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. Post-glucagon 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 to 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.

Optimization of pacing parameters to entrain slow wave activity in the pig jejunum.

Pacing has been proposed as a therapy to restore function in motility disorders associated with electrical dysrhythmias. The spatial response of bioelectrical activity in the small intestine to pacing is poorly understood due to a lack of high-resolution investigations. This study systematically varied pacing parameters to determine the optimal settings for the spatial entrainment of slow wave activity in the jejunum. An electrode array was developed to allow simultaneous pacing and high-resolution mapping of the small intestine. Pacing parameters including pulse-width (50, 100 ms), pulse-amplitude (2, 4, 8 mA) and pacing electrode orientation (antegrade, retrograde, circumferential) were systematically varied and applied to the jejunum (n = 15 pigs). Pulse-amplitudes of 4 mA (p = 0.012) and 8 mA (p = 0.002) were more effective than 2 mA in achieving spatial entrainment while pulse-widths of 50 ms and 100 ms had comparable effects (p = 0.125). A pulse-width of 100 ms and a pulse-amplitude of 4 mA were determined to be most effective for slow wave entrainment when paced in the antegrade or circumferential direction with a success rate of greater than 75%. These settings can be applied in chronic studies to evaluate the long-term efficacy of pacing, a critical aspect in determining its therapeutic potential.

Electromechanical Response of Mesenteric Ischemia Defined Through Simultaneous High-Resolution Bioelectrical and Video Mapping.

Intestinal motility is governed in part by bioelectrical slow-waves and spike-bursts. Mesenteric ischemia is a substantial clinical challenge, but its electrophysiological and contractile mechanisms are not well understood. Simultaneous high-resolution bioelectrical and video mapping techniques were used to capture the changes in slow-waves, spike-bursts, and contractile activity during baseline, ischemia, and reperfusion periods. Experiments were performed on anesthetized pigs where intestinal contractions were quantified using surface strain and diameter measurements, while slow-wave and spike-bursts were quantified using frequency and amplitude. Slow-waves entrainment within the ischemic region diminished during ischemia, resulting in irregular slow-wave activity and a reduction in the frequency from 12.4 ± 3.0 cycles-per-minute (cpm) to 2.5 ± 2.7 cpm (p = 0.0006). At the end of the reperfusion period, normal slow-wave entrainment was observed at a frequency of 11.5 ± 2.9 cpm. There was an increase in spike-burst activity between the baseline and ischemia periods (1.1 ± 1.4 cpm to 8.7 ± 3.3 cpm, p = 0.0003) along with a spasm of circumferential contractions. At the end of the reperfusion period, the frequency of spike-bursts decreased to 2.7 ± 1.4 cpm, and contractions subsided. The intestine underwent tonal contraction during ischemia, with the diameter decreasing from 29.3 ± 2.6 mm to 21.2 ± 6.2 mm (p = 0.0020). At the end of the reperfusion period, the intestinal diameter increased to 27.3 ± 3.9 mm. The decrease in slow-wave activity, increase in spike-bursts, and tonal contractions can objectively identify ischemic segments in the intestine. It is anticipated that the use of electrophysiological slow-wave and spike-burst biomarkers, along with contractile measures, could identify mesenteric ischemia in surgical settings and allow an objective biomarker for successful revascularization.

High-Energy Pacing in the Jejunum Elicits Pulsatile Segmental Contractions.

