The Duration and Intensity of High Frequency Alternating Current Influences the Degree and Recovery of Nerve Conduction Block.

OBJECTIVE: The purpose of this paper is to investigate the persistence of nerve blockade beyond the duration of applying high frequency alternating current (HFAC) to thinly myelinated and non-myelinated fibers, also termed a "carry-over effect". METHODS: In this study, we used electrically-evoked compound action potentials from isolated rat vagus nerves to assess the influence of 5 kHz HFAC amplitude and duration on the degree of the carry-over effect. Current amplitudes from 1-10 mA and 5 kHz durations from 10-120 seconds were tested. RESULTS: By testing 20 different combinations of 5 kHz amplitude and duration, we found a significant interaction between 5 kHz amplitude and duration on influencing the carry-over effect. CONCLUSION: The degree of carry-over effect was dependent on 5 kHz amplitude, as well as duration. SIGNIFICANCE: Utilizing the carry-over effect may be useful in designing energy efficient nerve blocking algorithms for the treatment of diseases influenced by nerve activity.

Recording and analysis of slow waves of the small intestine of mice with heart failure.

BACKGROUND: Gastrointestinal (GI) symptoms in heart failure (HF) patients are associated with increased morbidity and mortality. We hypothesized that HF reduces bioelectrical activity underlying peristalsis. In this study, we aimed to establish a method to capture and analyze slow waves (SW) in the small intestine in mice with HF. METHODS: We established a model of HF secondary to coronary artery disease in mice overexpressing tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells. The myoelectric activity was recorded from the small intestine in live animals under anesthesia. The low- and high-frequency components of SW were isolated in MATLAB and compared between the control (n = 12) and eTNAP groups (n = 8). C-kit-positive interstitial cells of Cajal (ICC) and Pgp9.5-positive myenteric neurons were detected by immunofluorescence. Myenteric ganglia were assessed by hematoxylin and eosin (H&E) staining. RESULTS: SW activity was successfully captured in vivo, with both high- and low-frequency components. Low-frequency component of SW was not different between endothelial TNAP (eTNAP) and control mice (mean[95% CI]: 0.032[0.025-0.039] vs. 0.040[0.028-0.052]). High-frequency component of SW showed a reduction eTNAP mice relative to controls (0.221[0.140-0.302] vs. 0.394[0.295-0.489], p < 0.01). Dysrhythmia was also apparent upon visual review of signals. The density of ICC and neuronal networks remained the same between the two groups. No significant reduction in the size of myenteric ganglia of eTNAP mice was observed. CONCLUSIONS: A method to acquire SW activity from small intestines in vivo and isolate low- and high-frequency components was established. The results indicate that HF might be associated with reduced high-frequency SW activity.

Electrophysiological modeling of the effect of potassium channel blockers on the distribution of stimulation wave in the human gastric wall cells.

The purpose of this study is to model the electrophysiological behavior of excitable membrane and wavefront propagation in the Stomach Wall in physiological and pharmacological states. The propagation of this wave is based on cellular electrophysiological activity and ionic channel properties. In this study, we arranged the stomach wall cells together using the Gap Junctions approach. Slow wave is generated by gastric pacemaker cells. This wave propagates via the interaction of cells with each other throughout the stomach wall. Potassium currents are one of the main factors in regulating the pattern of wavefront propagation. To investigate the effect of limiting the exchange of potassium currents from cell membranes, 10%, 50%, 90%, and complete blockade were applied on both non-inactivating potassium current (IKni) and fast-inactivating potassium current (IKfi). The results show that IKniion channel blockage has a considerable effect on the plateau phase in the propagation of the excitation wave. The maximum value of the action potential in the plateau phase in the excitation wave with complete obstruction from -40.92 mV in the physiological state reached -18.97 mV, which is about 54% higher than the physiological state. Also, compared to the physiological state, complete blockage of the I_Kfi causes a 15% increase in the slow-wave spike phase (from -36.72 mV to -31.36 mV). Using this model, the effect of ions in different phases of slow-wave can be investigated. In addition, by blocking ion channels, functional disorders and smooth muscle contraction can be improved.

An Extended-Range Inductive Near-Field Telemetry System for High-Resolution Mapping of Gastrointestinal Activity.

