Slow Wave Propagation Patterns Research Articles

Gastric slow-wave modulation via power-controlled, irrigated radio-frequency ablation.

Recently, radio-frequency ablation has been used to modulate slow-wave activity in the porcine stomach. Gastric ablation is, however, still in its infancy compared to its history in the cardiac field, and electrophysiological studies have been restricted to temperature-controlled, non-irrigated ablation. Power-controlled, irrigated ablation may improve lesion formation at lower catheter-tip temperatures that produce the desired localized conduction block. Power-controlled, irrigated radio-frequency ablation was performed on the gastric serosal surface of female weaner pigs (n = 5) invivo. Three combinations of power (10-15 W) and irrigation settings (2-5 mL min-1) were investigated. A total of 12 linear lesions were created (n = 4 for each combination). Slow waves were recorded before and after ablation using high-resolution electrical mapping. Irrigation maintained catheter-tip temperature below 50°C. Ablation induced a complete conduction block in 8/12 cases (4/4 for 10 W at 2 mL min-1, 1/4 for 10 W at 5 mL min-1, 3/4 for 15 W at 5 mL min-1). Blocks were characterized by a decrease in signal amplitude at the lesion site, along with changes in slow-wave propagation patterns, where slow waves terminated at and/or rotated around the edge of the lesion. Power-controlled, irrigated ablation can successfully modulate gastric slow-wave activity at a reduced catheter-tip temperature compared to temperature-controlled, non-irrigated ablation. Reducing the irrigation rate is more effective than increasing power for blocking slow-wave activity. These benefits suggest that irrigated ablation is a suitable option for further translation into a clinical intervention for gastric electrophysiology disorders.

High-energy pacing inhibits slow-wave dysrhythmias in the small intestine.

The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.

Measurement and Analysis of In Vivo Gastroduodenal Slow Wave Patterns Using Anatomically-Specific Cradles and Electrodes.

Bioelectrical 'slow waves' regulate gastrointestinal contractions. We aimed to confirm whether the pyloric sphincter demarcates slow waves in the intact stomach and duodenum. We developed and validated novel anatomically-specific electrode cradles and analysis techniques which enable high-resolution slow wave mapping across the in vivo gastroduodenal junction. Cradles housed flexible-printed-circuit and custom cradle-specific electrode arrays during acute porcine experiments (N = 9; 44.92 kg ± 8.49 kg) and maintained electrode contact with the gastroduodenal serosa. Simultaneous gastric and duodenal slow waves were filtered independently after determining suitable organ-specific filters. Validated algorithms calculated slow wave propagation patterns and quantitative descriptions. Butterworth filters, with cut-off frequencies (0.0167 - 2) Hz and (0.167 - 3.33) Hz, were optimal filters for gastric and intestinal slow wave signals, respectively. Antral slow waves had a frequency of (2.76 ± 0.37) cpm, velocity of (4.83 ± 0.21) mm·s-1, and amplitude of (1.13 ± 0.24) mV, before terminating at the quiescent pylorus that was (46.54 ± 5.73) mm wide. Duodenal slow waves had a frequency of (18.13 ± 0.56) cpm, velocity of (11.66 ± 1.36) mm·s-1, amplitude of (0.32 ± 0.03) mV, and originated from a pacemaker region (7.24 ± 4.70) mm distal to the quiescent zone. Novel engineering methods enable measurement of in vivo electrical activity across the gastroduodenal junction and provide qualitative and quantitative definitions of slow wave activity. The pylorus is a clinical target for a range of gastrointestinal motility disorders and this work may inform diagnostic and treatment practices.

Robust Regression and Optimal Transport Methods to Predict Gastrointestinal Disease Etiology From High Resolution EGG and Symptom Severity.

Gastric functional and motility disorders are highly prevalent, with gastroparesis (GP) and functional dyspepsia (FD), affecting 1.5-3% and 10% of the population, respectively. Multiple disease etiologies with overlapping symptoms, such as antral hypomotility, pylorospasm, autonomic dysfunction, and gastric myoelectric dysfunction underlie GP and FD. There is an unmet need to differentiate these etiologies non-invasively to tailor treatment strategies and predict treatment response. We performed cutaneous high-resolution electrogastrogram (HR-EGG) recordings on 32 human subjects (controls, GP, and FD) and computed gastric slow wave propagation patterns. We implemented robust regression and clustering methods to identify one group of patients with symptoms well explained by spatial slow wave features and another with symptom severity significantly exceeding predictions from spatial slow wave features. Five patients were re-assessed with validated symptom questionnaires after pyloric and prokinetic interventions. A group of seven patients was identified whose spatial slow wave features lie within the same range as control subjects but whose symptom severity significantly exceeded what is predicted from spatial slow wave features. We hypothesize that gastric myoelectric dysfunction is not a prominent disease etiology in this group. A highly accurate regression holds in the other group of patients (r=0.8). Of the patients with repeat questionnaires, patients with symptom severity exceeding the regression line reported symptom improvement, whereas patients with symptoms in close proximity to the regression line experienced no improvement. These findings suggest that patients with symptom severity significantly exceeding the robust regression line have symptoms that cannot be explained by gastric myoelectric dysfunction alone, and vice versa. This methodology may provide clinicians with an opportunity to screen patients to determine when existing interventions will be effective, and on the flipside, when slow wave restoration interventions, such as gastric neuromodulation, may be most effective in improving symptoms and quality of life.

