Radio-frequency induced heating of intra-cranial EEG electrodes: The more the colder?

Many neurological disorders are analyzed and treated with implantable electrodes. Many patients with such electrodes have to undergo MRI examinations - often unrelated to their implant - at the risk of radio-frequency induced heating. The number of electrode contact sites of these implants keeps increasing due to improvements in manufacturing and computational algorithms. Electrode grids with multiple receive channels couple to the RF fields present in MRI, but, due to their proximity, a combination of leads has a coupling response which is not a superposition of the individual leads' response. To investigate the problem of RF-induced heating of coupled multi-lead implants, temperature mapping was performed on a set of intra-cranial electroencephalogram (icEEG) electrode grid prototypes with increasing number of contact sites (1-16). Additionally, electric field measurements were used to investigate the radio-frequency heating characteristics of the implants in different media combinations, simulating the device being partially immersed inside the patient. MR measurements show RF-induced heating up to 19.6 K for the single electrode, reducing monotonically with larger number of contact sites to a minimum of 0.9 K for the largest grid. The SAR calculated from temperature measurements agrees well with electric field mapping: The same trend is visible for different insertion lengths, however, the energy dissipated by the whole implant varies with the grid size and insertion length. Thus, in the tested circumstances, a larger electrode number either reduced or had a similar risk of RF induced heating, indicating, that the size of electrode grids is a design parameter, which can be used to change an implants RF response and in turn to reduce the risk of RF induced heating and improve the safety of patient with neuro-implants undergoing MRI examinations.

It's the little things: On the complexity of planar electrode heating in MRI.

Neurological disorders are increasingly analysed and treated with implantable electrodes, and patients with such electrodes are studied with MRI despite the risk of radio-frequency (RF) induced heating during the MRI exam. Recent clinical research suggests that electrodes with smaller diameters of the electrical interface between implant and tissue are beneficial; however, the influence of this electrode contact diameter on RF-induced heating has not been investigated. In this work, electrode contact diameters between 0.3 and 4 mm of implantable electrodes appropriate for stimulation and electrocorticography were evaluated in a 1.5 T MRI system. In situ temperature measurements adapted from the ASTM standard test method were performed and complemented by simulations of the specific absorption rate (SAR) to assess local SAR values, temperature increase and the distribution of dissipated power. Measurements showed temperature changes between 0.8 K and 53 K for different electrode contact diameters, which is well above the legal limit of 1 K. Systematic errors in the temperature measurements are to be expected, as the temperature sensors may disturb the heating pattern near small electrodes. Compared to large electrodes, simulations suggest that small electrodes are subject to less dissipated power, but more localized power density. Thus, smaller electrodes might be classified as safe in current certification procedures but may be more likely to burn adjacent tissue. To assess these local heating phenomena, smaller temperature sensors or new non-invasive temperature sensing methods are needed.

On the stability of poly-ethylenedioxythiopene as coating material for active neural implants.

This article deals with the stability of poly-ethylenedioxythiopene (PEDOT) coatings under high loads of current pulses. Test parameters were chosen to match many peripheral nervous system applications in regard of charge injection, pulse width, and repetition frequency. PEDOT coatings were characterized with electrochemical impedance spectroscopes and pulse tests. After 60-100 million pulses, impedance increased and a more capacitive behavior was observed. A mean-time-to-failure of 127 million pulses could be calculated, suggesting a stable coating for at least this time frame with superior properties in regard of conventional platinum electrodes.

The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms": current progress, challenges, and charting the future.

There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.

Fabrication and validation of reference structures for the localization of subdural standard- and micro-electrodes in MRI.

OBJECTIVE: Report simple reference structure fabrication and validate the precise localization of subdural micro- and standard electrodes in magnetic resonance imaging (MRI) in phantom experiments. APPROACH: Electrode contacts with diameters of 0.3 mm and 4 mm are localized in 1.5 T MRI using reference structures made of silicone and iron oxide nanoparticle doping. The precision of the localization procedure was assessed for several standard MRI sequences and implant orientations in phantom experiments and compared to common clinical localization procedures. MAIN RESULTS: A localization precision of 0.41 ± 0.20 mm could be achieved for both electrode diameters compared to 1.46 ± 0.69 mm that was achieved for 4 mm standard electrode contacts localized using a common clinical standard method. The new reference structures are intrinsically bio-compatible, and they can be detected with currently available feature detection software so that a clinical implementation of this technology should be feasible. SIGNIFICANCE: Neuropathologies are increasingly diagnosed and treated with subdural electrodes, where the exact localization of the electrode contacts with respect to the patient's cortical anatomy is a prerequisite for the procedure. Post-implantation electrode localization using MRI may be advantageous compared to the common alternative of CT-MRI image co-registration, as it avoids systematic localization errors associated with the co-registration itself, as well as brain shift and implant movement. Additionally, MRI provides superior soft tissue contrast for the identification of brain lesions without exposing the patient to ionizing radiation. Recent studies show that smaller electrodes and high-density electrode grids are ideal for clinical and research purposes, but the localization of these devices in MRI has not been demonstrated.

