Klaus Peter Koch

Assessment of Biocompatibility of Chronically Implanted Polyimide and Platinum Intrafascicular Electrodes

Longitudinal intrafascicular electrodes (LIFEs) are electrodes designed to be placed inside the peripheral nerve to improve stimulation selectivity and to increase the recording signal-to-noise ratio. We evaluated the functional and morphological effects of either Pt wire LIFEs or polyimide-based thin-film LIFEs implanted in the rat sciatic nerve for 3 mo. The newly designed thin-film LIFEs are more flexible, can be micromachined and allow placement of more active electrode sites than conventional Pt LIFEs. Functional results at 1 mo indicated an initial decline in the nerve conduction velocity and in the amplitude of muscle responses, which recovered during the following 2 mo towards normal values. Morphological results showed that both types of LIFEs induced a mild scar response and a focal but chronic inflammatory reaction, which were limited to a small area around the electrode placed in the nerve. Both types of LIFEs can be considered biocompatible and cause reversible, minimal nerve damage

Implantable biomedical microsystems for neural prostheses

In the following article, the technologies to fabricate polyimide-based thin and flexible substrates with monolithically integrated electrode arrays and printed circuit boards (PCB) for hybrid electronic assemblies as well as an assembling technique that connects bare electronic dice with flexible PCBs are presented. The concept of modular, flexible biomedical microsystems as neural prostheses is introduced in general and described in detail in three examples. A cuff electrode with integrated multiplexer circuitry and standard implantable cables represents the combination of microtechnology with precision mechanics; a sieve electrode used as an implant in peripheral nerve regeneration studies demonstrates the next level of integration density but still uses a cable connection; and last, joint effort to fabricate the demonstrator of a vision prosthesis that is completely implantable in the eye with a wireless link for energy supply and data transmission is presented. System design, hybrid assembling technology, and flexible multilayer encapsulation using parylene and silicone rubber are the key components for creating a new generation of neural prostheses for complex and challenging new applications.

An implantable neuroprosthesis for standing and walking in paraplegia: 5-year patient follow-up

We present the results of a 5-year patient follow-up after implantation of an original neuroprosthesis. The system is able to stimulate both epimysial and neural electrodes in such a way that the complete flexor-extensor chain of the lower limb can be activated without using the withdrawal reflex. We demonstrate that standing and assisted walking are possible, and the results have remained stable for 5 years. Nevertheless, some problems were noted, particularly regarding the muscle response on the epimysial channels. Analysis of the electrical behaviour and thresholds indicated that the surgical phase is crucial because of the sensitivity of the functional responses to electrode placement. Neural stimulation proved to be more efficient and more stable over time. This mode requires less energy and provides more selective stimulation. This FES system can be improved to enable balanced standing and less fatiguing gait, but this will require feedback on event detection to trigger transitions between stimulation sequences, as well as feedback to the patient about the state of his lower limbs.

On the use of wavelet denoising and spike sorting techniques to process electroneurographic signals recorded using intraneural electrodes.

Among the possible interfaces with the peripheral nervous system (PNS), intraneural electrodes represent an interesting solution for their potential advantages such as the possibility of extracting spikes from electroneurographic (ENG) signals. Their use could increase the precision and the amount of information which can be detected with respect to other processing methods. In this study, in order to verify this assumption, thin-film longitudinal intrafascicular electrodes (tfLIFE) were implanted in the sciatic nerve of rabbits. Various sensory stimuli were applied to the hind limb of the animal and the elicited ENG signals were recorded using the tfLIFEs. These signals were processed to determine whether the different types of information can be decoded. Signals were wavelet denoised and spike sorted. Support vector machines were trained to use the spike waveforms found to infer the stimulus applied to the rabbit. This approach was also compared with previously used ENG-processing methods. The results indicate that the combination of wavelet denoising and spike sorting techniques can increase the amount of information extractable from ENG signals recorded with intraneural electrodes. This strategy could allow the development of more effective closed-loop neuroprostheses and hybrid bionic systems connecting the human nervous system with artificial devices.

Real-time monitoring of the recurrent laryngeal nerve: An observational clinical trial

BACKGROUND A variety of tools has been developed to identify nerve structures and to lower the risk of nerval injury during thyroid surgery. These tools are usually based on intermittent electrophysiological tracing of the nerves, but its use is still associated with permanent recurrent laryngeal nerve (RLN) injury. We are now presenting the results of the implementation of a novel real-time nerve monitoring system, based on a new vagal nerve cuff electrode. METHODS Nineteen consecutive patients scheduled for thyroid surgery (17 with benign, 2 with malignant disease), were enrolled in this observational trial. The flexible cuff electrode was implanted during each operation and atraumatically surrounded the vagal nerve. The evoked potentials were sensed by standard thyroid electrodes. Electrical stimulation and recording were achieved through a multichannel electromyography (EMG) system. The signal analysis was performed in real-time by specially designed software. RESULTS The cuff electrode did not cause any complications during or after the surgery. In all patients, stable and reproducible signals were easily evoked. The mean time required to place the electrode was 6.5 min. The mean overall vagal nerve stimulation time was 65 min. No permanent RLN lesions were detected in any patient. One patient with a postoperative bleeding from a strap muscle vein required a wound revision, which was performed without nerve monitoring. This patient experienced a temporary partial impairment of the left vocal cord. No hypoparathyroidism was observed in any patient postoperatively. CONCLUSIONS The presented technique of real-time continuous RLN monitoring by stimulation of the vagal nerve is feasible, safe, reproducible, and easy to perform. In addition, this new system is compatible with existing equipment and can be used as an add-on with conventional nerve monitoring devices during thyroid surgery.