The gastric conduction system in health and disease: a translational review.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Design and Validation of a Surface-Contact Electrode for Gastric Pacing and Concurrent Slow-Wave Mapping.

Gastric contractions are, in part, coordinated by slow-waves. Functional motility disorders are correlated with abnormal slow-wave patterns. Gastric pacing has been attempted in a limited number of studies to correct gastric dysmotility. Integrated electrode arrays capable of pacing and recording slow-wave responses are required. New flexible surface-contact pacing electrodes (SPE) that can be placed atraumatically to pace and simultaneously map the slow-wave activity in the surrounding area were developed. SPE were applied in pigs in-vivo for gastric pacing along with concurrent high-resolution slow wave mapping as validation. Histology was conducted to assess for tissue damage around the pacing site. SPE were compared against temporary cardiac pacing electrodes (CPE), and hook-shaped pacing electrodes (HPE), for entrainment rate, entrainment threshold, contact quality, and slow-wave propagation patterns. Pacing with SPE (amplitude: 2 mA, pulse width: 100 ms) consistently achieved pacemaker initiation. Histological analysis illustrated no significant tissue damage. SPE resulted in a higher rate of entrainment (64%) than CPE (37%) and HPE (24%), with lower entrainment threshold (25% of CPE and 16% of HPE). High resolution mapping showed that there was no significant difference between the initiated slow-wave propagation speed for SPE and CPE (6.8±0.1 vs 6.8±0.2mm/s, P>0.05). However, SPE had higher loss of tissue lead contact quality than CPE (42±16 vs 13±10% over 20min). Pacing with SPE induced a slow-wave pacemaker site without tissue damage. SPE offered an atraumatic pacing electrode with a significant reduction of power consumption and placement time compared to impaled electrodes.

Simulation-based Analysis of Magnetogastrography Sensor Configurations for Characterizing Gastric Slow Wave Dysrhythmias.

The routine diagnosis of gastric motility disorders represents a significant problem to current clinical practice. Magnetogastrography (MGG) provides a non-invasive option for assessing gastric slow wave (SW) dysrhythmias that are associated with motility disorders. However, its ability to characterize SW propagation is impaired by the limited spatial coverage of existing superconducting quantum interference devices (SQUIDs). Recently developed optically-pumped magnetometers can potentially substitute SQUIDs and enable subject-specific MGG arrays with greater spatial coverage. This study developed simulations of gastric MGG to determine the distribution of the magnetic fields (MFs) generated by SWs above the torso, and investigated the impact of several realistic dysrhythmic patterns of propagation. The distribution of MFs was found to vary significantly for different patterns of SW propagation, with ectopic dysrhythmia displaying the greatest difference from normal. Notably, some important proportion of the MFs lay outside the coverage of an existing experimental SQUID array used in gastrointestinal research for some simulated SW propagation patterns, such as retrograde activity. Results suggest that MGG measurements should be made over the entire frontal face of the torso to capture all of the strongest MFs generated by SWs.Clinical relevance- This provides a guide for the placement of MGG sensors for the capture of both normal and dysrhythmic gastric slow wave propagation.

A novel approach for model-based design of gastric pacemakers

Understanding the slow wave propagation patterns of Interstitial Cells of Cajal (ICC) is essential when designing Gastric Electrical Stimulators (GESs) to treat motility disorders. A GES with the ability to both sense and pace, working in closed-loop with the ICC, will enable efficient modulation of Gastrointestinal (GI) dysrhythmias. However, existing GESs targeted at modulating GI dysrhythmias operate in an open-loop and hence their clinical efficacy is uncertain. This paper proposes a novel model-based approach for designing GESs that operate in closed-loop with the GI tract. GES is modelled using Hybrid Input Output Automata (HIOA), a well-known formal model, which is suitable for designing safety-critical systems. A two-dimensional ICC network working in real-time with the GES is developed using the same compositional HIOA framework. The ICC network model is used to simulate normal and diseased action potential propagation patterns akin to those observed during GI dysrhythmias. The efficacy of the proposed GES is then validated by integrating it in closed-loop with the ICC network. Results show that the proposed GES is able to sense the propagation patterns and modulate the dysrhythmic patterns of bradygastria back to its normal state automatically. The proposed design of the GES is flexible enough to treat a variety of diseased dysrhythmic patterns using closed-loop operation.

Intra-operative high-resolution mapping of slow wave propagation in the human jejunum: Feasibility and initial results.