OBJECTIVE: Compromised bowel function is associated with a range of motility disorders such as post-operative ileus and chronic intestinal pseudo-obstruction. Disordered or weak motility compromise the efficient movement of luminal contents necessary for digestion and nutrient absorption. This study investigated the potential of high-energy pacing to enhance contractions in the proximal jejunum of the small intestine. METHODS: Pacing pulse parameters (pulse-width: 100 ms, 200 ms, 400 ms, pulse-amplitude: 4 mA, 6 mA, 8 mA) were systematically varied in the in vivo porcine jejunum (n = 7) and the induced contractile responses were evaluated using a video mapping system. Localized segmental contractions were quantified by measuring the intestinal diameter and thereby computing the strain. The impact of pacing parameters on contractile strain was investigated. Finally, histological studies were conducted on paced tissue to assess for potential tissue damage. RESULTS: Segmental contractions were successfully induced at all pulse-settings and evaluated across 67 pacing sessions. In response to pacing, the intestine segment at the site of pacing contracted, with diameter reduced by 6-18%. Contractile response significantly increased with increasing pulse-amplitude. However, with increasing pulse-width, the increase in contractile response was significant only between 100 ms and 400 ms. Histology showed no tissue damage occurred when maximal pacing energy (pulse-amplitude = 4-8 mA, pulse-width = 400 ms, 5 minute duration) was applied. CONCLUSION: High-energy pacing induced periodic segmental contractions in response to pacing pulses and the contractile strain was proportional to the energy applied on the intestine. The ability to enhance motility through pacing may hold promising therapeutic potential for bowel disorders and awaits clinical translation. SIGNIFICANCE: Small intestine pacing elicits localized segmental contractions which increase in magnitude with increasing pulse settings. This study marks the first adaptation of video mapping techniques to track the pacing response in the small intestine.

Evaluation of Pacing Parameters to Induce Contractions in the Small Intestine.

Postoperative ileus and chronic intestinal pseudo-obstruction are intestinal motility disorders that can compromise bowel function resulting in a significant reduction in quality of life and prolonged hospital stays. While medication and nutritional support provides relief for some patients, a significant patient population remains untreated. Therefore, alternative treatment options are required. A novel framework that enables small intestine pacing and video mapping of the contractile response was developed. Pacing pulse parameters (pulse-period: 2.7, 10 s, pulse-width: 100, 400 ms, and pulse-amplitude: 4, 6, 8 mA) were systematically varied to investigate the effect of pacing on the small intestine contractility. The contractile response was quantified by computing the strain of the intestinal diameter at the pacing site. The framework was applied in vivo on porcine jejunal loops (n=4) where segmental contractions were induced in response to pacing pulses. Strain increased with increasing pulse-amplitude and pulse-width, while pacing at a period of 2.7 s elicited higher contractile strains compared to pacing at a period of 10 s at all settings (e.g., -0.18 ± 0.06 vs 0.12 ± 0.06 at 8 mA, 400 ms). For a pulse-width of 100 ms, the contractile strain continued to increase with increasing pulse-amplitude, while the induced strain was comparable for all pulse-amplitudes when paced with high pulse-width (400 ms). Therefore, pacing is an effective tool in modulating the intensity of segmental contractions.Clinical Relevance- Different pacing parameters can define contraction intensity and frequency in the small intestine. This is of therapeutic potential for treating motility disorders such as post-operative ileus and chronic intestinal pseudo-obstruction.

Clinical utility of trans-sacral magnetic stimulation-evoked sphincter potentials and high-density electromyography in pelvic floor assessment: Technical evaluation.

AIM: Faecal incontinence is common and of multifactorial aetiologies, yet current diagnostic tools are unable to assess nerve and sphincter function objectively. We developed an anorectal high-density electromyography (HD-EMG) probe to evaluate motor-evoked potentials induced via trans-sacral magnetic stimulation (TSMS). METHOD: Anorectal probes with an 8 × 8 array of electrodes spaced 1 cm apart were developed for recording HD-EMG of the external anal sphincter. These HD-EMG probes were used to map MEP amplitudes and latencies evoked via TSMS delivered through the Magstim Rapid2 (MagStim Company). Patients undergoing pelvic floor investigations were recruited for this IDEAL Stage 2a pilot study. RESULTS: Eight participants (median age 49 years; five female) were recruited. Methodological viability, safety and diagnostic workflow were established. The test was well tolerated with median discomfort scores ≤2.5/10, median pain scores ≤1/10 and no adverse events. Higher Faecal Incontinence Severity Index scores correlated with longer MEP latencies (r = 0.58, p < 0.001) and lower MEP amplitudes (r = -0.32, p = 0.046), as did St. Mark's Incontinence Scores with both MEP latencies (r = 0.49, p = 0.001) and MEP amplitudes (r = -0.47, p = 0.002). CONCLUSION: This HD-EMG probe in conjunction with TSMS presents a novel diagnostic tool for anorectal function assessment. Spatiotemporal assessment of magnetically stimulated MEPs correlated well with symptoms and offers a feasible, safe and patient-tolerable method of evaluating pudendal nerve and external anal sphincter function. Further clinical development and evaluation of these techniques is justified.