We present an extended-range near-field wireless data communication designed for high-resolution mapping of gastrointestinal bioelectrical activity. The system is composed of an implantable unit (IU), a wearable unit (WU) and a stationary unit (SU). The WU transfers power to the IU and recharges its battery through an inductive link, wirelessly; and over the same link, reads the 64-channel slow waves data encoded by a differential pulse position coding algorithm, which is modulated through a load shift-keying technique and sent by a back-telemetry circuit at the IU. To guarantee simultaneous WU-IU wireless power transfer and maximize the IU-WU data transfer rate, the duty cycle of the data stream is reduced to 6.25%. A newly designed 13.56 MHz high-power radio frequency power amplifier at the WU, extends the efficient range of IU-WU near-field data communication and power transfer. The retrieved data at the WU are either transmitted to the SU via a 2.4 GHz RF link for real-time monitoring or stored locally on a memory card. The measurements on the implemented system, demonstrate IU-WU data transfer rate of 125 kb/s, while the distance between the transmitter and receiver coils can reach up to 7 cm while maintaining the specific absorption rate below the guidelines.

An Implantable Inductive Near-Field Communication System with 64 Channels for Acquisition of Gastrointestinal Bioelectrical Activity.

High-resolution (HR) mapping of the gastrointestinal (GI) bioelectrical activity is an emerging method to define the GI dysrhythmias such as gastroparesis and functional dyspepsia. Currently, there is no solution available to conduct HR mapping in long-term studies. We have developed an implantable 64-channel closed-loop near-field communication system for real-time monitoring of gastric electrical activity. The system is composed of an implantable unit (IU), a wearable unit (WU), and a stationary unit (SU) connected to a computer. Simultaneous data telemetry and power transfer between the IU and WU is carried out through a radio-frequency identification (RFID) link operating at 13.56 MHz. Data at the IU are encoded according to a self-clocking differential pulse position algorithm, and load shift keying modulated with only 6.25% duty cycle to be back scattered to the WU over the inductive path. The retrieved data at the WU are then either transmitted to the SU for real-time monitoring through an ISM-band RF transceiver or stored locally on a micro SD memory card. The measurement results demonstrated successful data communication at the rate of 125 kb/s when the distance between the IU and WU is less than 5 cm. The signals recorded in vitro at IU and received by SU were verified by a graphical user interface.

Monitoring and Modulating the Gastrointestinal Activity: A Wirelessly Programmable System with Impedance Measurement Capability.

This paper presents the development and benchtop validation of a system that can wirelessly acquire gastric electrical activity called slow-waves (SWs), modulate the gastrointestinal activity through stimulating with low- and high-power current pulses, and measure the tissue bio-impedance over the frequency range of 0.01 - 10 kHz. The developed system is composed of a front-end unit, and a back-end unit connected to a computer. A graphical user interface was designed in LabVIEW to process and display the recorded SWs and measured bio-impedance in real time and to configure the stimulation pulses, wirelessly. Bench-top validation showed an appropriate frequency response for analog conditioning and digitization resolution to acquire SWs. Moreover, the system was able to deliver electrical pulses at amplitudes up to ±10 mA to a maximum load of 1 kΩ. After in vivo studies, the system will be used to diagnose and treat functional gastrointestinal disorders.

A High-Resolution Wireless Power Transfer and Data Communication System for Studying Gastric Slow Waves.

We present a wireless recording system designed for high-resolution mapping of gastric slow-wave signals. The system is composed of an implantable unit (IU), a wearable unit (WU), and a stationary unit (SU) connected to a computer. Two independent wireless data communication links consisting of IU-WU and IU-SU were developed based on near-field and far-field communication, respectively. Furthermore, the WU is capable to wirelessly recharge the IU's battery through an inductive link. For the IU-WU near-field communication, a differential pulse position data encoding algorithm with only 6.25% duty cycle, with load shift keying (LSK) modulation is developed to guarantee continuous power transmission and high data transfer rate, simultaneously. The IU sends the encoded data to the WU, and the WU can either store the data locally on a memory card or transmit them to the SU for real-time monitoring. In addition, the IU-SU far-field data communication was developed based on a RF transceiver in which the IU transmits the data directly to the SU. The benchtop validation of the system demonstrated successful IU-WU and WU-SU data transmission, while sample signals were recorded successfully at IU through saline solution and received by SU.

An Ultrasonically Powered Wireless System for In Vivo Gastric Slow-Wave Recording.

