Slow-wave coupling across a gastroduodenal anastomosis as a mechanism for postsurgical gastric dysfunction: evidence for a "gastrointestinal aberrant pathway".

Postsurgical gastric dysfunction is common, but the mechanisms are varied and poorly understood. The pylorus normally acts as an electrical barrier isolating gastric and intestinal slow waves. In this report, we present an aberrant electrical conduction pathway arising between the stomach and small intestine, following pyloric excision and surgical anastomosis, as a novel disease mechanism. A patient was referred with postsurgical gastroparesis following antrectomy, gastroduodenostomy, and vagotomy for peptic ulceration. Scintigraphy confirmed markedly abnormal 4-h gastric retention. Symptoms included nausea, vomiting, postprandial distress, and reflux. Intraoperative, high-resolution electrical mapping was performed across the anastomosis immediately before revision gastrectomy, and the resected anastomosis underwent immunohistochemistry for interstitial cells of Cajal. Mapping revealed continuous, stable abnormal retrograde slow-wave propagation through the anastomosis, with slow conduction occurring at the scar (4.0 ± 0.1 cycles/min; 2.5 ± 0.6 mm/s; 0.26 ± 0.15 mV). Stable abnormal retrograde propagation continued into the gastric corpus with tachygastria (3.9 ± 0.2 cycles/min; 1.6 ± 0.5 mm/s; 0.19 ± 0.12 mV). Histology confirmed ingrowth of atypical ICC through the scar, defining an aberrant pathway enabling transanastomotic electrical conduction. In conclusion, a "gastrointestinal aberrant pathway" is presented as a novel proposed cause of postsurgical gastric dysfunction. The importance of aberrant anastomotic conduction in acute and long-term surgical recovery warrants further investigation.NEW & NOTEWORTHY High-resolution gastric electrical mapping was performed during revisional surgery in a patient with severe gastric dysfunction following antrectomy and gastroduodenostomy. The results revealed continuous propagation of slow waves from the duodenum to the stomach, through the old anastomotic scar, and resulting in retrograde-propagating tachygastria. Histology showed atypical interstitial cells of Cajal growth through the anastomotic scar. Based on these results, we propose a "gastrointestinal aberrant pathway" as a mechanism for postsurgical gastric dysfunction.

Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.

High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm2) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 ± 0.1 mV to 2.5 ± 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration.

Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting.

BACKGROUND & AIMS: Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, therefore the diseases may share pathophysiologic features. We investigated this hypothesis by quantifying densities of interstitial cells of Cajal (ICCs) and mapping slow-wave abnormalities in patients with CUNV vs controls. METHODS: Clinical data and gastric biopsy specimens were collected from 9 consecutive patients with at least 6 months of continuous symptoms of CUNV but normal gastric emptying who were treated at the University of Mississippi Medical Center, and from 9 controls (individuals free of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural analyses were performed on tissue samples. Slow-wave propagation profiles were defined by high-resolution electrical mapping (256 electrodes; 36 cm(2)). Results from patients with CUNV were compared with those of controls as well as patients with gastroparesis who were studied previously by identical methods. RESULTS: Patients with CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field, respectively; P < .05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1 of 9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wavefront collisions, conduction blocks, and re-entry), operating across bradygastric, normal (range, 2.4-3.7 cycles/min), and tachygastric frequencies; dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal vs 7.6 mm/s circumferential; P < .01). ICCs were less depleted in patients with CUNV than in those with gastroparesis (mean, 3.5 vs 2.3 bodies/field, respectively; P < .05), but slow-wave dysrhythmias were similar between groups. CONCLUSIONS: This study defined cellular and bioelectrical abnormalities in patients with CUNV, including the identification of slow-wave re-entry. Pathophysiologic features of CUNV were observed to be similar to those of gastroparesis, indicating that they could be spectra of the same disorder. These findings offer new insights into the pathogenesis of CUNV and may help to inform future treatments.