Electroanatomical mapping of the stomach with simultaneous biomagnetic measurements.

Gastric motility is coordinated by bioelectric slow waves (SWs) and dysrhythmic SW activity has been linked with motility disorders. Magnetogastrography (MGG) is the non-invasive measurement of the biomagnetic fields generated by SWs. Dysrhythmia identification using MGG is currently challenging because source models are not well developed and the impact of anatomical variation is not well understood. A novel method for the quantitative spatial co-registration of serosal SW potentials, MGG, and geometric models of anatomical structures was developed and performed on two anesthetized pigs to verify feasibility. Electrode arrays were localized using electromagnetic transmitting coils. Coil localization error for the volume where the stomach is normally located under the sensor array was assessed in a benchtop experiment, and mean error was 4.2±2.3mm and 3.6±3.3° for a coil orientation parallel to the sensor array and 6.2±5.7mm and 4.5±7.0° for a perpendicular coil orientation. Stomach geometries were reconstructed by fitting a generic stomach to up to 19 localization coils, and SW activation maps were mapped onto the reconstructed geometries using the registered positions of 128 electrodes. Normal proximal-to-distal and ectopic SW propagation patterns were recorded from the serosa and compared against the simultaneous MGG measurements. Correlations between the center-of-gravity of normalized MGG and the mean position of SW activity on the serosa were 0.36 and 0.85 for the ectopic and normal propagation patterns along the proximal-distal stomach axis, respectively. This study presents the first feasible method for the spatial co-registration of MGG, serosal SW measurements, and subject-specific anatomy. This is a significant advancement because these data enable the development and validation of novel non-invasive gastric source characterization methods.

Anaesthesia by intravenous propofol reduces the incidence of intra-operative gastric electrical slow-wave dysrhythmias compared to isoflurane.

Gastric motility is coordinated by bioelectrical slow-wave activity, and abnormal electrical dysrhythmias have been associated with nausea and vomiting. Studies have often been conducted under general anaesthesia, while the impact of general anaesthesia on slow-wave activity has not been studied. Clinical studies have shown that propofol anaesthesia reduces postoperative nausea and vomiting (PONV) compared with isoflurane, while the underlying mechanisms remain unclear. In this study, we investigated the effects of two anaesthetic drugs, intravenous (IV) propofol and volatile isoflurane, on slow-wave activity. In vivo experiments were performed in female weaner pigs (n = 24). Zolazepam and tiletamine were used to induce general anaesthesia, which was maintained using either IV propofol (n = 12) or isoflurane (n = 12). High-resolution electrical mapping of slow-wave activity was performed. Slow-wave dysrhythmias occurred less often in the propofol group, both in the duration of the recorded period that was dysrhythmic (propofol 14 ± 26%, isoflurane 43 ± 39%, P = 0.043 (Mann-Whitney U test)), and in a case-by-case basis (propofol 3/12, isoflurane 8/12, P = 0.015 (Chi-squared test)). Slow-wave amplitude was similar, while velocity and frequency were higher in the propofol group than the isoflurane group (P < 0.001 (Student's t-test)). This study presents a potential physiological biomarker linked to recent observations of reduced PONV with IV propofol. The results suggest that propofol is a more suitable anaesthetic for studying slow-wave patterns in vivo.

Quantification of the Regional Properties of Gastric Motility Using Dynamic Magnetic Resonance Images.

