In a porcine model of implantable pacemakers for pediatric unilateral diaphragm paralysis, the phrenic nerve is the best target.

BACKGROUND: A frequent complication of Fontan operations is unilateral diaphragmatic paresis, which leads to hemodynamic deterioration of the Fontan circulation. A potential new therapeutic option is the unilateral diaphragmatic pacemaker. In this study, we investigated the most effective stimulation location for a potential fully implantable system in a porcine model. METHODS: Five pigs (20.8 ± 0.95 kg) underwent implantation of a customized cuff electrode placed around the right phrenic nerve. A bipolar myocardial pacing electrode was sutured adjacent to the motor point and peripherally at the costophrenic angle (peripheral diaphragmatic muscle). The electrodes were stimulated 30 times per minute with a pulse duration of 200 µs and a stimulation time of 300 ms. Current intensity was the only variable changed during the experiment. RESULTS: Effective stimulation occurred at 0.26 ± 0.024 mA at the phrenic nerve and 7 ± 1.22 mA at the motor point, a significant difference in amperage (p = 0.005). Even with a maximum stimulation of 10 mA at the peripheral diaphragm muscle, however, no effective stimulation was observed. CONCLUSION: The phrenic nerve seems to be the best location for direct stimulation by a unilateral thoracic diaphragm pacemaker in terms of the required amperage level in a porcine model.

A porcine model of postoperative hemi-diaphragmatic paresis to evaluate a unilateral diaphragmatic pacemaker.

Unilateral phrenic nerve damage is a dreaded complication in congenital heart surgery. It has deleterious effects in neonates and children with uni-ventricular circulation. Diaphragmatic palsy, caused by phrenic nerve damage, impairs respiratory function, especially in new-borns, because their respiration depends on diaphragmatic contractions. Furthermore, Fontan patients with passive pulmonary perfusion are seriously affected by phrenic nerve injury, because diaphragmatic contraction augments pulmonary blood flow. Diaphragmatic plication is currently employed to ameliorate the negative effects of diaphragmatic palsy on pulmonary perfusion and respiratory mechanics. This procedure attenuates pulmonary compression by the abdominal contents. However, there is no contraction of the plicated diaphragm and consequently no contribution to the pulmonary blood flow. Hence, we developed a porcine model of unilateral diaphragmatic palsy in order to evaluate a diaphragmatic pacemaker. Our illustrated step-by-step description of the model generation enables others to replicate and use our model for future studies. Thereby, it might contribute to investigation and advancement of potential improvements for these patients.

Proof of concept of an accelerometer as a trigger for unilateral diaphragmatic pacing: a porcine model.

BACKGROUND: Unilateral diaphragmatic paralysis in patients with univentricular heart is a known complication after pediatric cardiac surgery. Because diaphragmatic excursion has a significant influence on perfusion of the pulmonary arteries and hemodynamics in these patients, unilateral loss of function leads to multiple complications. The current treatment of choice, diaphragmatic plication, does not lead to a full return of function. A unilateral diaphragmatic pacemaker has shown potential as a new treatment option. In this study, we investigated an accelerometer as a trigger for a unilateral diaphragm pacemaker (closed-loop system). METHODS: Seven pigs (mean weight 20.7 ± 2.25 kg) each were implanted with a customized accelerometer on the right diaphragmatic dome. Accelerometer recordings (mV) of the diaphragmatic excursion of the right diaphragm were compared with findings using established methods (fluoroscopy [mm]; ultrasound, M-mode [cm]). For detection of the amplitude of diaphragmatic excursions, the diaphragm was stimulated with increasing amperage by a cuff electrode implanted around the right phrenic nerve. RESULTS: Results with the different techniques for measuring diaphragmatic excursions showed correlations between accelerometer and fluoroscopy values (correlation coefficient 0.800, P < 0.001), accelerometer and ultrasound values (0.883, P < 0.001), and fluoroscopy and ultrasound values (0.816, P < 0.001). CONCLUSION: The accelerometer is a valid method for detecting diaphragmatic excursion and can be used as a trigger for a unilateral diaphragmatic pacemaker.

Laparoscopic Electromyography and Electrostimulation of the Gastrointestinal Tract Before Placement of Theranostic Devices.

