Optimization of Gastric Pacing Parameters Using High-Resolution Mapping.

OBJECTIVE: Abnormal slow-wave activity has been associated with functional motility disorders. Gastric pacing has been investigated to correct slow-wave abnormalities, but clinical therapies are yet to be established. This study aimed to define optimal parameters to advance the application of gastric pacing. METHODS: High-resolution gastric mapping was utilized to evaluate four pacing parameters in in-vivo pig studies: (i) orientation of the pacing electrodes (longitudinal vs circumferential), (ii) pacing energy (900 vs 10,000 ms mA2), (iii) the pacing location (corpus vs antrum), and (iv) pacing period (between 12 and 36 s). RESULTS: The probability of slow-wave initiation and entrainment with the pacing electrodes oriented longitudinally was significantly higher than with electrodes orientated circumferentially (86 vs 10%). High-energy pacing accelerated entrainment over the entire mapped field compared to low-energy pacing (3.1±1.5 vs 7.3±2.4 impulses, p < 0.001). Regardless of the location of the pacing site, the new site of slow-wave initiation was always located 4-12 mm away from the pacing site, between the greater curvature and negative pacing electrode. A pacing period between 14-30 s resulted in stable slow-wave initiation and entrainment. CONCLUSION: These data will now inform effective application of gastric pacing in future studies, including human translation.

Design of a closed-loop gastric pacemaker for modulating dysrhythmic conduction patterns via extracellular potentials.

A potential treatment option for chronic and severe motility disorders such as gastroparesis is the implantation of a Gastric Electrical Stimulator (GES), which is designed to modulate the bio-electric slow waves. However, the effectiveness of current GESs remains uncertain since they do not work in a closed-loop by sensing, processing, and modulating the dysrhythmic patterns. This work presents the design of a GES model working in closed-loop with the network of the Interstitial Cells of Cajal (ICC). A pre-existing two-dimensional ICC network is enhanced by proposing an extracellular potential generation model, which can precisely capture the timing behaviour of slow wave propagation pattern of the simulated ICC network. The GES senses the extracellular potential, detects bradygastric patterns and finally modulates the activity to ensure normal conduction. The GES is designed to be practical for ease of validation and implementation.

HD-EMG Electrode Count and Feature Selection Influence on Pattern-based Movement Classification Accuracy.

Control schemes that rely on electromyography (EMG) pattern classification have shown to improve their accuracy when coupled with an increasing number of electrodes. In this study, HD-EMG signals from the hand and forearm of volunteers performing a series of movements were recorded. Different amounts of input EMG channels were selected and time-domain features were extracted to train several SVM classifiers. Detailed comparisons were made to evaluate the impact of electrode count and feature selection over the overall classification accuracy of 17 different movements. The increased resolution achieved from higher electrode counts yielded significant improvements in classification accuracy; however, these improvements were marginal when the number of channels utilized surpassed 100 electrodes.Clinical relevance- Pattern-based EMG classification is a widely used control method for a range of prosthetic devices and robotic interfaces. This work studies the optimal number of simultaneous HD-EMG channels and features that must be considered for accurate myoelectric control using this method.

Effect of Segmentation Parameters on Classification Accuracy of High-Density EMG recordings.

Electromyography (EMG) based control systems rely on the accurate identification of patterns extracted from signal features to predict the corresponding movement. The selection of segmentation window parameters and their impact on overall accuracy of classifiers has been previously studied for systems with a low number of EMG channels (<; 16). In this study a High-density EMG electrode array was used to evaluate the impact of the parameters when a high number of channels (128) was recorded. Findings show that in combination with high channel counts the impact of window length and overlap were marginal (<; 2% and <; 1% respectively). The number of channels was found to have direct correlation with achieved accuracy, with an improvement of up to 19.5 ± 4.5% in classification accuracy when increasing from 4 to 128 channels.

Relationships between gastric slow wave frequency, velocity, and extracellular amplitude studied by a joint experimental-theoretical approach.

BACKGROUND: Gastric slow wave dysrhythmias are accompanied by deviations in frequency, velocity, and extracellular amplitude, but the inherent association between these parameters in normal activity still requires clarification. This study quantified these associations using a joint experimental-theoretical approach. METHODS: Gastric pacing was conducted in pigs with simultaneous high-resolution slow wave mapping (32-256 electrodes; 4-7.6 mm spacing). Relationships between period, velocity, and amplitude were quantified and correlated for each wavefront. Human data from two existing mapping control cohorts were analyzed to extract and correlate these same parameters. A validated biophysically based ICC model was also applied in silico to quantify velocity-period relationships during entrainment simulations and velocity-amplitude relationships from membrane potential equations. KEY RESULTS: Porcine pacing studies identified positive correlations for velocity-period (0.13 mm s-1 per 1 s, r2 =.63, P<.001) and amplitude-velocity (74 µV per 1 mm s-1 , r2 =.21, P=.002). In humans, positive correlations were also quantified for velocity-period (corpus: 0.11 mm s-1 per 1 s, r2 =.16, P<.001; antrum: 0.23 mm s-1 per 1 s, r2 =.55; P<.001), and amplitude-velocity (94 µV per 1 mm s-1 , r2 =.56; P<.001). Entrainment simulations matched the experimental velocity-period relationships and demonstrated dependence on the slow wave recovery phase. Simulated membrane potential relationships were close to these experimental results (100 µV per 1 mm s-1 ). CONCLUSIONS AND INFERENCES: These data quantify the relationships between slow wave frequency, velocity, and extracellular amplitude. The results from both human and porcine studies were in keeping with biophysical models, demonstrating concordance with ICC biophysics. These relationships are important in the regulation of gastric motility and will help to guide interpretations of dysrhythmias.