Goal: To quantify the regional properties of gastric motility from free-breathing dynamic MRI data. Methods: Free-breathing MRI scans were performed on 10 healthy human subjects. Motion correction was applied to reduce the respiratory effect. A stomach centerline was automatically generated and used as a reference axis. Contractions were quantified and visualized as spatio-temporal contraction maps. Gastric motility properties were reported separately for the lesser and greater curvatures in the proximal and distal regions of the stomach. Results: Motility properties varied in different regions of the stomach. The mean contraction frequencies for the lesser and greater curvatures were both 3.1±0.4 cycles per minute. The contraction speed was significantly higher on the greater curvature than the lesser curvature (3.5±0.7 vs 2.5±0.4 mm/s, p<0.001) while contraction size on both curvatures was comparable (4.9±1.2 vs 5.7±2.4 mm, p = 0.326). The mean gastric motility index was significantly higher in the distal greater curvature (28.13±18.89 mm2/s) compared to the other regions of the stomach (11.16-14.12 mm2/s). Conclusions: The results showed the effectiveness of the proposed method for visualization and quantification of motility patterns from MRI data.

Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) have recurrent lower abdominal pain, associated with altered bowel habit (diarrhea and/or constipation). As bowel habit is altered, abnormalities in colonic motility are likely to contribute; however, characterization of colonic motor patterns in patients with IBS remains poor. Utilizing fiber-optic manometry, we aimed to characterize distal colonic postprandial colon motility in diarrhea-predominant IBS. After an overnight fast, a 72-sensor (spaced at 1-cm intervals) manometry catheter was colonoscopically placed to the proximal colon, in 13 patients with IBS-D and 12 healthy adults. Recordings were taken for 2 h pre and post a 700 kcal meal. Data were analyzed with our two developed automated techniques. In both healthy adults and patients with IBS-D, the dominant frequencies of pressure waves throughout the colon are between 2 and 4 cycles per minute (cpm) and the power of these frequencies increased significantly after a meal. Although these pressure waves formed propagating contractions in both groups, the postprandial propagating contraction increase was significantly smaller in patients compared with healthy adults. In healthy adults during the meal period, retrograde propagation between 2 and 8 cpm was significantly greater than antegrade propagation at the same frequencies. This difference was not observed in IBS-D. Patients with IBS-D show reduced prevalence of the retrograde cyclic motor pattern postprandially compared with the marked prevalence in healthy adults. We hypothesize that this reduction may allow premature rectal filling, leading to postprandial urgency and diarrhea.NEW & NOTEWORTHY Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.

A novel framework for the removal of pacing artifacts from bio-electrical recordings.

BACKGROUND: Electroceuticals provide clinical solutions for a range of disorders including Parkinson's disease, cardiac arrythmias and are emerging as a potential treatment option for gastrointestinal disorders. However, pre-clinical investigations are challenged by the large stimulation artifacts registered in bio-electrical recordings. METHOD: A generalized framework capable of isolating and suppressing stimulation artifacts with minimal intervention was developed. Stimulation artifacts with different pulse-parameters in synthetic and experimental cardiac and gastrointestinal signals were detected using a Hampel filter and reconstructed using 3 methods: i) autoregression, ii) weighted mean, and iii) linear interpolation. RESULTS: Synthetic stimulation artifacts with amplitudes of 2 mV and 4 mV and pulse-widths of 50 ms, 100 ms, and 200 ms were successfully isolated and the artifact window size remained uninfluenced by the pulse-amplitude, but was influenced by pulse-width (e.g., the autoregression method resulted in an identical Root Mean Square Error (RMSE) of 1.64 mV for artifacts with 200 ms pulse-width and both 2 mV and 4 mV amplitudes). The performance of autoregression (RMSE = 1.45 ± 0.16 mV) and linear interpolation (RMSE = 1.22 ± 0.14 mV) methods were comparable and better than weighted mean (RMSE = 5.54 ± 0.56 mV) for synthetic data. However, for experimental recordings, artifact removal by autoregression was superior to both linear interpolation and weighted mean approaches in gastric, small intestinal and cardiac recordings. CONCLUSIONS: A novel signal processing framework enabled efficient analysis of bio-electrical recordings with stimulation artifacts. This will allow the bio-electrical events induced by stimulation protocols to be efficiently and systematically evaluated, resulting in improved stimulation therapies.

Spatial response of jejunal pacing defined by a novel high-resolution multielectrode array.