NEED: Electrical stimulation (ES) is a promising therapy for multisegmental gastrointestinal (GI) motility disorders such as gastroparesis with slow-transit constipation or chronic intestinal pseudo-obstruction. Wireless communicating GI devices for smart sensing and ES-based motility modulation will soon be available. Before placement, a potential benefit for each GI segment must be intraoperatively assessed. TECHNICAL SOLUTION: A minimally invasive multisegmental electromyography (EMG) analysis with ES of the GI tract is required. PROOF OF CONCEPT: Two porcine experiments were performed with a laparoscopic setup. Multiple hook-needle electrodes were subserosally applied in the stomach, duodenum, jejunum, ileum, and colon. EMG signals were acquired for computer-assisted motility analysis. Gastric ES, duodenal ES, jejunal ES, ileal ES, and colonic ES were applied. NEXT STEPS: Further technological and rapid regulatory solutions are desired to initialize a clinical trial of the next generation devices in the near future. CONCLUSION: We demonstrate a laparoscopic strategy with EMG analysis and ES of multiple GI segments. Thus, GI function may be evaluated before theranostic devices are placed. Extended GI resection or organ transplantation may be delayed or even avoided in affected patients.

A multi-Kalman filter-based approach for decoding arm kinematics from EMG recordings.

BACKGROUND: Remarkable work has been recently introduced to enhance the usage of Electromyography (EMG) signals in operating prosthetic arms. Despite the rapid advancements in this field, providing a reliable, naturalistic myoelectric prosthesis remains a significant challenge. Other challenges include the limited number of allowed movements, lack of simultaneous, continuous control and the high computational power that could be needed for accurate decoding. In this study, we propose an EMG-based multi-Kalman filter approach to decode arm kinematics; specifically, the elbow angle (θ), wrist joint horizontal (X) and vertical (Y) positions in a continuous and simultaneous manner. RESULTS: Ten subjects were examined from which we recorded arm kinematics and EMG signals of the biceps, triceps, lateral and anterior deltoid muscles corresponding to a randomized set of movements. The performance of the proposed decoder is assessed using the correlation coefficient (CC) and the normalized root-mean-square error (NRMSE) computed between the actual and the decoded kinematic. Results demonstrate that when training and testing the decoder using same-subject data, an average CC of 0.68 ± 0.1, 0.67 ± 0.12 and 0.64 ± 0.11, and average NRMSE of 0.21 ± 0.06, 0.18 ± 0.03 and 0.24 ± 0.07 were achieved for θ, X, and Y, respectively. When training the decoder using the data of one subject and decoding the data of other subjects, an average CC of 0.61 ± 0.19, 0.61 ± 0.16 and 0.48 ± 0.17, and an average NRMSE of 0.23 ± 0.07, 0.2 ± 0.05 and 0.38 ± 0.15 were achieved for θ, X, and Y, respectively. CONCLUSIONS: These results suggest the efficacy of the proposed approach and indicates the possibility of obtaining a subject-independent decoder.

Five-fold Gastrointestinal Electrical Stimulation With Electromyography-based Activity Analysis: Towards Multilocular Theranostic Intestinal Implants.

BACKGROUND/AIMS: Motility disorders are common and may affect the entire gastrointestinal (GI) tract but current treatment is limited. Multilocular sensing of GI electrical activity and variable electrical stimulation (ES) is a promising option. The aim of our study is to investigate the effects of adjustable ES on poststimulatory spike activities in 5 GI segments. METHODS: Six acute porcine experiments were performed with direct ES by 4 ES parameter sets (30 seconds, 25 mA, 500 microseconds or 1000 microseconds, 30 Hz or 130 Hz) applied through subserosal electrodes in the stomach, duodenum, ileum, jejunum, and colon. Multi-channel electromyography of baseline and post-stimulatory GI electrical activity were recorded for 3 minutes with hook needle and hook-wire electrodes. Spike activities were algorithmically calculated, visualized in a heat map, and tested for significance by Poisson analysis. RESULTS: Post-stimulatory spike activities were markedly increased in the stomach (7 of 24 test results), duodenum (8 of 24), jejunum (23 of 24), ileum (18 of 24), and colon (5 of 24). ES parameter analysis revealed that 80.0% of the GI parts (all but duodenum) required a pulse width of 1000 microseconds, and 60.0% (all but jejunum and colon) required 130 Hz frequency for maximum spike activity. Five reaction patterns were distinguished, with 30.0% earlier responses (type I), 42.5% later or mixed type responses (type II, III, and X), and 27.5% non-significant responses (type 0). CONCLUSIONS: Multilocular ES with variable ES parameters is feasible and may significantly modulate GI electrical activity. Automated electromyography analysis revealed complex reaction patterns in the 5 examined GI segments.