This paper summarizes our recent progress towards Gastric Seed which is an ultrasonically interrogated millimeter-sized implant for gastric electrical activity (also known as slow waves, SWs) recording. We present a proof-of-concept wireless system designed to collect, transmit, and store in vivo SW signals by integrating a prototype Gastric Seed chip, fabricated in a 0.35-µm 2P4M CMOS process, with a commercial-off-the-shelf (COTS) amplifier, 10-bit analog-to-digital converter (ADC), and pair of microcontrollers (MCU) as radio-frequency (RF) transceivers. The chip includes ultrasonic self-regulated power management and addressable pulse-based data transfer. Utilizing two pairs of millimeter-sized stacked power/data ultrasonic transducers spaced by 6 cm in a water tank, the chip achieved a regulated voltage of 2.5 V and a data rate of 16 kbps. The amplifier was configured to have a gain of 60 dB with a 3-dB bandwidth of 18 mHz to 500 mHz. The MCU's built-in 10-bit ADC and RF transceiver were used to digitize the SW signal and transmit the data to a computer. In vivo, SW was recorded wirelessly from the stomach of an anesthetized rat. The recorded SWs showed a frequency of 1.5 cycle-per-minute (cpm) and maximum and minimum amplitudes of 1.03 mV and 0.28 mV peak-to-peak, respectively.

Use of Bioelectronics in the Gastrointestinal Tract.

Gastrointestinal (GI) motility disorders are major contributing factors to functional GI diseases that account for >40% of patients seen in gastroenterology clinics and affect >20% of the general population. The autonomic and enteric nervous systems and the muscles within the luminal GI tract have key roles in motility. In health, this complex integrated system works seamlessly to transport liquid, solid, and gas through the GI tract. However, major and minor motility disorders occur when these systems fail. Common functional GI motility disorders include dysphagia, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, postoperative ileus, irritable bowel syndrome, functional diarrhea, functional constipation, and fecal incontinence. Although still in its infancy, bioelectronic therapy in the GI tract holds great promise through the targeted stimulation of nerves and muscles.

A 32-Channel Wireless Configurable System for Electrical Stimulation of the Stomach.

We have designed and developed a configurable system that can generate and deliver a variety of electrical pulses suitable for gastrointestinal studies. The system is composed of a front-end unit, and a back-end unit that is connected to a computer. The front-end unit contains a stimulating module with 32 channels configured to generate two different current pulses, simultaneously. Commercial off-the-shelf components were used to develop front- and back-end units. A graphical user interface was designed in LabVIEW that allows configuration of the stimulation pulses through the back-end unit in real-time. The system was successfully validated on bench top. The bench-top studies showed the capability of the system to deliver bipolar, monopolar and unbalanced electrical pulses to a maximum load of 1.5 kΩ, at amplitudes up to ±10 mA with resolution of 10 µA, and pulse widths varying between 80 µs to 60 s with the resolution of 80 µs. This study reports the first multi-channel bipolar stimulator that is designed for gastrointestinal studies, and can be configured wirelessly. The system can be used for treating functional gastrointestinal disorders in future.

A Configurable Portable System for Ambulatory Monitoring of Gastric Bioelectrical Activity and Delivering Electrical Stimulation.

The purpose of this paper is to develop and validate a configurable system that can wirelessly acquire gastric electrical activity called slow waves, and deliver high energy electrical pulses to modulate its activity. The system is composed of a front-end unit, and an external stationary backend unit that is connected to a computer. The front-end unit contains a recording module with four channels, and a stimulating module with two channels. Commercial off-theshelf components were used to develop front- and back-end units. A graphical user interface (GUI) was designed in LabVIEW to process and display the recorded data in realtime, and store the data for off-line analysis. Besides, the gain of the analog conditioning circuit as well as the stimulation pulse configuration is programmable directly through the GUI. The system was successfully validated on bench top. The benchtop studies showed an appropriate frequency response for analog conditioning and digitization resolution to acquire gastric slow waves. Moreover, the system was able to deliver electrical pulses at amplitudes up to ±24 mA and ±12 mA to a load of up to 0.5 k $\Omega $ and 1 $\textbf{k}\Omega $, respectively. This study reports the first high-energy stimulator that can be controlled wirelessly and integrated into a gastric bioelectrical activity monitoring system. The system can be used for treating functional gastrointestinal disorders.

Bioelectronics for mapping gut activity.