Bioelectrical slow waves are a coordinating mechanism of small intestine motility, but extracellular human studies have been restricted to a limited number of sparse electrode recordings. High-resolution (HR) mapping has offered substantial insights into spatiotemporal intestinal slow wave dynamics, but has been limited to animal studies to date. This study aimed to translate intra-operative HR mapping to define pacemaking and conduction profiles in the human small intestine. Immediately following laparotomy, flexible-printed-circuit arrays were applied around the serosa of the proximal jejunum (128-256 electrodes; 4-5.2mm spacing; 28-59cm2 ). Slow wave propagation patterns were mapped, and frequencies, amplitudes, downstroke widths, and velocities were calculated. Pacemaking and propagation patterns were defined. Analysis comprised nine patients with mean recording duration of 7.6±2.8minutes. Slow waves occurred at a frequency of 9.8±0.4cpm, amplitude 0.3±0.04mV, downstroke width 0.5±0.1seconds, and with faster circumferential velocity than longitudinal (10.1±0.8 vs 9.0±0.7mm/s; P=.001). Focal pacemakers were identified and mapped (n=4; mean frequency 9.9±0.2cpm). Disordered slow wave propagation was observed, including wavefront collisions, conduction blocks, and breakout and entrainment of pacemakers. This study introduces HR mapping of human intestinal slow waves, and provides first descriptions of intestinal pacemaker sites and velocity anisotropy. Future translation to other intestinal regions, disease states, and postsurgical dysmotility holds potential for improving the basic and clinical understanding of small intestine pathophysiology.

A novel retractable laparoscopic device for mapping gastrointestinal slow wave propagation patterns.

Gastric slow waves regulate peristalsis, and gastric dysrhythmias have been implicated in functional motility disorders. To accurately define slow wave patterns, it is currently necessary to collect high-resolution serosal recordings during open surgery. We therefore developed a novel gastric slow wave mapping device for use during laparoscopic procedures. The device consists of a retractable catheter constructed of a flexible nitinol core coated with Pebax. Once deployed through a 5-mm laparoscopic port, the spiral head is revealed with 32 electrodes at 5mm intervals. Recordings were validated against a reference electrode array in pigs and tested in a human patient. Recordings from the device and a reference array in pigs were identical in frequency (2.6 cycles per minute; p=0.91), and activation patterns and velocities were consistent (8.9±0.2 vs 8.7±0.1mms-1; p=0.2). Device and reference amplitudes were comparable (1.3±0.1 vs 1.4±0.1mV; p=0.4), though the device signal-to-noise ratio was higher (17.5±0.6 vs 12.8±0.6dB; P<0.0001). In the human patient, corpus slow waves were recorded and mapped (frequency 2.7±0.03cycles per minute, amplitude 0.8±0.4mV, velocity 2.3±0.9mms-1). In conclusion, the novel laparoscopic device achieves high-quality serosal slow wave recordings. It can be used for laparoscopic diagnostic studies to document slow wave patterns in patients with gastric motility disorders.

Automated Classification and Identification of Slow Wave Propagation Patterns in Gastric Dysrhythmia

The advent of high-resolution (HR) electrical mapping of slow wave activity has significantly improved the understanding of gastric slow wave activity in normal and dysrhythmic states. One of the current limitations of this technique is it generates a vast amount of data, making manual analysis a tedious task for research and clinical development. In this study we present new automated methods to classify, identify, and locate patterns of interest in gastric slow wave propagation. The classification method uses a similarity metric to classify slow wave propagations, while the identification algorithm uses the divergence and mean curvature of the slow wave propagation to identify and regionalize patterns of interest. The methods were applied to synthetic and experimental datasets and were also compared to manual analysis. The methods classified and identified patterns of slow wave propagation in less than 1 s, compared to manual analysis which took up to 40 min. The automated methods achieved 96% accuracy in classifying AT maps, and 95% accuracy in identifying the propagation pattern with a mean spatial error of 1.5 mm in comparison to manual methods. These new methods will facilitate the efficient translation of gastrointestinal HR mapping techniques to clinical practice.

Experimental and Automated Analysis Techniques for High-resolution Electrical Mapping of Small Intestine Slow Wave Activity

Background/AimsSmall intestine motility is governed by an electrical slow wave activity, and abnormal slow wave events have been associated with intestinal dysmotility. High-resolution (HR) techniques are necessary to analyze slow wave propagation, but progress has been limited by few available electrode options and laborious manual analysis. This study presents novel methods for in vivo HR mapping of small intestine slow wave activity.MethodsRecordings were obtained from along the porcine small intestine using flexible printed circuit board arrays (256 electrodes; 4 mm spacing). Filtering options were compared, and analysis was automated through adaptations of the falling-edge variable-threshold (FEVT) algorithm and graphical visualization tools.ResultsA Savitzky-Golay filter was chosen with polynomial-order 9 and window size 1.7 seconds, which maintained 94% of slow wave amplitude, 57% of gradient and achieved a noise correction ratio of 0.083. Optimized FEVT parameters achieved 87% sensitivity and 90% positive-predictive value. Automated activation mapping and animation successfully revealed slow wave propagation patterns, and frequency, velocity, and amplitude were calculated and compared at 5 locations along the intestine (16.4 ± 0.3 cpm, 13.4 ± 1.7 mm/sec, and 43 ± 6 µV, respectively, in the proximal jejunum).ConclusionsThe methods developed and validated here will greatly assist small intestine HR mapping, and will enable experimental and translational work to evaluate small intestine motility in health and disease.

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

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. 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. 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. 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.