Acute Slow Wave Responses to High-Frequency Gastric Electrical Stimulation in Patients With Gastroparesis Defined by High-Resolution Mapping.

BACKGROUND AND AIMS: High-frequency gastric electrical stimulation (GES) has emerged as a therapy for gastroparesis, but the mechanism(s) of action remain unclear. There is a need to refine stimulation protocols for clinical benefit, but a lack of accurate techniques for assessing mechanisms in clinical trials, such as slow wave modulation, has hindered progress. We thereby aimed to assess acute slow wave responses to GES in gastroparesis patients using high-resolution (HR) (multi-electrode) mapping, across a range of stimulation doses achievable by the Enterra stimulation device (Medtronic Inc., MN, USA). MATERIALS AND METHODS: Patients with medically refractory gastroparesis (n = 8) undergoing device implantation underwent intraoperative HR mapping (256 electrodes). Baseline recordings were followed by four protocols of increasing stimulation intensity, with washout periods. Slow wave patterns, frequency, velocity, amplitude, and dysrhythmia rates were quantified by investigators blinded to stimulation settings. RESULTS: There was no difference in slow wave pattern, frequency, velocity, or amplitude between baseline, washout, and stimulation periods (all p > 0.5). Dysrhythmias included ectopic pacemakers, conduction blocks, retrograde propagation, and colliding wavefronts, and dysrhythmia rates were unchanged with stimulation off vs. on (31% vs. 36% duration dysrhythmic; p > 0.5). Symptom scores and gastric emptying were improved at 5.8 month follow-up (p < 0.05). CONCLUSIONS: High-frequency GES protocols achievable from a current commercial device did not acutely modulate slow wave activity or dysrhythmias. This study advances clinical methods for identifying and assessing therapeutic GES parameters, and can be applied in future studies on higher-energy protocols and devices.

The bioelectrical basis and validity of gastrointestinal extracellular slow wave recordings.

Gastrointestinal extracellular recordings have been a core technique in motility research for a century. However, the bioelectrical basis of extracellular data has recently been challenged by claims that these techniques preferentially assay movement artifacts, cannot reproduce the underlying slow wave kinetics, and misrepresent the true slow wave frequency. These claims motivated this joint experimental-theoretical study, which aimed to define the sources and validity of extracellular potentials. In vivo extracellular recordings and video capture were performed in the porcine jejunum, before and after intra-arterial nifedipine administration. Gastric extracellular recordings were recorded simultaneously using conventional serosal contact and suction electrodes, and biphasic and monophasic extracellular potentials were simulated in a biophysical model. Contractions were abolished by nifedipine, but extracellular slow waves persisted, with unchanged amplitude, downstroke rate, velocity, and downstroke width (P>0.10 for all), at reduced frequency (24% lower; P=0.03). Simultaneous suction and conventional serosal extracellular recordings were identical in phase (frequency and activation-recovery interval), but varied in morphology (monophasic vs. biphasic; downstroke rate and amplitude: P<0.0001). Simulations demonstrated the field contribution of current flow to extracellular potential and quantified the effects of localised depolarisation due to suction pressure on extracellular potential morphology. In sum, these results demonstrate that gastrointestinal extracellular slow wave recordings cannot be explained by motion artifacts, and are of a bioelectrical origin that is highly consistent with the underlying biophysics of slow wave propagation. Motion suppression is shown to be unnecessary as a routine control in in vivo extracellular studies, supporting the validity of the extant gastrointestinal extracellular literature.

Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) generate slow waves. Disrupted ICC networks and gastric dysrhythmias are each associated with gastroparesis. However, there are no data on the initiation and propagation of slow waves in gastroparesis because research tools have lacked spatial resolution. We applied high-resolution electrical mapping to quantify and classify gastroparesis slow-wave abnormalities in spatiotemporal detail. METHODS: Serosal high-resolution mapping was performed using flexible arrays (256 electrodes; 36 cm(2)) at stimulator implantation in 12 patients with diabetic or idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and amplitude field mapping, and propagation animation. ICC numbers were determined from gastric biopsy specimens. RESULTS: Mean ICC counts were reduced in patients with gastroparesis (2.3 vs 5.4 bodies/field; P < .001). Slow-wave abnormalities were detected by high-resolution mapping in 11 of 12 patients. Several new patterns were observed and classified as abnormal initiation (10/12; stable ectopic pacemakers or diffuse focal events; median, 3.3 cycles/min; range, 2.1-5.7 cycles/min) or abnormal conduction (7/10; reduced velocities or conduction blocks; median, 2.9 cycles/min; range, 2.1-3.6 cycles/min). Circumferential conduction emerged during aberrant initiation or incomplete block and was associated with velocity elevation (7.3 vs 2.9 mm s(-1); P = .002) and increased amplitudes beyond a low base value (415 vs 170 µV; P = .002). CONCLUSIONS: High-resolution mapping revealed new categories of abnormal human slow-wave activity. Abnormalities of slow-wave initiation and conduction occur in gastroparesis, often at normal frequency, which could be missed by tests that lack spatial resolution. Irregular initiation, aberrant conduction, and low amplitude activity could contribute to the pathogenesis of gastroparesis.

The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail.

BACKGROUND: Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail. RESULTS: GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user-friendly graphical user interface. GEMS is implemented using MATLAB®, which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (http://sites.google.com/site/gimappingsuite). CONCLUSIONS: This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping.

High-Resolution Spatiotemporal Quantification of Intestinal Motility With Free-Form Deformation.

OBJECTIVE: To develop a method to quantify strain fields from in vivo intestinal motility recordings that mitigate accumulation of tracking error. METHODS: The deforming geometry of the intestine in video sequences was modeled by a biquadratic B-spline mesh. Green-Lagrange strain fields were computed to quantify the surface deformations. A nonlinear optimization scheme was applied to mitigate the accumulation of tracking error associated with image registration. RESULTS: The optimization scheme maintained the RMS strain error under 1% and reduced the rate of strain error by 97% during synthetic tests. The algorithm was applied to map 64 segmental, 12 longitudinal, and 23 propagating circular contractions in the jejunum. Coordinated activity of the two muscle layers could be identified and the strain fields were able to map and quantify the anisotropic contractions of the intestine. Frequency and velocity were also quantified, from which two types of propagating circular contractions were identified: (i) [Formula: see text] strain contractions that originated spontaneously and propagated at [Formula: see text] mm/s in two pigs, and (ii) cyclic propagating contractions of [Formula: see text] strain occurred at [Formula: see text] cpm and propagated at [Formula: see text] mm/s in a rabbit. CONCLUSION: The algorithm simultaneously mapped the circular, longitudinal activity of the intestine with high spatial resolution and quantified anisotropic contractions and relaxations. SIGNIFICANCE: The proposed algorithm can now be used to define the interactions of muscle layers during motility patterns. It can be integrated with high-resolution bioelectrical recordings to investigate the regulatory mechanisms of motility.

The influence of interstitial cells of Cajal loss and aging on slow wave conduction velocity in the human stomach.