Gastric peristalsis is initiated and coordinated by an underlying bioelectrical activity, termed slow waves. High-resolution (HR) mapping of the slow waves has become a fundamental tool for accurately defining electrophysiological properties in gastroenterology, including dysrhythmias in gastric disorders such as gastroparesis and functional dyspepsia. Currently, HR mapping is achieved via acquisition of slow waves taken directly from the serosa of fasted subjects undergoing invasive abdominal surgery. Recently, a minimally invasive retractable catheter and electrode has been developed for HR mapping that can only be used in short-term studies in subjects undergoing laparoscopy. Noninvasive mapping has also emerged from multichannel cutaneous electrogastrography; however, it lacks sufficient resolution and is prone to artifacts. Bioelectronics that can map slow waves in conscious subjects, postprandially and long-term, are in high demand. Due to the low signal-to-noise ratio of cutaneous electrogastrography, electrodes for HR mapping of gut activity have to acquire slow waves directly from the gut; hence, development of novel device implantation methods has inevitably accompanied development of the devices themselves. Initial efforts that have paved the way toward achieving these goals have included development of miniature wireless systems with a limited number of acquisition channels using commercially available off-the-shelf electronic components, flexible HR electrodes, and endoscopic methods for minimally invasive device implantation. To further increase the spatial resolution of HR mapping, and to minimize the size and power consumption of the implant for long-term studies, application-specific integrated circuitry, wireless power transfer, and stretchable electronics technologies have had to be integrated into a single system.

A Miniature Configurable Wireless System for Recording Gastric Electrophysiological Activity and Delivering High-Energy Electrical Stimulation.

The purpose of this paper is to develop and validate a miniature system that can wirelessly acquire gastric electrical activity called slow waves, and deliver high energy electrical pulses to modulate its activity. The system is composed of a front-end unit, and an external stationary back-end unit that is connected to a computer. The front-end unit contains a recording module with three channels, and a single-channel stimulation module. Commercial off-the-shelf components were used to develop front- and back-end units. A graphical user interface was designed in LabVIEW to process and display the recorded data in real-time, and store the data for off-line analysis. The system was successfully validated on bench top and in vivo in porcine models. The bench-top studies showed an appropriate frequency response for analog conditioning and digitization resolution to acquire gastric slow waves. The system was able to deliver electrical pulses at amplitudes up to 10 mA to a load smaller than 880 Ω. Simultaneous acquisition of the slow waves from all three channels was demonstrated in vivo. The system was able to modulate -by either suppressing or entraining- the slow wave activity. This study reports the first high-energy stimulator that can be controlled wirelessly and integrated into a gastric bioelectrical activity monitoring system. The system can be used for treating functional gastrointestinal disorders.

Electromagnetic interference in intraoperative monitoring of motor evoked potentials and a wireless solution.

Intraoperative neurophysiological monitoring (IONM) is utilized to minimize neurological morbidity during spine surgery. Transcranial motor evoked potentials (TcMEPs) are principal IONM signals in which the motor cortex of the subject is stimulated with electrical pulses and the evoked potentials are recorded from the muscles of interest. Currently available monitoring systems require the connection of 40-60 lengthy lead wires to the patient. These wires contribute to a crowded and cluttered surgical environment, and limit the maneuverability of the surgical team. In this work, it was demonstrated that the cumbersome wired system is vulnerable to electromagnetic interference (EMI) produced by operating room (OR) equipment. It was hypothesized that eliminating the lengthy recording wires can remove the EMI induced in the IONM signals. Hence, a wireless system to acquire TcMEPs was developed and validated through bench-top and animal experiments. Side-by-side TcMEPs acquisition from the wired and wireless systems in animal experiments under controlled conditions (absence of EMI from OR equipment) showed comparable magnitudes and waveforms, thus demonstrating the fidelity in the signal acquisition of the wireless solution. The robustness of the wireless system to minimize EMI was compared with a wired-system under identical conditions. Unlike the wired-system, the wireless system was not influenced by the electromagnetic waves from the C-Arm X-ray machine and temperature management system in the OR.

A 32-channel wireless system for recording gastric electrical activity.

This paper presents a wireless system designed to collect, store and transmit gastric electrical activity, known as slow waves. The system is composed of a miniaturized front-end module that can record from up to 32 locations of the stomach, and a back-end module. The front-end could either store the recorded slow waves into a flash memory, or wirelessly transmit them to the back-end connected to a computer featuring a custom-made graphical user interface (GUI). The GUI displays signals in real time, and stores them for off-line analysis. The front-end with the dimensions of 12×48×4 mm3, allows for potential implantation through laparoscopic or endoscopic procedure. The system was successfully tested on rigorous bench-top experiments. The results of these tests showed that the system could run as designed and accurately map the signals collected by each sensor, as well as show that the flash memory could store data for almost 34 hours should wireless communication be lost.

