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.

An Inductively Powered Implantable System to Study the Gastrointestinal Electrophysiology in Freely Behaving Rodents.

Chronic studies in the fasting and fed states of conscious subjects are fundamental for understanding the pathophysiological significance of functional gastrointestinal (GI) disorders and motility dysfunctions. To study the electrophysiology of the GI tract in the long term, the development of gastric implants is essential. This paper presents the development of an implantable system capable of monitoring the bioelectrical activity of the gastric system and modulating the activity in freely behaving rodents. The system consists of a miniature-sized implantable unit (IU), a stationary unit (SU) that communicates with the IU over a 2.4 GHz far-field radio frequency (RF) bidirectional link, and a charging unit (CU) that establishes an inductive 13.56 MHz near-field communication (NFC) with the IU, implementing an adaptive wireless power transfer (WPT). The CU can generate an adjustable power between +20 dBm and +30 dBm, and, in the presence of body movements and stomach motility, can deliver a constant rectified voltage to the IU. The live subject's exposure to the electromagnetic WPT in the developed system complies with the RF energy absorption restrictions for health and safety concerns. The system can be utilized to investigate the relationship between functional GI disorders and dysrhythmias in the gastric bioelectrical activity and study the potential of electroceutical therapies for motility dysfunctions in clinical settings.

A Wearable Wideband Analog Bio-Impedance Analyzer for Real-Time Monitoring of Human Physiology.

Continuous monitoring of electrophysiological activities of the human body is a significant step toward the effective prognosis, diagnosis, and management of functional disorders and cardiovascular diseases. This paper presents the development of a wireless system for the real-time acquisition of hemodynamics data and ambulatory monitoring of body composition based on electrical bio-impedance (Bio-Z) analysis. The developed system is composed of a low-power wearable unit and a stationary unit connected to a computer. The system conducts the non-radiative non-invasive Bio-Z analysis over a wide bandwidth of 1 MHz through four independent channels. The proposed analog approach detects the physiological activity by extracting the magnitude of the mixed Bio-Z signal, in real-time. A graphical user interface was designed for monitoring, analysis, and storage of the processed data. Moreover, the amplitude and frequency of the electrical excitation signals can be instructed through the user interface, wirelessly. Bench-top validation of the system demonstrated the delivery of current signals over a wide frequency range of 1 kHz - 1 MHz and peak-to-peak amplitude of up to 20 mA. Besides, the system was able to detect the magnitude of the envelope of the mixed signal with amplitude modulation depths as low as 0.1 %. Clinical Relevance- The system provides the real-time monitoring of cardiac activity and blood pulsation in human arteries. In addition, due to the configurability of the frequency and amplitude of the current injection circuit, the system is an excellent candidate to be utilized for real-time medical imaging through electrical bio-impedance tomography as well as electrical bio-impedance spectroscopy.

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.

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.

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 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.

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 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.