Gastric pacing has shown preclinical success in modulating bioelectrical slow-wave activity and has potential as a novel therapy for functional motility disorders. However, the translation of pacing techniques to the small intestine remains preliminary. This paper presents the first high-resolution framework for simultaneous pacing and response mapping of the small intestine. A novel surface-contact electrode array, capable of simultaneous pacing and high-resolution mapping of the pacing response, was developed and applied in vivo on the proximal jejunum of pigs. Pacing parameters including the input energy and pacing electrode orientation were systematically evaluated, and the efficacy of pacing was determined by analyzing spatiotemporal characteristics of entrained slow waves. Histological analysis was conducted to determine if the pacing resulted in tissue damage. A total of 54 studies were conducted on 11 pigs, and pacemaker propagation patterns were successfully achieved at both low (2 mA, 50 ms) and high (4 mA, 100 ms) energy levels with the pacing electrodes oriented in the antegrade, retrograde, and circumferential directions. The high energy level performed significantly better (P = 0.014) in achieving spatial entrainment. Comparable success (greater than 70%) was achieved when pacing in the circumferential and antegrade pacing directions, and no tissue damage was observed at the pacing sites. This study defined the spatial response of small intestine pacing in vivo revealing effective pacing parameters for slow-wave entrainment in the jejunum. Intestinal pacing now awaits translation to restore disordered slow-wave activity associated with motility disorders.NEW & NOTEWORTHY A novel surface-contact electrode array customized for the small intestine anatomy enabled simultaneous pacing and high-resolution response mapping. The spatial response of small intestine bioelectrical activity to pacing was mapped for the first time in vivo. Antegrade and circumferential pacing achieved spatial entrainment over 70% of the time and their induced pattern was held for 4-6 cycles postpacing at high energy (4 mA, 100 ms, at ∼2.7 s which corresponds to 1.1 × intrinsic frequency).

Stomach Geometry Reconstruction Using Serosal Transmitting Coils and Magnetic Source Localization.

OBJECTIVE: Bioelectric slow waves (SWs) are a key regulator of gastrointestinal motility, and disordered SW activity has been linked to motility disorders. There is currently a lack of practical options for the acquisition of the 3D stomach geometry during research studies when medical imaging is challenging. Accurately recording the geometry of the stomach and co-registering electrode and sensor positions would provide context for in-vivo studies and aid the development of non-invasive methods of gastric SW assessment. METHODS: A stomach geometry reconstruction method based on the localization of transmitting coils placed on the gastric serosa was developed. The positions and orientations of the coils, which represented boundary points and surface-normal vectors, were estimated using a magnetic source localization algorithm. Coil localization results were then used to generate surface models. The reconstruction method was evaluated against four 3D-printed anatomically realistic human stomach models and applied in a proof of concept in-vivo pig study. RESULTS: Over ten repeated reconstructions, average Hausdorff distance and average surface-normal vector error values were 4.7 ±0.2 mm and 18.7 ±0.7° for the whole stomach, and 3.6 ±0.2 mm and 14.6 ±0.6° for the corpus. Furthermore, mean intra-array localization error was 1.4 ±1.1 mm for the benchtop experiment and 1.7 ±1.6 mm in-vivo. CONCLUSION AND SIGNIFICANCE: Results demonstrated that the proposed reconstruction method is accurate and feasible. The stomach models generated by this method, when co-registered with electrode and sensor positions, could enable the investigation and validation of novel inverse analysis techniques.

Systematic review of small intestine pacing parameters for modulation of gut function.

BACKGROUND AND PURPOSE: The efficacy of conventional treatments for severe and chronic functional motility disorders remains limited. High-energy pacing is a promising alternative therapy for patients that fail conventional treatment. Pacing primarily regulates gut motility by modulating rhythmic bio-electrical events called slow waves. While the efficacy of this technique has been widely investigated on the stomach, its application in the small intestine is less developed. This systematic review was undertaken to summarize the status of small intestinal pacing and evaluate its efficacy in modulating bowel function through preclinical research studies. METHODS: The literature was searched using Scopus, PubMed, Ovid, Cochrane, CINAHL, and Google Scholar. Studies investigating electrophysiological, motility, and/or nutrient absorption responses to pacing were included. A critical review of all included studies was conducted comparing study outcomes against experimental protocols. RESULTS: The inclusion criteria were met by 34 publications. A range of pacing parameters including amplitude, pulse width, pacing direction, and its application to broad regional small intestinal segments were identified and assessed. Out of the 34 studies surveyed, 20/23 studies successfully achieved slow-wave entrainment, 9/11 studies enhanced nutrient absorption and 21/27 studies modulated motility with pacing. CONCLUSION: Small intestine pacing shows therapeutic potential in treating disorders such as short bowel syndrome and obesity. This systematic review proposes standardized protocols to maximize research outcomes and thereby translate to human studies for clinical validation. The use of novel techniques such as high-resolution electrical, manometric, and optical mapping in future studies will enable a mechanistic understanding of pacing.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