An inductive narrow-pulse RFID telemetry system for gastric slow waves monitoring.

We present a passive data telemetry system for real-time monitoring of gastric electrical activity of a living subject. The system is composed of three subsystems: an implantable unit (IU), a wearable unit (WU), and a stationary unit (SU). Data communication between the IU and WU is based on a radio-frequency identification (RFID) link operating at 13.56 MHz. Since wireless power transmission and reverse data telemetry system share the same inductive interface, a load shift keying (LSK)-based differential pulse position (DPP) coding data communication with only 6.25% duty cycle is developed to guarantee consistent wireless downlink power transmission and uplink high data transfer rate, simultaneously. The clock and data are encoded into one signal by an MSP430 microcontroller (MCU) at the IU side. This signal is sent to the WU through the inductive link, where decoded by an MSP432 MCU. Finally, the retrieved data at the WU are transmitted to the SU connected to a PC via a 2.4 GHz transceiver for real-time display and analysis. The results of the measurements on the implemented test bench, demonstrate IU-WU 125 kb/s and WU-SU 2 Mb/s data transmission rate with no observed mismatch, while the data stream was randomly generated, and matching between the transmitted data by the IU and received by the SU verified by a custom-made automated software.

Towards a highly-scalable wireless implantable system-on-a-chip for gastric electrophysiology.

This paper presents the system design of a highly-scalable system-on-a-chip (SoC) to wirelessly and chronically detect the mechanisms underlying gastric dysrhythmias. The proposed wireless implantable gastric-wave recording (WIGR) SoC records gastric slow-wave and spike activities from 256 sites, and establishes transcutaneous data communication with an external reader while being inductively powered. The SoC is highly scalable by employing a modular architecture for the analog front-end (AFE), a near-field pulse-delay modulation (PDM) data transmitter (Tx) that its data rate is proportional to the power carrier frequency (fp), and an adaptive power management equipped with automatic-resonance tuning (ART) that dynamically compensates for environmental and fp variations of the implant power coil. The simulation and measurement results for individual blocks have been presented.

An interoperable pillbox system for smart medication adherence.

We have designed and fabricated an interoperable system for medication adherence. The system is composed of a pillbox that wirelessly communicates with a computer application and a custom-made wristband. The system receives the information of taking specific medication from the user or caregiver, reminds the user to take the medication, monitors the user's hand gesture during the medication intake and monitors the compartments of the pillbox for refilling purpose. The performance of the developed system was examined in various bench-top scenarios. The system has the potential to improve the existing systems by reminding the user to take the medication through the wristband, automatically collecting user's hand gestures during the medication intake, and providing detailed information about the exisexistencetence of medication in the compartments of the pillbox.

Automatic identification of solid-phase medication intake using wireless wearable accelerometers.

We have proposed a novel solution to a fundamental problem encountered in implementing non-ingestion based medical adherence monitoring systems, namely, how to reliably identify pill medication intake. We show how wireless wearable devices with tri-axial accelerometer can be used to detect and classify hand gestures of users during solid-phase medication intake. Two devices were worn on the wrists of each user. Users were asked to perform two activities in the way that is natural and most comfortable to them: (1) taking empty gelatin capsules with water, and (2) drinking water and wiping mouth. 25 users participated in this study. The signals obtained from the devices were filtered and the patterns were identified using dynamic time warping algorithm. Using hand gesture signals, we achieved 84.17 percent true positive rate and 13.33 percent false alarm rate, thus demonstrating that the hand gestures could be used to effectively identify pill taking activity.

Objective quantification of upper extremity motor functions in Unified Parkinson's Disease Rating Scale Test.

Two tri-axial accelerometers were placed on the wrists (one on each hand) of the patients with Parkinson's disease (PD) and a non-PD control group. Subjects were asked to perform three of the upper extremity motor function tasks from the Unified Parkinson's Disease Rating Scale (UPDRS) test. The tasks were: 1) finger tapping, 2) opening and closing of palms, and 3) pronation-supination movements of the forearms. The inertia signals were wirelessly received and stored on a computer for further off-line analysis. Various features such as range, standard deviation, entropy, time to accomplish the task, and maximum frequency present in the signal were extracted and compared. The results showed that among the studied population, "standard deviation", "range", "entropy", "time" and "max frequency" are the best to worst features, respectively, to distinguish between the non-PD and PD subjects. Furthermore, using the mentioned features, it is more probable to distinguish between the non-PD and PD subjects from tasks 2 and 3 as opposed to task 1.