Loss of interstitial cells of Cajal (ICC) has been associated with gastric dysfunction and is also observed during normal aging at ~13% reduction per decade. The impact of ICC loss on gastric slow wave conduction velocity is currently undefined. This study correlated human gastric slow wave velocity with ICC loss and aging. High-resolution gastric slow wave mapping data were screened from a database of 42 patients with severe gastric dysfunction (n = 20) and controls (n = 22). Correlations were performed between corpus slow wave conduction parameters (frequency, velocity, and amplitude) and corpus ICC counts in patients, and with age in controls. Physiological parameters were further integrated into computational models of gastric mixing. Patients: ICC count demonstrated a negative correlation with slow wave velocity in the corpus (i.e., higher velocities with reduced ICC; r2  = .55; p = .03). ICC count did not correlate with extracellular slow wave amplitude (p = .12) or frequency (p = .84). Aging: Age was positively correlated with slow wave velocity in the corpus (range: 25-74 years; r2  = .32; p = .02). Age did not correlate with extracellular slow wave amplitude (p = .40) or frequency (p = .34). Computational simulations demonstrated that the gastric emptying rate would increase at higher slow wave velocities. ICC loss and aging are associated with a higher slow wave velocity. The reason for these relationships is unexplained and merit further investigation. Increased slow wave velocity may modulate gastric emptying higher, although in gastroparesis other pathological factors must dominate to prevent emptying.

High-Resolution Mapping of Intestinal Spike Bursts and Motility.

Gastrointestinal (GI) motility and functional disorders affect up to 25% of the American population. Electrophysiological studies had shown a link between these functional motility disorders and abnormalities in GI bioelectrical activity. However, the dynamics between GI electrical activity (slow waves and spike bursts) and motility are not well understood. This study presents a framework to simultaneously record and quantify GI spike bursts and motility in vivo, in high-resolution. The dynamics between spike burst events and motility observed in 4 pig studies were investigated. A clear connection between spike burst patches and localized contractions was observed. The dataset consisted of 685 spike burst events in 191 patches. Contractions were associated with 81 patches. Spike burst patches associated with contractions had significantly higher amplitude, duration, and size compared to the ones that did not show an association. The amplitude, duration, and size of spike burst patches were positively correlated with the contraction strength. The spike burst patch energy displayed the highest correlation (r = 0.74). The contraction strength had a linear trend with spike burst patch energy. However, it could only account for 52% of the variance in contraction strength.

Design and Application of an Inflatable Cuff to Aid High-Resolution Intestinal Slow Wave Recordings.

Intestinal motility is coordinated by myogenic, neuronal and hormonal factors. Myogenic control of motility via bioelectric slow waves (SW) has been investigated using low-resolution and high-resolution (HR) electrical mapping techniques. Due to the highly conformable and irregular surface of the gut, suboptimal coverage of HR recordings may occur. In this study we designed and developed an inflatable cuff as a platform to apply even pressure across the intestinal surface to achieve consistent and reliable recordings. The inflatable cuff and a HR electrode array were applied in vivo to demonstrate the reliability of SW signal acquisition over a range of inflatable pressures (0 - 5 mm Hg). The frequency, amplitude, percentage of viable signals and signal to noise ratio metrics of the SW signals were computed and compared. Overall, with an increase in inflatable pressure from 0 to 5 mm Hg, the frequency did not change, but the amplitude of the SWs decreased from 0.10 to 0.07 mV. The noise levels were consistent across the range of inflatable pressure levels and the percentage of viable SW recordings improved significantly from 57% to 74% after application of 1 mm Hg of pressure. The inflatable and conformable cuff presented in this study provides a reliable platform for HR mapping of bioelectrical events in the intestines and other conformable organs.Clinical Relevance- This framework improves the quality and reliability of bioelectrical high-resolution recordings obtained from the small intestine. In the future, these recordings will improve our understanding of the pathophysiological mechanisms governing intestinal motility disorders and may provide clinicians with new strategies for diagnosis and treatment.

A Spatially-dense Microfabricated Photolithographic Electrode Array for Gastrointestinal Slow Wave Recordings.

