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.

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.

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.

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.

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 %).

Mapping of sheep sensory cortex with a novel microelectrocorticography grid.

Microelectrocorticography (µECoG) provides insights into the cortical organization with high temporal and spatial resolution desirable for better understanding of neural information processing. Here we evaluated the use of µECoG for detailed cortical recording of somatosensory evoked potentials (SEPs) in an ovine model. The approach to the cortex was planned using an MRI-based 3D model of the sheep's brain. We describe a minimally extended surgical procedure allowing placement of two different µECoG grids on the somatosensory cortex. With this small craniotomy, the frontal sinus was kept intact, thus keeping the surgical site sterile and making this approach suitable for chronic implantations. We evaluated the procedure for chronic implantation of an encapsulated µECoG recording system. During acute and chronic recordings, significant SEP responses in the triangle between the ansate, diagonal, and coronal sulcus were identified in all animals. Stimulation of the nose, upper lip, lower lip, and chin caused a somatotopic lateral-to-medial, ipsilateral response pattern. With repetitive recordings of SEPs, this somatotopic pattern was reliably recorded for up to 16 weeks. The findings of this study confirm the previously postulated ipsilateral, somatotopic organization of the sheep's sensory cortex. High gamma band activity was spatially most specific in the comparison of different frequency components of the somatosensory evoked response. This study provides a basis for further acute and chronic investigations of the sheep's sensory cortex by characterizing its exact position, its functional properties, and the surgical approach with respect to macroanatomical landmarks.

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.

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.

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 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.

Fibre-selective recording from the peripheral nerves of frogs using a multi-electrode cuff.

OBJECTIVE: We investigate the ability of the method of velocity selective recording (VSR) to determine the fibre types that contribute to a compound action potential (CAP) propagating along a peripheral nerve. Real-time identification of the active fibre types by determining the direction of action potential propagation (afferent or efferent) and velocity might allow future neural prostheses to make better use of biological sensor signals and provide a new and simple tool for use in fundamental neuroscience. APPROACH: Fibre activity was recorded from explanted Xenopus Laevis frog sciatic nerve using a single multi-electrode cuff that records whole nerve activity with 11 equidistant ring-shaped electrodes. The recorded signals were amplified, delayed against each other with variable delay times, added and band-pass filtered. Finally, the resulting amplitudes were measured. MAIN RESULT: Our experiments showed that electrically evoked frog CAP was dominated by two fibre populations, propagating at around 20 and 40 m/s, respectively. The velocity selectivity, i.e. the ability of the system to discriminate between individual populations was increased by applying band-pass filtering. The method extracted an entire velocity spectrum from a 10 ms CAP recording sample in real time. SIGNIFICANCE: Unlike the techniques introduced in the 1970s and subsequently, VSR requires only a single nerve cuff and does not require averaging to provide velocity spectral information. This makes it potentially suitable for the generation of highly-selective real-time control-signals for future neural prostheses. In our study, electrically evoked CAPs were analysed and it remains to be proven whether the method can reliably classify physiological nerve traffic.

The theory of velocity selective neural recording: a study based on simulation.

This paper describes the improvements to the theory of velocity selective recording and some simulation results. In this method, activity in different groups of axons is discriminated by their propagation velocity. A multi-electrode cuff and an array of amplifiers produce multiple neural signals; if artificial delays are inserted and the signals are added, the activity in axons of the matched velocity are emphasized. We call this intrinsic velocity selective recording. However, simulation shows that interpreting the time signals is then not straight-forward and the selectivity Q(v) is low. New theory shows that bandpass filters improve the selectivity and explains why this is true in the time domain. A simulation study investigates the limits on the available velocity selectivity both with and without additive noise and with reasonable sampling rates and analogue-to-digital conversion parameters. Bandpass filters can improve the selectivity by factors up to 7 but this depends on the speed of the action potential and the signal-to-noise ratio.

Hermetic glass soldered micro-packages for a vision prosthesis.

Micro-packages based on alumina ceramics hermetically sealed with glass solder were fabricated and tested over a 1.5 years period under accelerated aging at 85 °C. A device for sealing the 1.2 mm high, and ø10mm packages while cooling the critical centre of the package containing the electronics was developed. Heating of the rim up to 550 °C while maintaining the package centre below 300°C was successful, allowing a symmetrical heating of the device during the sealing procedure. The fabricated packages with an inner volume of 0.05 cc were backfilled with helium and tested for hermeticity with a fine leak tester. Samples passing the fine leak (1•10(-12) atm•cc/s) test were attached to a larger chamber containing a humidity sensor. Some devices covered in PDMS and some directly exposed were stored at 85 °C in water to measure the humidity intrusion into the device due to deterioration of glass solder. 1 out of the 8 successfully fabricated devices failed after 5 years extrapolated lifetime. Two of the devices have kept constant humidity levels while others gradually rise. Nevertheless, 7 out of 8 have maintained a level below 17,000 ppm humidity. Furthermore, the deterioration of glass solder was electrically and optically studied over a year's period showing no corrosion of glass if properly coated in PDMS.

A 232-channel retinal vision prosthesis with a miniaturized hermetic package.

Miniaturization of implantable devices while drastically increasing the number of stimulation channels is one of the greatest challenges in implant manufacturing because a small but hermetic package is needed that provides reliable protection for the electronics over decades. Retinal vision prostheses are the best example for it. This paper presents a miniaturized 232-channel vision prosthesis, summarizing the studies on the individual technologies that were developed, improved and combined to fabricate a telemetrically powered retinal device sample. The implantable unit, which is made out of a high temperature co-fired alumina ceramic package containing hermetic feedthroughs, electronic circuitry and a radio frequency coil for powering is manufactured through a modified screen-printing/lasering process. The package is sealed with solder glass to provide unaffected inductive coupling to the telemetric transmitter. A 0.05 cc inner volume allows helium leak testing and mathematical lifetime estimations for moisture-induced failure of up to 100 years. The feedthroughs contact a thin-film polyimide electrode array that utilizes DLC and SiC coatings for improved interlayer adhesion of the metallic tracks to the polymer carrier. Two metal layers allow integrated wiring of the electrode array within the very limited space.

Hermetic electronic packaging of an implantable brain-machine-interface with transcutaneous optical data communication.

Future brain-computer-interfaces (BCIs) for severely impaired patients are implanted to electrically contact the brain tissue. Avoiding percutaneous cables requires amplifier and telemetry electronics to be implanted too. We developed a hermetic package that protects the electronic circuitry of a BCI from body moisture while permitting infrared communication through the package wall made from alumina ceramic. The ceramic package is casted in medical grade silicone adhesive, for which we identified MED2-4013 as a promising candidate.