and cell viability between the intact and device groups. ATP, lactate and the proteoglycan contents in the device group were significantly higher than the intact group. These results indicated that the implantation of the PU mass transfer device can promote the nutrient transport and enhance energy production without compromising mechanical and cellular functions in the disc. These results also suggested that compromise to the AF has a negative impact on the IVD and must be addressed when treatment strategies are considered. The results of this study will help guide the development of potential strategies for disc degeneration.     

Development of sutureless vascular connecting system for easy implantation of small-caliber artificial grafts

A novel sutureless vascular connecting system, an assembly with a delivery rod, an introducing sheath, and a connecting device, was developed for easy implantation of small-caliber vascular grafts less than 2 mm in internal diameter. A microporous stainless tube (length 2 mm, external diameter 1.6 mm, wall thickness 65 µm, pore diameter 400 µm, pore-to-pore distance 500 µm) was designed to serve as a connecting device. The feasibility of the system was tested using two types of preliminary animal experiments. One animal model consisted of graft implantation into the rat abdominal aorta (1.5 mm in diameter). The connecting device was inserted into the proximal and distal ends of the aorta through the introducing sheath by pushing the delivery rod with the connecting device placed over it. Subsequently, the aortic segments were inserted into both ends of model grafts made of segmented polyurethane (1.8 mm in internal diameter) and were fixed with banding silk threads from the exterior. The procedure was completed within 20 min without requiring specialized microsurgery techniques. Blood leakage and obstruction did not occur. The second model consisted of an end-to-end anastomosis between rabbit common carotid arteries (2 mm in diameter), which was performed within several minutes of blood flow interruption. Scanning electron microscopy demonstrated that the luminal surface of the device was fully covered with endothelial cells (ECs) after 1 week as a result of transluminal ingrowth of native ECs through the micropores in the device. This endothelialization may prevent early thrombus-induced occlusion. This simple and “easy-to-learn” technique will promote the development of small-caliber arterial grafts, and furthermore, it may have potential for clinical application.     

A novel carbon fiber implantation assembly for cerebral voltammetric measurements in freely moving rats

In vivo voltammetry has been widely employed to monitor the effects of drugs on dopamine metabolism. In the present study, we report on the use of a newly designed assembly for implantation of carbon fiber microelectrodes for voltammetric measurements in freely moving animals. The assembly consists of an electrode holder and a fixed support (implanted stereotaxically) which is cemented to the rat skull. The working carbon fiber electrode is cemented to the electrode holder, and can be lowered into the fixed support for implantation into the brain parenchyma. This implantation assembly has been used to study the effects of tail-pinch on dopamine metabolism (extracellular DOPAC levels) in the nucleus accumbens and ventral tegmental area of the awake rat. Using this implantation assembly and 3 carbon fiber electrodes, oxidation peaks for ascorbic acid (-100 mV) and DOPAC (+ 100 mV) were recorded in both brain structures. Mild tail pressure for 7 min led to an increase in extracellular DOPAC levels in the nucleus accumbens. A smaller increase was observed in the ventral tegmental area. The DOPAC signals remained elevated for some time after removal of the stressor. This implantation assembly represents a convenient system for implanting carbon fiber electrodes in the freely moving rat, which can be employed to investigate the effects of behavioral manipulation on dopaminergic neurons at the terminal as well as at the cell body level. This microdevice could also be usefully employed for other in vivo electrochemical studies.     

A new technique for implanting a fine-wire microelectrode for chronic recording of unit activity from freely-moving mice

We report here a newly developed chronic implantation technique using an epoxy-coated fine-stainless steel wire (33 microm in diameter) to record single unit activity from the brain of freely-moving mice with as little tissue injury as possible. Since the fine-wire electrode is not capable of staying straight by itself or of penetrating into the brain, a pair of permanent neodymium magnets placed on a micromanipulator as well as below the animal's head was used for stereotaxic implantation to keep the fine-wire straight and strong by the magnetic fields. With those implanted electrodes recording of single units from the hippocampal CA1 of freely-moving mice was performed during sleep and wakefulness.     

A percutaneous electrode for long-term monitoring of bio-electrical signals in humans

Solid percutaneous electrodes made of vitreous carbon were inserted surgically in the forearm of human subjects. The electrodes were left in the arm for several months without any particular care or protection. Evaluation of the electrodes shows good appearance, good mechanical stability, excellent ability of picking up bioelectrical signals and low interface impedance between electrode and tissue. Histological examination shows growth of epidermis around the electrode. No signs of chronic inflammation or foreign body giant cell formation was found.     

Translational development and pre-clinical evaluation of prototype gastrointestinal mock-up devices: only robotic placement of plastic?

Abstract

Background: The aim of this study was to address the vision of wireless theranostic devices distributed along the gastrointestinal (GI) tract by defining design requirements, developing prototype mock-ups, and establishing a minimally invasive surgical approach for the implantation process.

Methods: Questionnaires for contextual analysis and use case scenarios addressing the technical issues of an implantable GI device, a possible scenario for implantation, preparation and calibration of a device, and therapeutic usage by professionals and patients were completed and discussed by an interdisciplinary team of surgeons, engineers, and product designers. Two acute porcine experiments were conducted with a robotic surgical system under general anaesthesia.

Results: A variety of requirements for the design and implantation of implantable devices for modulating GI motility were defined. Five prototype implant mock-ups were three-dimensional (3D)-printed from black polymer material (width 22.32?mm, height 7.66?mm) and successfully implanted on the stomach, duodenum, jejunum, ileum, and colon using the robotic surgical system, without any complications.

Conclusions: Our study shows the development and successful pre-clinical evaluation of a reliable device design with a minimally invasive implantation approach. Several stages of device development, including pre-clinical tests, characterisation of clinical requirements, regulatory affairs, and marketing issues should be managed side by side.     

Fabrication and evaluation of conductive elastomer electrodes for neural stimulation

This study explored the feasibility of applying nanocomposites derived from conducting organic polymers and silicone elastomers to fabricate electrodes for neural stimulation. A novel combination of nanoparticulate polypyrrole polymerized within a processable elastomeric silicone host polymer was evaluated in vitro and in vivo. The electrical properties of the elastomeric conductors were strongly dependent on their composition, and mixtures were identified that provided high and stable conductivity. Methods were developed for incorporating conductive polymer-siloxane co-polymer nanocomposite and silicone insulating polymers into thin-layered structures for simple single-poled electrode fabrication. In vitro testing revealed that the materials were stable under continuous pulsing for at least 10 days. Single contact prototype nerve cuff electrodes were fabricated and device functionality was demonstrated in vivo following acute implantation. The results of this study demonstrate the feasibility of conductive elastomers for peripheral nerve stimulating electrodes. Matching the mechanical properties of cuff electrode to those of the underlying neural tissue is expected to improve the long-term tissue response to the presence of the electrode.