Gastrointestinal slow wave activity is, in part, responsible for governing gut motility. Dysrhythmic slow wave activity has been associated with a number of functional motility disorders, but the mechanisms involved are poorly understood. There exist a number of transgenic small animal models with functional motility disorders. However, current slow wave mapping methods are targeted towards humans and large animals and are not readily translatable. To overcome these shortcomings, a novel electrode array was developed using photolithography. The developed photolithographic electrode array (PEA) was experimentally validated in vivo against a standard flexible printed circuit (FPC) array for comparison. Mean amplitudes of 0.13 ± 0.06 mV and 0.88 ± 0.05 mV were reported by the PEA and the FPC array, respectively. Mean signal to noise ratios (SNR) of 13.4 ± 6.4 dB and 8.3 ± 5.1 dB were achieved for the PEA and the FPC array, respectively. Our findings showed that the PEA acquired slow wave signals with higher amplitude and SNR. In this study, we showed that microfabrication techniques could be successfully implemented with optimized resolution for the investigation of normal and abnormal slow wave activity in smaller animals, which will enable a better understanding of the pathophysiological mechanisms and aid in the diagnosis and treatment of gastrointestinal motility disorders.Clinical Relevance - The ability to characterize the slow wave activity in transgenic animals with functional motility disorders would be a critical advance for the diagnosis and treatment of these disorders. Microfabrication techniques enable miniaturization of high-resolution electrode arrays suitable for mapping electrical activity in normal and transgenic small laboratory animals such as rats and mice.

Design of Pressure Sensor Arrays to Assess Electrode Contact Pressure During In Vivo Recordings in the Gut.

The gastrointestinal (GI) tract is in part controlled by slow wave electrical activity. Recordings of slow waves with high-resolution (HR) electrode arrays are used to characterize normal and abnormal conduction pathways. Improving the quality of these electrical recordings is important for developing a better understanding of abnormal activity. Contact pressure is one factor that can affect the quality of electrical recordings. We compared the performance of two pressure sensing devices for measuring HR electrode array contact pressure. A Velostat-based sensor array was custom designed and built in a 4 × 2 conguration (area: 30 mm2 per sensor) to be integrated into electrical recordings. Commercially available FlexiForce A201 sensors were used to compare to the Velostat-based sensors. Benchtop testing of these sensors was performed; the error of the Velostat-based sensors (14-31%) was better than that of the FlexiForce sensors (20-49%) within a range of 2666-6666 Pa. The Velostat-based sensors were also more repeatable than the FlexiForce sensors over the same pressure range. Simultaneous pressure and slow wave recordings were performed in vivo on a rabbit small intestine. The Velostat-based sensors were able to resolve spatiotemporal changes in contact pressure in the range of 0-10 000 Pa.

Effects of Electrode Diameter and Contact Material on Signal Morphology of Gastric Bioelectrical Slow Wave Recordings.

Gastric motility is governed in part by bioelectrical 'slow waves', and high-resolution electrical mapping has emerged as a clinical research tool with diagnostic potential. In this study, we aimed to determine the effects of electrode diameter and contact material on in vivo extracellular slow wave recordings to inform gastric mapping device design. Custom flexible-printed-circuit electrode arrays were designed with four electrode diameters (0.3, 1.8, 3.3, 4.8 mm; 4 × 8 array) and fabricated in four contact materials (gold, silver, copper, silver-chloride). The electrode arrays were placed on the gastric serosa in vivo in pigs and unipolar slow wave signals were simultaneously recorded from each electrode. Propagation, signal morphology, and noise were quantified to determine which electrodes produced signals with the highest signal-to-noise ratio (SNR) and gradient, which is a preferred metric for detection and analytical algorithms. Electrodes of diameters 0.3 and 1.8 mm recorded significantly higher signal gradients than 3.3 and 4.8 mm (p < 0.05). Silver-chloride electrodes recorded a significantly higher gradient than all other materials (p < 0.05), with no significant differences between gold, silver, and copper electrodes. Electrodes of diameters 1.8 and 3.3 mm recorded significantly higher SNR than 0.3 mm (p < 0.05). Electrodes with a diameter of 1.8 mm provided an optimal combination to maximize the signal gradient and SNR, and silver-chloride electrodes yielded the highest signal gradient. These results can now inform gastric mapping device design, particularly minimally-invasive devices where electrode size is critical.