Non-invasive assessment of swallowing using flexible high-density electromyography arrays.

Swallowing is a vital function that serves to safely transport food and fluid to the stomach, while simultaneously protecting our airways. Evaluation of swallowing is important for the diagnosis and rehabilitation of individuals with dysphagia, a disorder of swallowing. Flexible high-density surface electromyography (HD sEMG) arrays were designed and fabricated to span the floor of mouth and neck muscles. These arrays were applied on 6 healthy participants over duplicate recording sessions. During each recording session, participants performed three different swallowing motor tasks. The HD sEMG signals were filtered and tasks extracted. For each task, the RMS amplitude was computed, visualized, and compared. Dynamic motor coordination was evident in the filtered signals traces, with different electrode locations showing unique temporal activations. The 2D topographical maps allowed the location of different RMS intensities to be visualized, revealing qualitatively similar patterns across participants and tasks. These motor task trends were also seen within RMS quantifications. The RMS metric across all participants identified significant differences between non-effortful 3 ml and effortful 3 ml swallow tasks ( p=0.006) and there was a minimal variation of 3.1±1.9 µV RMS for repeated recording sessions by each participant. The HD-sEMG array successfully recorded differences in muscle activations during swallowing and was able to discern between two different motor tasks. The arrays offers a spatially detailed non-invasive assessment of the neuromuscular performance of swallowing. Clinical Relevance- The utility of HD-sEMG arrays for evaluation of the muscles involved in swallowing could enable diagnosis and rehabilitation of individuals with dysphagia.

A generalized framework for pacing artifact removal using a Hampel filter.

Cardiac pacing is a clinical therapy widely used for treating irregular heart rhythms. Equivalent techniques for the treatment of gastric functional motility disorders hold great potential. Accurate analysis of pacing studies is often hindered by the stimulus artifacts which are superimposed on the recorded signals. This paper presents a semi-automated artifact detection method using a Hampel filter accompanied by 2 separate artifact reconstruction methods: (i) an auto-regressive model, and (ii) weighted mean to estimate the underlying signal. The developed framework was validated on synthetic and experimental signals containing large periodic pacing artifacts alongside evoked bioelectrical events. The performance of the proposed algorithms was quantified for gastric and cardiac pacing data collected in vivo. A lower mean RMS difference was achieved by the artifact segment reconstructed using the auto-regression ([Formula: see text]), method compared to the weighted mean ([Formula: see text]) method. Therefore, a more accurate artifact reconstruction was provided by the auto-regression approach. Clinical Relevance- The ability to efficiently and accurately isolate evoked bioelectrical events by eliminating large artifacts is a critical advancement for the analysis of paced recordings. The developed framework allows more efficient analysis of preclinical pacing data and thereby contributes to the advancement of pacing as a clinical therapy.

Anatomically Constrained Gastric Slow Wave Localization using Biomagnetic Data.

Detection of dysrhythmic gastric slow wave (SW) activity could have significant clinical utility because dysrhyth-mias have been linked to gastric motility disorders. The elec-trogastrogram (EGG) and magnetogastrogram (MGG) enable the non-invasive assessment of SW activity, but most analysis methods can only resolve frequency and velocity. Improved characterization of dysrhythmic propagation patterns from non-invasive measurements is important for the diagnosis of motility disorders and could allow early treatment stratification. In this study, we demonstrate the use of a penalized linear regression framework to localize SW events on the longitudinal stomach axis using simulated MGG data. Priors relating to spatial sparsity, the organization of wavefronts into complete circumferential rings, and the local distribution of depolar-ization and repolarization phases were used to constrain the inverse solution. This method was applied to MGG computed for a single wavefront case and a multiple wavefront case that were constructed from simulated 3 cycle-per-minute normal SW activity. Propagation patterns along the longitudinal stomach axis were identifiable from reconstructed SW activity for both cases. Localization error was 5.7 ± 0.1 mm and 7.7 ± 0.1 mm for each respective case within the distal stomach when the signal-to-noise ratio was 10 dB. Results indicate that penalized linear regression can successfully localize SW events provided the 3D geometry of the stomach and torso were acquired. Clinical Relevance- This method could help to improve the efficiency and accuracy of diagnosing gastric motility disorders from non-invasive measurements.