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.

A new system for continuous recurrent laryngeal nerve monitoring

Existing nerve monitoring devices in thyroid surgery are ‐ except for one ‐ mainly intermittently working nerve identification tools. We present a new vagal electrode which allows true continuous monitoring of the recurrent laryngeal nerve (RLN). The electrode was designed as a tripolar hybrid cuff electrode consisting of polyimide, gold and platinum layers embedded in a flexible silicon cuff which can be opened at the long side for introducing the nerve. It is fully implantable and atraumatic. The evoked potentials are sensed by standard thyroid electrodes. Real‐time signal analysis and audio feedback are achieved by specially designed software. Homogeneous and stable signals were recorded throughout the operations. Thus real‐time computer‐based signal analysis was possible. Evoked potentials reached 300–900 mV. Mean time to place the cuff electrode was 5.5 min. The nerve was stimulated a mean of 63 min (range 55–99 min). No RLN lesions were detected postoperatively. The new vagal electrode was easy to handle and led to stable and reproducible signals. The stimulation current could be kept extremely low due to the special geometry of the electrode. It offers the possibility for uninterrupted, continuous laryngeal nerve monitoring in thyroid surgery. In an ongoing clinical trial its compatibility as an add‐on for existing nerve monitoring devices is being tested.

High Resolution Electroencephalography in Freely Moving Mice

Electroencephalography (EEG) is a standard tool for monitoring brain states in humans. Understanding the molecular and cellular mechanisms underlying diverse EEG rhythms can be facilitated by using mouse models under molecular, pharmacological, or electrophysiological manipulations. The small size of the mouse brain, however, poses a severe limitation in the spatial information of EEG. To overcome this limitation, we devised a polyimide based microelectrode array (PBM array) with nanofabrication technologies. The microelectrode contains 32 electrodes, weighs 150 mg, and yields noise-insensitive signals when applied on the mouse skull. The high-density microelectrode allowed both global and focused mapping of high resolution EEG (HR-EEG) in the mouse brain. Mapping and dynamical analysis tools also have been developed to visualize the dynamical changes of spatially resolved mouse EEG. We demonstrated the validity and utility of mouse EEG in localization of the seizure onset in absence seizure model and phase dynamics of abnormal theta rhythm in transgenic mice. Dynamic tracking of the EEG map in genetically modified mice under freely moving conditions should allow study of the molecular and cellular mechanisms underlying the generation and dynamics of diverse EEG rhythms.

New technologies in manufacturing of different implantable microelectrodes as an interface to the peripheral nervous system

Implantable microelectrodes represent the direct interface between biological tissue and technical systems. Different designs like cuff, shaft, sieve, and needle electrodes were developed. The results of the different electrodes were compared and discussed. Microfabrication methods enable the design of novel kinds of electrodes including active electronics. Integrated electronic circuitry can reduce the number of connection lines to the electrode and increase the signal quality. This paper presents some examples of production technology and designs of neural prostheses for recording and stimulation

Total Mesorectal Excision with Intraoperative Assessment of Internal Anal Sphincter Innervation Provides New Insights into Neurogenic Incontinence

BACKGROUND The aim of this prospective study was to assess internal anal sphincter (IAS) innervation in patients undergoing total mesorectal excision (TME) by intraoperative neuromonitoring (IONM). STUDY DESIGN Fourteen patients underwent TME. IONM was carried out through pelvic splanchnic nerve stimulation under continuous electromyography of the IAS. Anorectal function was assessed with the digital rectal examination scoring system and a standardized questionnaire. RESULTS Nine of 11 patients who underwent low anterior resection had positive IONM results, with stimulation-induced increased IAS electromyographic amplitudes (median 0.23 μV (interquartile range [IQR] 0.05, 0.56) vs median 0.89 μV (IQR 0.64, 1.88), p < 0.001) after TME. The patients with the positive IONM results were continent after stoma closure. Of 2 patients with negative IONM results, 1 had fecal incontinence after closure of the defunctioning stoma and received a permanent sigmoidostomy. In the other patient the defunctioning stoma was deemed permanent due to decreased anal sphincter function. In 3 patients who underwent abdominoperineal excision, IONM assessed denervation of the IAS after performance of the abdominal part. CONCLUSIONS This study demonstrated that IONM of IAS innervation in rectal cancer patients is feasible and may predict neurogenic fecal incontinence.