Technical, Medical and Ethical Challenges in Networks of Smart Active Implants.

Networks of distributed interactive micro-implants could enhance the treatment of otoneurological conditions such as tinnitus or restore impaired complex physiological/ motor functions such as gastrointestinal motility or grasping. For this, an electrical stimulation of neural and muscular tissue is a key prerequisite. Challenges in the development of such interactive micro-implants are the complex human-machine interface, the wireless power supply, and the long-term stability of implants as well as secure and safe signal transmission. This paper addresses all these topics as well as the ethical, legal and social implications of smart implant networks in general. First achievements of the German innovation cluster INTAKT will be presented.

Prolonged Corrosion Stability of a Microchip Sensor Implant during In Vivo Exposure.

A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS) prepared using 0.25 µm complementary metal-oxide-semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.

Extracorporeal Stimulation of Sacral Nerve Roots for Observation of Pelvic Autonomic Nerve Integrity: Description of a Novel Methodological Setup.

INTRODUCTION: Neurophysiologic monitoring can improve autonomic nerve sparing during critical phases of rectal cancer surgery. OBJECTIVES: To develop a system for extracorporeal stimulation of sacral nerve roots. METHODS: Dedicated software controlled a ten-electrode stimulation array by switching between different electrode configurations and current levels. A built-in impedance and current level measurement assessed the effectiveness of current injection. Intra-anal surface electromyography (sEMG) informed on targeting the sacral nerve roots. All tests were performed on five pig specimens. RESULTS: During switching between electrode configurations, the system delivered 100% of the set current (25 mA, 30 Hz, 200 µs cathodic pulses) in 93% of 250 stimulation trains across all specimens. The impedance measured between single stimulation array contacts and corresponding anodes across all electrode configurations and specimens equaled 3.7 ± 2.5 kΩ. The intra-anal sEMG recorded a signal amplitude increase as previously observed in the literature. When the stimulation amplitude was tested in the range from 1 to 21 mA using the interconnected contacts of the stimulation array and the intra-anal anode, the impedance remained below 250 Ω and the system delivered 100% of the set current in all cases. Intra-anal sEMG showed an amplitude increase for current levels exceeding 6 mA. CONCLUSION: The system delivered stable electric current, which was proved by built-in impedance and current level measurements. Intra-anal sEMG confirmed the ability to target the branches of the autonomous nervous system originating from the sacral nerve roots. SIGNIFICANCE: Stimulation outside of the operative field during rectal cancer surgery is feasible and may improve the practicality of pelvic intraoperative neuromonitoring.

Long-term decoding of movement force and direction with a wireless myoelectric implant.

OBJECTIVE: The ease of use and number of degrees of freedom of current myoelectric hand prostheses is limited by the information content and reliability of the surface electromyography (sEMG) signals used to control them. For example, cross-talk limits the capacity to pick up signals from small or deep muscles, such as the forearm muscles for distal arm amputations, or sites of targeted muscle reinnervation (TMR) for proximal amputations. Here we test if signals recorded from the fully implanted, induction-powered wireless Myoplant system allow long-term decoding of continuous as well as discrete movement parameters with better reliability than equivalent sEMG recordings. The Myoplant system uses a centralized implant to transmit broadband EMG activity from four distributed bipolar epimysial electrodes. APPROACH: Two Rhesus macaques received implants in their backs, while electrodes were placed in their upper arm. One of the monkeys was trained to do a cursor task via a haptic robot, allowing us to control the forces exerted by the animal during arm movements. The second animal was trained to perform a center-out reaching task on a touchscreen. We compared the implanted system with concurrent sEMG recordings by evaluating our ability to decode time-varying force in one animal and discrete reach directions in the other from multiple features extracted from the raw EMG signals. MAIN RESULTS: In both cases, data from the implant allowed a decoder trained with data from a single day to maintain an accurate decoding performance during the following months, which was not the case for concurrent surface EMG recordings conducted simultaneously over the same muscles. SIGNIFICANCE: These results show that a fully implantable, centralized wireless EMG system is particularly suited for long-term stable decoding of dynamic movements in demanding applications such as advanced forelimb prosthetics in a wide range of configurations (distal amputations, TMR).