Electrical connectors for neural implants: design, state of the art and future challenges of an underestimated component.

Technological advances in electrically active implantable devices have increased the complexity of hardware design. In particular, the increasing number of stimulation and recording channels requires innovative approaches for connectors that interface electrodes with the implant circuitry. OBJECTIVE: This work aims to provide a common theoretical ground for implantable connector development with a focus on neural applications. APPROACH: Aspects and experiences from several disciplines are compiled from an engineering perspective to discuss the state of the art of connector solutions. Whenever available, we also present general design guidelines. MAIN RESULTS: Degradation mechanisms, material stability and design rules in terms of biocompatibility and biostability are introduced. Considering contact physics, we address the design and characterization of the contact zone and review contaminants, wear and contact degradation. For high-channel counts and body-like environments, insulation can be even more crucial than the electrical connection itself. Therefore, we also introduce the requirements for electrical insulation to prevent signal loss and distortion and discuss its impact on the practical implementation. SIGNIFICANCE: A final review is dedicated to the state of the art connector concepts, their mechanical setup, electrical performance and the interface to other implant components. We conclude with an outlook for possible approaches for the future generations of implants.

A voltage-controlled current source with regulated electrode bias-voltage for safe neural stimulation.

A current source for neural stimulation is presented which converts arbitrary voltage signals to current-controlled signals while regulating the offset-voltage across the stimulation electrodes in order to keep the electrodes in an electrochemical state that allows for injecting a maximum charge. The offset-voltage can either be set to 0V or to a bias-voltage, e.g. of a few 100mV, as it can be advantageous for fully exploiting the charge injection capacity of iridium oxide electrodes.

Matrix-addressable, active electrode arrays for neural stimulation using organic semiconductors-cytotoxicity and pilot experiments in vivo.

Organic field effect transistors can be integrated into micromachined polyimide-based neural stimulation electrode arrays in order to build active switching matrices. With this approach, a matrix of N x M electrode contacts requires only N + M interconnects to a stimulator when active switching elements are used instead of N x M interconnects. In this paper, we demonstrated that pentacene-based organic field effect transistors (OFETs) can be used to drive stimulation currents through neural electrodes in a physiological-like environment. In order to prove the general applicability as an implant material, the cytotoxicity of pentacene was evaluated with respect to potential effects on cell viability. The results of these tests indicate that extracts from pentacene inhibit neither proliferation nor metabolism of the tested mouse fibroblasts. However, some effect on cell spreading was observed when cells were in direct contact to pentacene for 48 h. In pilot experiments it was demonstrated for the very first time that pentacene transistors can be used as switching elements, acting as voltage-controlled current sources, capable of driving currents suitable for electrical stimulation of a peripheral nerve via a tripolar cuff electrode.

Design of contact zone topography for implantable high-channel electrical connectors.

Detachable high-channel electrical connections pose a bottleneck on the path to active implants with higher numbers of electrode contacts and miniaturized geometries. Not only low-resistance, reproducible and reliable contacts have to be realized but also seals that ensure electrical insulation in the harsh body environment. Using planar contact arrangements one can resort to laser microprocessing leading to minimal size connectors. However, this poses the need to carefully design the topographies within the contact zone. In this study, we assess different methods to design the topography of planar contact pad arrays. Using topographical analysis and evaluation of electrical functionality, influential mechanisms were identified and two functional ones have been selected.

An implantable ENG detector with in-system velocity selective recording (VSR) capability.

Detection and classification of electroneurogram (ENG) signals in the peripheral nervous system can be achieved by velocity selective recording (VSR) using multi-electrode arrays. This paper describes an implantable VSR-based ENG recording system representing a significant development in the field since it is the first system of its type that can record naturally evoked ENG and be interfaced wirelessly using a low data rate transcutaneous link. The system consists of two CMOS ASICs one of which is placed close to the multi-electrode cuff array (MEC), whilst the other is mounted close to the wireless link. The digital ASIC provides the signal processing required to detect selectively ENG signals based on velocity. The design makes use of an original architecture that is suitable for implantation and reduces the required data rate for transmission to units placed outside the body. Complete measured electrical data from samples of the ASICs are presented that show that the system has the capability to record signals of amplitude as low as 0.5 µV, which is adequate for the recording of naturally evoked ENG. In addition, measurements of electrically evoked ENG from the explanted sciatic nerves of Xenopus Laevis frogs are presented.