High-resolution mapping of gastric slow-wave recovery profiles: biophysical model, methodology, and demonstration of applications.

Slow waves play a central role in coordinating gastric motor activity. High-resolution mapping of extracellular potentials from the stomach provides spatiotemporal detail on normal and dysrhythmic slow-wave patterns. All mapping studies to date have focused exclusively on tissue activation; however, the recovery phase contains vital information on repolarization heterogeneity, the excitable gap, and refractory tail interactions but has not been investigated. Here, we report a method to identify the recovery phase in slow-wave mapping data. We first developed a mathematical model of unipolar extracellular potentials that result from slow-wave propagation. These simulations showed that tissue repolarization in such a signal is defined by the steepest upstroke beyond the activation phase (activation was defined by accepted convention as the steepest downstroke). Next, we mapped slow-wave propagation in anesthetized pigs by recording unipolar extracellular potentials from a high-resolution array of electrodes on the serosal surface. Following the simulation result, a wavelet transform technique was applied to detect repolarization in each signal by finding the maximum positive slope beyond activation. Activation-recovery (ARi) and recovery-activation (RAi) intervals were then computed. We hypothesized that these measurements of recovery profile would differ for slow waves recorded during normal and spatially dysrhythmic propagation. We found that the ARi of normal activity was greater than dysrhythmic activity (5.1 ± 0.8 vs. 3.8 ± 0.7 s; P < 0.05), whereas RAi was lower (9.7 ± 1.3 vs. 12.2 ± 2.5 s; P < 0.05). During normal propagation, RAi and ARi were linearly related with negative unit slope indicating entrainment of the entire mapped region. This relationship was weakened during dysrhythmia (slope: -0.96 ± 0.2 vs -0.71 ± 0.3; P < 0.05).NEW & NOTEWORTHY The theoretical basis of the extracellular gastric slow-wave recovery phase was defined using mathematical modeling. A novel technique utilizing the wavelet transform was developed and validated to detect the extracellular slow-wave recovery phase. In dysrhythmic wavefronts, the activation-to-recovery interval (ARi) was shorter and recovery-to-activation interval (RAi) was longer compared with normal wavefronts. During normal activation, RAi vs. ARi had a slope of -1, whereas the weakening of the slope indicated a dysrhythmic propagation.

High-resolution electrical mapping of porcine gastric slow-wave propagation from the mucosal surface.

BACKGROUND: Gastric motility is coordinated by bioelectrical slow waves, and gastric dysrhythmias are reported in motility disorders. High-resolution (HR) mapping has advanced the accurate assessment of gastric dysrhythmias, offering promise as a diagnostic technique. However, HR mapping has been restricted to invasive surgical serosal access. This study investigates the feasibility of HR mapping from the gastric mucosal surface. METHODS: Experiments were conducted in vivo in 14 weaner pigs. Reference serosal recordings were performed with flexible-printed-circuit (FPC) arrays (128-192 electrodes). Mucosal recordings were performed by two methods: (i) FPC array aligned directly opposite the serosal array, and (ii) cardiac mapping catheter modified for gastric mucosal recordings. Slow-wave propagation and morphology characteristics were quantified and compared between simultaneous serosal and mucosal recordings. KEY RESULTS: Slow-wave activity was consistently recorded from the mucosal surface from both electrode arrays. Mucosally recorded slow-wave propagation was consistent with reference serosal activation pattern, frequency (P≥.3), and velocity (P≥.4). However, mucosally recorded slow-wave morphology exhibited reduced amplitude (65-72% reduced, P<.001) and wider downstroke width (18-31% wider, P≤.02), compared to serosal data. Dysrhythmias were successfully mapped and classified from the mucosal surface, accorded with serosal data, and were consistent with known dysrhythmic mechanisms in the porcine model. CONCLUSIONS & INFERENCES: High-resolution gastric electrical mapping was achieved from the mucosal surface, and demonstrated consistent propagation characteristics with serosal data. However, mucosal signal morphology was attenuated, demonstrating necessity for optimized electrode designs and analytical algorithms. This study demonstrates feasibility of endoscopic HR mapping, providing a foundation for advancement of minimally invasive spatiotemporal gastric mapping as a clinical and scientific tool.

Multi-channel wireless mapping of gastrointestinal serosal slow wave propagation.