SEP-induced activity and its thermographic cortical representation in a murine model.

This article is a methodical report on the generation of reproducible changes in brain activity in a murine model. Somatosensory evoked potentials (SEP) are used to generate synchronized cortical activity. After electrical stimulation of mice forelimbs, the potentials were recorded with a flexible thin-film polyimide electrode structure directly from the cortex. Every registration included a simultaneous recording from both hemispheres that repeated four times to reproduce and compare the results. The SEPs in the murine model were shown to generate a very stable signal. The latency of the second positive wave (P2 wave) ranged between 16 and 19 ms, and the N1-P2 amplitude ranged between 39 and 48 µV. In addition, the temperature distribution of the cortex was acquired using infrared thermography. Surface cortical temperature changed during electrical stimulation without a clear hemispheric correlation. These initial results could be a step toward a better understanding of the different synchronized cortical activities and basic methods of evaluation of various mathematical algorithms to detect them.

Acquisition of myoelectric signals to control a hand prosthesis with implantable epimysial electrodes.

The acquisition of myoelectric signals from the Musculus deltoideus of a rhesus monkey is described. Such signals are aimed to be used as control signal for an active myoelectric hand prosthesis. For recording, implantable flexible, polyimide-based multi-site microelectrodes were placed epimysially on the muscle. EMG signals were recorded during voluntary goal-directed movements of the arm, and analyzed with respect to signal amplitude and frequency.

Electrode structures for acquisition and neural stimulation controlling the cardiovascular system.

In this study we present an innovative electrode system, for many different applications in the field of cardiovascular diseases. It is a combination of intelligent communicating dry-surface electrodes, which are able to interact with different sensors especially with an invasive, ultra flexible electrode-system. Dry and smart surface electrodes, which can be integrated in textiles and therefore such electrode are almost "invisible" for patients, are used for ECG acquisition and can be integrated in a communication network. In combination with a pulse oximeter or impedance spectroscopy the pulse transit time (PTT) can be calculated. Additionally, with invasive electrodes the nervous vagus can be stimulated and therefore cardiovascular functions can be controlled. The association of an implanted stimulator with an interacting and smart monitoring system results into a cardiovascular controlling. In this work we will focus on the feasibility, suitability, fabrication and characterization of invasive and dry-surface electrode systems as a basic element and foundation for cardiovascular regulation in a closed loop.

Flexible dry surface-electrodes for ECG long-term monitoring.

In this paper a new generation of dry electrodes for ECG-recording purposes is presented. These electrodes are flexible, biocompatible, biostable and perform a dry signal acquisition without the use of any electrolyte gel or adhesive. Thereby no skin preparation is needed. The material properties allow integration into textiles to form intelligent clothes for long-term monitoring duties. The electrodes can be washed together with the carrier textiles and provide a very good wearing comfort resulting in wide acceptance by the patients. The Department Medical Engineering and Neuroprosthetics of the Fraunhofer Institute for Biomedical Engineering developed these electrodes mainly to process the Electrocardiogram, however, in first tests they proved their capability even for other biosignal requirements like surface-EMG. In either case the signal quality of the dry electrodes is comparable to commercial Ag/AgCl gel-electrodes.

Long-term characterization of electrode materials for surface electrodes in biopotential recording.

The long-term electrical behavior of 16 different electrode materials was investigated by using continuous impedance spectroscopy over a period of 10 days. The materials included bare and electrolytically treated metals, metals coated with intrinsically conductive polymers, and polymers with conductive particles. Electrolytic treatment of metal electrodes yielded a significant impedance reduction. The lowest impedance values could be reached with the polymer-coated metal electrodes. The impedance behavior is an important aspect when choosing an electrode material, and has to be considered in signal processing. The choice of a material depends on the application of the electrode. Moreover, for long-term applications, the electrochemical stability of a material has to be considered.