Influence of Anatomical Detail and Tissue Conductivity Variations in Simulations of Multi-Contact Nerve Cuff Recordings.

Accurate simulations of peripheral nerve recordings are needed to develop improved neuroprostheses. Previous models of peripheral nerves contained simplifications whose effects have not been investigated. We created a novel detailed finite element (FE) model of a peripheral nerve, and used it to carry out a sensitivity analysis of several model parameters. To construct the model, in vivo recordings were obtained in a rat sciatic nerve using an 8-channel nerve cuff electrode, after which the nerve was imaged using magnetic resonance imaging (MRI). The FE model was constructed based on the MRI data, and included progressive branching of the fascicles. Neural pathways were defined in the model for the tibial, peroneal and sural fascicles. The locations of these pathways were selected so as to maximize the correlations between the simulated and in vivo recordings. The sensitivity analysis showed that varying the conductivities of neural tissues had little influence on the ability of the model to reproduce the recording patterns obtained experimentally. On the other hand, the increased anatomical detail did substantially alter the recording patterns observed, demonstrating that incorporating fascicular branching is an important consideration in models of nerve cuff recordings. The model used in this study constitutes an improved simulation tool and can be used in the design of neural interfaces.

Design, in vitro and in vivo assessment of a multi-channel sieve electrode with integrated multiplexer.

This paper reports on the design, in vitro and in vivo investigation of a flexible, lightweight, polyimide based implantable sieve electrode with a hybrid assembly of multiplexers and polymer encapsulation. The integration of multiplexers enables us to connect a large number of electrodes on the sieve using few input connections. The implant assembly of the sieve electrode with the electronic circuitry was verified by impedance measurement. The 27 platinum electrodes of the sieve were coated with platinum black to reduce the electrode impedance. The impedance magnitude of the electrode sites on the sieve (geometric surface area 2,200 microm(2)) was |Z(f=1kHz)| = 5.7 kOmega. The sieve electrodes, encased in silicone, have been implanted in the transected sciatic nerve of rats. Initial experiments showed that axons regenerated through the holes of the sieve and reinnervated distal target organs. Nerve signals were recorded in preliminary tests after 3-7 months post-implantation.

Very low-noise ENG amplifier system using CMOS technology.

In this paper, we describe the design and testing of a system for recording electroneurographic signals (ENG) from a multielectrode nerve cuff (MEC). This device, which is an extension of the conventional nerve signal recording cuff, enables ENG to be classified by action potential velocity. In addition to electrical measurements, we provide preliminary in vitro data obtained from frogs that demonstrate the validity of the technique for the first time. Since typical ENG signals are extremely small, on the order of 1 1 microV, very low-noise, high-gain amplifiers are required. The ten-channel system we describe was realized in a 0.8 microm CMOS technology and detailed measured results are presented. The overall gain is 10 000 and the total input-referred root mean square (rms) noise in a bandwidth 1 Hz-5 kHZ is 291 nV. The active area is 12 mm(2) and the power consumption is 24 mW from +/-2.5 V power supplies.

Development of a multichannel implantable connector.

Further development of active implantable medical devices (AIMDs) coming along with higher channel counts and improved maintainability raises the requirements for implantable connectors in such systems. We developed a concept for an implantable multichannel connector. Contact pads manufactured by laser-structuring that are embedded into a silicone substrate serve as contact partners. Processing features specific to two laser technologies were exploited not only to cut the materials but also to 3D-shape the surfaces of the contact pads. First tests for the long-term behavior show stable contact and isolation properties during 6 weeks of soaking at elevated temperature.

Non-hermetic encapsulation for implantable electronic devices based on epoxy.

Hermetic and non-hermetic implant packaging are the two strategies to protect electronic systems from the humid conditions inside the human body. Within the scope of this work twelve different material combinations for a non-hermetic, high-reliable epoxy based encapsulation technique were characterized. Three EPO-TEK (ET) epoxies and one low budget epoxy were chosen for studies with respect to their processability, water vapor transmission rate (WVTR) and adhesion to two different ceramic-based substrates as well as to one standard FR4-substrate. Setups were built to analyze the mentioned properties for at least 30 days using an aging test in a moist environment. As secondary test subjects, commercially available USB flash drives (UFD) were successfully encapsulated inside the epoxies, soaked in phosphate buffered saline (PBS, pH=7.4), stored in an incubator (37°C) and tested for 256 days without failure. By means of epoxy WVTR (0.0278 g/day/m(2)) and degrease of adhesion (24.59 %) during 30 days in PBS, the combination of the standard FR4-substrate and the epoxy ET 301-2 was found to feature the best encapsulation properties. If a ceramic-based electronic system has to be used, the most promising combination consists of the alumina substrate and the epoxy ET 302-3M (WVTR: 0.0588 g/day/m(2); adhesion drop: 49.58 %).