A V-Net Based Deep Learning Model for Segmentation and Classification of Histological Images of Gastric Ablation.

Gastric motility disorders are associated with bioelectrical abnormalities in the stomach. Recently, gastric ablation has emerged as a potential therapy to correct gastric dysrhythmias. However, the tissue-level effects of gastric ablation have not yet been evaluated. In this study, radiofrequency ablation was performed in vivo in pigs (n=7) at temperature-control mode (55-80°C, 5-10 s per point). The tissue was excised from the ablation site and routine H&E staining protocol was performed. In order to assess tissue damage, we developed an automated technique using a fully convolutional neural network to segment healthy tissue and ablated lesion sites within the muscle and mucosa layers of the stomach. The tissue segmentation achieved an overall Dice score accuracy of 96.18 ± 1.0 %, and Jacquard score of 92.77 ± 1.9 %, after 5-fold cross validation. The ablation lesion was detected with an overall Dice score of 94.16 ± 0.2 %. This method can be used in combination with high-resolution electrical mapping to define the optimal ablation dose for gastric ablation.Clinical Relevance-This work presents an automated method to quantify the ablation lesion in the stomach, which can be applied to determine optimal energy doses for gastric ablation, to enable clinical translation of this promising emerging therapy.

Computational Reconstruction of 3D Stomach Geometry using Magnetic Field Source Localization.

In this study, we investigated the feasibility of computationally reconstructing the 3D geometry of the stomach by performing source localization of the magnetic field (MF) induced from the stomach surface. Anatomically realistic stomach and torso models of a human participant, reconstructed from the CT images, were used in the computations. First, 128 coils with a radius of 5 mm were positioned on different locations on the stomach model. Next, MF at the sensor positions were computed using Bio-Savart law for the currents of 10 and 100 mA. Then, three noise levels were defined using the biomagnetic data recorded from the same participant and two additional sets of generated white-noise resulting in mean signal to noise ratios (SNR) of 20 and 10 dB. Finally, for each combination of the current and noise level, the magnetic dipole (MDP) approximation was performed to estimate coil positions. The performance of the source localization was assessed by computing the goodness of fit (GOF) values and the distance between the coil and the estimated MDP positions. We obtained GOF values over 98% for all coils and a mean localization error of 0.69±0.08 mm was achieved when 100 mA current was used to induce MF and only biomagnetic data was added. When additional white-noise was added, the GOF values decreased to 95% and the mean localization error increased to around 4 mm. A current of 10 mA was enough to localize the coil positions with a mean error around 8 mm even for the highest noise level we tested but for the few coils furthest from the body surface, the error was around 10 cm. The results indicate that source localization using the MDP approximation can successfully extract spatial information of the stomach.Clinical relevance-Extracting the spatial information of the stomach during the recording of the slow wave activity provides new insights in assessing gastric recordings and relating to disorders.

Trace Mapping: A New Visualization Technique for Analyzing Gastrointestinal High-Resolution Electrical Mapping Data.

Visualization techniques are an important tool for understanding high-resolution mapping data in gastric electrophysiology. Isochronal maps and animations provide excellent depictions of spatial propagation patterns, but fail to capture temporal features of electrical activity. In this work, 'trace mapping' was developed and validated as a method for visualizing high-resolution mapping data. A combination of dots and lines represent events and temporal groups, respectively, creating patterns that can be quickly and efficiently interpreted. This work outlines trace mapping methods and introduces a shape-based pattern recognition method for efficient interpretation of trace maps. These methods provide a new perspective for understanding and evaluating gastric electrophysiology.Clinical Relevance-This work provides new visualization methods that can help clinicians interpret and diagnose gastric electrical abnormalities in patients with functional gastrointestinal disorders.

Transmural Temperature Monitoring to Quantify Thermal Conduction And Lesion Formation During Gastric Ablation, an Emerging Therapy for Gastric Dysrhythmias.