BACKGROUND: High-resolution (HR) extracellular mapping allows accurate profiling of normal and dysrhythmic slow wave patterns. A current limitation is that cables traverse the abdominal wall or a natural orifice, risking discomfort, dislodgement or infection. Wireless approaches offer advantages, but a multi-channel system is required, capable of recording slow waves and mapping propagation with high fidelity. METHODS: A novel multi-channel (n = 7) wireless mapping system was developed and compared to a wired commercial system. Slow wave signals were recorded from the porcine gastric and intestinal serosa in vivo. Signals were simultaneously acquired using both systems, and were filtered and processed to map activation wavefronts. For validation, the frequency and amplitude of detected events were compared, together with the speed and direction of mapped wavefronts. KEY RESULTS: The wireless device achieved comparable signal quality to the reference device, and slow wave frequencies were identical. Amplitudes of the acquired gastric and intestinal slow wave signals were consistent between the devices. During normal propagation, spatiotemporal mapping remained accurate in the wireless system, however, during ectopic dysrhythmic pacemaking, the lower sampling resolution of the wireless device led to reduced accuracy in spatiotemporal mapping. CONCLUSIONS & INFERENCES: A novel multichannel wireless device is presented for mapping slow wave activity. The device achieved high quality signals, and has the potential to facilitate chronic monitoring studies and clinical translation of spatiotemporal mapping. The current implementation may be applied to detect normal patterns and dysrhythmia onset, but HR mapping with finely spaced arrays currently remains necessary to accurately define dysrhythmic patterns.

Circumferential and functional re-entry of in vivo slow-wave activity in the porcine small intestine.

BACKGROUND: Slow-waves modulate the pattern of small intestine contractions. However, the large-scale spatial organization of intestinal slow-wave pacesetting remains uncertain because most previous studies have had limited resolution. This study applied high-resolution (HR) mapping to evaluate intestinal pacesetting mechanisms and propagation patterns in vivo. METHODS: HR serosal mapping was performed in anesthetized pigs using flexible arrays (256 electrodes; 32 × 8; 4 mm spacing), applied along the jejunum. Slow-wave propagation patterns, frequencies, and velocities were calculated. Slow-wave initiation sources were identified and analyzed by animation and isochronal activation mapping. KEY RESULTS: Analysis comprised 32 recordings from nine pigs (mean duration 5.1 ± 3.9 min). Slow-wave propagation was analyzed, and a total of 26 sources of slow-wave initiation were observed and classified as focal pacemakers (31%), sites of functional re-entry (23%) and circumferential re-entry (35%), or indeterminate sources (11%). The mean frequencies of circumferential and functional re-entry were similar (17.0 ± 0.3 vs 17.2 ± 0.4 cycle min(-1) ; P = 0.5), and greater than that of focal pacemakers (12.7 ± 0.8 cycle min(-1) ; P < 0.001). Velocity was anisotropic (12.9 ± 0.7 mm s(-1) circumferential vs 9.0 ± 0.7 mm s(-1) longitudinal; P < 0.05), contributing to the onset and maintenance of re-entry. CONCLUSIONS & INFERENCES: This study has shown multiple patterns of slow-wave initiation in the jejunum of anesthetized pigs. These results constitute the first description and analysis of circumferential re-entry in the gastrointestinal tract and functional re-entry in the in vivo small intestine. Re-entry can control the direction, pattern, and frequency of slow-wave propagation, and its occurrence and functional significance merit further investigation.

Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias.

BACKGROUND: Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC-MP) and circular interstitial cells of Cajal intramuscular (ICC-IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated. METHODS: An experimental-theoretical study was performed. High-resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials. KEY RESULTS: High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s(-1) ; P = 0.004) and of higher amplitude (739 vs 528 µV; P = 0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P < 0.001). CONCLUSIONS & INFERENCES: The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks.

A comparison of gold versus silver electrode contacts for high-resolution gastric electrical mapping using flexible printed circuit board arrays.

Stomach contractions are initiated and coordinated by electrical events termed slow waves, and slow wave abnormalities contribute to gastric motility disorders. Recently, flexible printed circuit board (PCB) multi-electrode arrays were introduced, facilitating high-resolution mapping of slow wave activity in humans. However PCBs with gold contacts have shown a moderately inferior signal quality to previous custom-built silver-wire platforms, potentially limiting analyses. This study determined if using silver instead of gold contacts improved flexible PCB performance. In a salt-bath test, modestly higher stimulus amplitudes were recorded from silver PCBs (mean 312, s.d. 89 µV) than those from gold (mean 281, s.d. 85 µV) (p < 0.001); however, the signal-to-noise ratio (SNR) was similar (p = 0.26). In eight in vivo experimental studies, involving gastric serosal recordings from five pigs, no silver versus gold differences were found in terms of slow wave amplitudes (mean 677 versus 682 µV; p = 0.91), SNR (mean 8.8 versus 8.8 dB; p = 0.94) or baseline drift (NRMS; mean 12.0 versus 12.1; p = 0.97). Under the prescribed conditions, flexible PCBs with silver or gold contacts provide comparable results in vivo, and contact material difference does not explain the performance difference between current-generation slow wave mapping platforms. Alternative explanations for this difference and the implications for electrode design are discussed.