Noninvasive measurement of torque development in the rat foot: measurement setup and results from stimulation of the sciatic nerve with polyimide-based cuff electrodes.

In neural rehabilitation, selective activation of muscles after electrical stimulation is mandatory for control of paralyzed limbs. For an evaluation of electrode selectivity, a setup to noninvasively measure the force development after electrical stimulation in the rat foot was developed. The setup was designed in accordance to the anatomical features of the rat model to test the isometric torque development at given ankle positions in an intact leg. In this paper, the setup design and development is presented and discussed. In a first study, the selectivity of small nerve cuffs with 12 electrodes implanted around the rat sciatic nerve was investigated. Special attention was drawn to the performance of the torque measurement setup in comparison to electrophysiological data obtained from compound muscle action potential recordings. Using one cuff around the nerve, electrical stimulation on different electrode tripoles led to plantarflexion and dorsiflexion of the foot without an a priori alignment of the cuff.

Morphological and electrochemical properties of an explanted PtIr electrode array after 15 months in vivo.

We investigated the morphological and electrochemical properties of an explanted laser-machined 32 channel electrocorticogram (ECoG) electrode array made of platinum-iridium and silicone rubber. It was connected to a wireless brain-computer interface (BCI) and implanted in a sheep for more than 15 months. Recordings and stimulations of cortical activity were conducted over the whole period on a regularly basis. Currently, this is the longest in vivo study for this type of ECoG electrode array. Results were compared with an unused electrode array of same dimensions, material and production method. Visual inspections revealed no significant material alterations, despite organic residuals which could be easily removed though. Electrochemical impedance measurements also attested proper long-term stability of magnitude and phase, the difference between explanted electrode contacts and those of the unused array were found negligible.

A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems.

A polymer-metal two step sealing concept for hermetic neural implant packages.

In this paper, we introduce a technique for double-sealed ceramic packages for the long-term protection of implanted electronics against body fluids. A sequential sealing procedure consisting of a first step, during which the package is sealed with epoxy, protecting the implant electronics from aggressive flux fumes. These result from the application of the actual moisture barrier which is a metal seal applied in a second step by soft soldering. Epoxy sealing is carried out in helium atmosphere for later fine leak testing. The solder seal is applied on the laboratory bench. After the first sealing step, a satisfactory barrier for moisture is already achieved with values for helium leakage of usually LHe = 6·10(-8) mbar 1 s(-1). After solder sealing, a very low leakage rate of LHe ≤ 1·10(-12) mbar 1 s(-1) was found, which was the lower detection limit of the measurement setup, suggesting excellent hermeticity and hence moisture barrier. Presuming an implant package volume of V ≥ 0.5 cm(3), the time to reach a critical humidity of p = 5000 ppm H2O inside the package will be longer than any anticipated average life of human patients.

Cuff electrodes for very small diameter nerves -- prototyping and first recordings in vivo.

A fabrication method for cuff electrodes to interface small nerves was developed. Medical grade silicone rubber conforms the body of the cuff and insulation of the wires, platinum was used as metal for the embedded wiring and contacts. Planar electrode arrays where fabricated using a picosecond laser and then positioned into a carrying tube to provide the third dimension with the desired inner diameter (Ø 0.3-0.5 mm). The post preparation of the cuffs after structuring allows the fabrication of a stable self-closing flap that insulates the opening slit of the cuff without the need of extra sutures. Basic for the success of the cuff is the laser-based local thinning of both the silicone rubber and the metal at defined sections. This is critical to permit the PDMS' body to dominate the mechanical properties. Finite element modeling was applied to optimize the displacement ability of the cuff, leading to design capable of withstanding multiple implantation procedures without wire damage. Furthermore, the contact's surface was roughened by laser patterning to increase the charge injection capacity of Pt to 285 µC/cm(2) measured by voltage transient detection during pulse testing. The cuff electrodes were placed on a small sympathetic nerve of an adult female Sprague-Dawley rat for recording of spontaneous and evoked neural activity in vivo.