Gastric pacing response evaluated with simultaneous electrical and optical mapping.

Gastric pacing is an attractive therapeutic approach for correcting abnormal bioelectrical activity. While high-resolution (HR) electrical mapping techniques have largely contributed to the current understanding of the effect of pacing on the electrophysiological function, these mapping techniques are restricted to surface contact electrodes and the signal quality can be corrupted by pacing artifacts. Optical mapping of voltage sensitive dyes is an alternative approach used in cardiac research, and the signal quality is not affected by pacing artifacts. In this study, we simultaneously applied HR optical and electrical mapping techniques to evaluate the bioelectrical slow wave response to gastric pacing. The studies were conducted in vivo on porcine stomachs ( n=3) where the gastric electrical activity was entrained using high-energy pacing. The pacing response was optically tracked using voltage-sensitive fluorescent dyes and electrically tracked using surface contact electrodes positioned on adjacent regions. Slow waves were captured optically and electrically and were concordant in time and direction of propagation with comparable mean velocities ([Formula: see text]) and periods ([Formula: see text]). Importantly, the optical signals were free from pacing artifacts otherwise induced in electrical recordings highlighting an advantage of optical mapping. Clinical Relevance- Entrainment mapping of gastric pacing using optical techniques is a major advance for improving the preclinical understanding of the therapy. The findings can thereby inform the efficacy of gastric pacing in treating functional motility disorders.

The bioelectrical conduction system around the ileocecal junction defined through in vivo high-resolution mapping in rabbits.

Coordinated contractions across the small and large intestines via the ileocecal junction (ICJ) are critical to healthy gastrointestinal function and are in part governed by myoelectrical activity. In this study, the spatiotemporal characteristics of the bioelectrical conduction across the ICJ and its adjacent regions were quantified in anesthetized rabbits. High-resolution mapping was applied from the terminal ileum (TI) to the sacculus rotundus (SR), across the ICJ and into the beginning of the large intestine at the cecum ampulla coli (AC). Orally propagating slow wave patterns in the SR did not entrain the TI. However, aborally propagating patterns from the TI were able to entrain the SR. Bioelectrical activity was recorded within the ICJ and AC, revealing complex interactions of slow waves, spike bursts, and bioelectrical quiescence. This suggests the involvement of myogenic coordination when regulating motility between the small and large intestines. Mean slow wave frequency between regions did not vary significantly (13.74-17.16 cycles/min). Slow waves in the SR propagated with significantly faster speeds (18.51 ± 1.57 mm/s) compared with the TI (14.05 ± 2.53 mm/s, P = 0.0113) and AC (9.56 ± 1.56 mm/s, P = 0.0001). Significantly higher amplitudes were observed in both the TI (0.28 ± 0.13 mV, P = 0.0167) and SR (0.24 ± 0.08 mV, P = 0.0159) within the small intestine compared with the large intestine AC (0.03 ± 0.01 mV). We hypothesize that orally propagating slow waves facilitate a motor-brake pattern in the SR to limit outflow into the ICJ, similar to those previously observed in other gastrointestinal regions.NEW & NOTEWORTHY Competing slow wave pacemakers were observed in the terminal ileum and sacculus rotundus. Prevalent oral propagation in the sacculus rotundus toward the terminal ileum potentially acts as a brake mechanism limiting outflow. Slow waves and periods of quiescence at the ileocecal junction suggest that activation may depend on the coregulatory flow and distention pathways. Slow waves and spike bursts in the cecum impart a role in the coordination of motility.