Gastric ablation is emerging as a potential therapy for electrical dysrhythmias associated with gastric disorders. Thermal conduction properties of gastric tissue during ablation have not yet been defined, but are necessary for optimizing the technique and translating ablation to clinical therapy. We developed custom needle-based transmural temperature probes to quantify the temperature of gastric tissue during ablation. These probes were applied in vivo in pigs (n=5), during gastric ablation (70 °C, 10 s duration), at distances of 2.5 - 20 mm from the ablation catheter tip. Thermal response of the tissue was non-linear; the maximum temperature increase from baseline (33.3 ± 1.0 °C) was observed at the closest temperature probe to the catheter tip (2.5 mm, 14.9 °C), and temperature change decreased with distance from the catheter tip. Probes positioned between 5 -20 mm from the catheter tip recorded temperature increases of less than 5.6 °C. This study provides methods for monitoring temperature during in vivo ablation, and demonstrates that functional temperature increases from ablation were restricted to within approximately 5 mm of the catheter. These methods can now be applied to optimize effective ablation parameters, and to inform models of gastric ablation.

Detection of Monophasic Slow-wave Activation Phase Using Wavelet Decomposition.

Gastric bio-electric slow-waves are in part responsible for generating motility. Extracellular recordings of the slow-wave activation phase have yielded significant physiological insight about its spatio-temporal characteristics. With the growth of multi-electrode data and long recording periods, there is a need for automated methods to detect the activation phase in a reliable and accurate manner. In this study, the Variable Threshold Wavelet (VTW) algorithm was developed, featuring wavelet decomposition, to compute the derivative to detect the slow-wave activation phase of monophasic signals. The performance of the VTW algorithm was compared against an existing Falling-Edge, Variable Threshold (FEVT) algorithm. Varying levels of synthetic noise representing ventilator and high-frequency noise were added to in vivo slow-wave recordings. Sensitivity, positive-predictive value, area under the curve (Aroc) metric and percentage improvement metric (PIM) of activation phase identification accuracy were calculated. Compared to the existing FEVT algorithm, the VTW algorithm achieved similar performance in identifying the activation phase of slow-waves with various levels of ventilator noise. In the presence of high-frequency noise, the VTW algorithm improved the Aroc of the existing FEVT algorithm by 11.1%. The VTW algorithm can now be applied to analyze normal and abnormal slow-wave recordings.

Dynamic slow-wave interactions in the rabbit small intestine defined using high-resolution mapping.

BACKGROUND: The motility in the small intestine is governed in part by myogenic bio-electrical events, known as slow waves. High-resolution multi-electrode mapping has improved our understanding of slow-wave propagation in the small intestine but has been applied in a limited number of in vivo animal studies. This study applied high-resolution mapping to investigate slow waves in the rabbit small intestine. METHODS: A high-resolution flexible printed circuit board array (256 electrodes; 4 mm spacing) was applied in vivo to the rabbit intestine. Extracellular slow-wave activity was acquired sequentially along the length of the intestine. KEY RESULTS AND CONCLUSIONS: The majority of the slow waves propagated in the antegrade direction (56%) while retrograde patterns were primarily observed in the distal intestine (29%). Colliding slow-wave events were observed across the length of the small intestine (15%). The interaction of competing pacemakers was mapped in spatiotemporal detail. The frequency and velocity of the slow waves were highest in the duodenum compared to ileum (20.0 ± 1.2 cpm vs 10.5 ± 0.9 cpm, P < 0.001; 14.4 ± 3.4 mm/s vs 12.3 ± 3.4 mm/s; P < 0.05). INFERENCES: In summary, extracellular serosal slow-wave activity was quantified spatiotemporally along the length of the rabbit intestine. In particular, the study provides evidence toward the presence and interaction of slow-wave pacemakers acting along the small intestine and how they may contribute to the slow-wave frequency gradient along the length of the intestine.