Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

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.

Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 ± 0.2 mm/s, P>0.05). However, SPE had higher loss of tissue lead contact quality than CPE (42 ± 16 vs 13 ± 10% over 20 min). CONCLUSION: Pacing with SPE induced a slow-wave pacemaker site without tissue damage. SIGNIFICANCE: SPE offered an atraumatic pacing electrode with a significant reduction of power consumption and placement time compared to impaled electrodes.

Reconstruction of stomach geometry using magnetic source localization.

Routine diagnosis of gastric motility disorders represents a significant problem to current clinical practice. The non-invasive electrogastrogram (EGG) and magnetogastrogram (MGG) enable the assessment of gastric slow wave (SW) dysrhythmias that are associated with motility disorders. However, both modalities lack standardized methods for reliably detecting patterns of SW activity. Subject-specific anatomical information relating to the geometry of the stomach and its position within the torso have the potential to aid the development of relations between SWs and far-fields. In this study, we demonstrated the feasibility of using magnetic source localization to reconstruct the geometry of an anatomically realistic 3D stomach model. The magnetic fields produced by a small (6.35 × 6.35 mm) N35 neodymium magnet sequentially positioned at 64 positions were recorded by an array of 27 magnetometers. Finally, the magnetic dipole approximation and a particle swarm optimizer were used to estimate the position and orientation of the permanent magnet. Median position and orientation errors of 3.8 mm and 7.3° were achieved. The estimated positions were used to construct a surface mesh, and the Hausdorff Distance and Average Hausdorff Distance dissimilarity metrics for the reconstructed and ground-truth models were 11.6 mm and 2.4 mm, respectively. The results indicate that source localization using the magnetic dipole model can successfully reconstruct the geometry of the stomach.

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.

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.

A Novel Gastric Pacing Device to Modulate Slow Waves and Assessment by High-Resolution Mapping.

OBJECTIVE: The use of electrical pacing in the gastrointestinal field continues to advance clinical and basic science; however, the efficacy and effectiveness of gastric stimulation and pacing remains limited. In the stomach, rhythmic bioelectrical events, known as slow waves, coordinate the muscular contractions that aid digestion. A range of slow wave abnormalities have been shown to be associated with functional motility disorders, such as gastroparesis, chronic unexplained nausea and vomiting, and functional dyspepsia. Pacing is an attractive therapeutic approach to revert slow wave abnormalities. However, there are currently no clinical gastric pacing devices in active use. In this study, a novel battery-powered pacing device was developed, implementing wireless control and tissue electrical parameter monitoring. METHODS: The pacing device was applied in five pigs in vivo along with high-resolution (HR) mapping to validate the device and to elucidate the pacing response of slow waves. The pacing leads were placed in the middle of the HR array to determine any changes to the propagation pattern. The pacing period range was 14-30 s. RESULTS: In all studies, the novel pacing device initiated slow wave activation from a location near the pacing leads at the specified period. Slow wave propagation speed increased after pacing (from 6.4 ± 2.0 to 8.1 ± 3.2 mm/s; P < 0.001), commensurate with induction of paced anisotropic propagation. CONCLUSION: This study introduces a novel gastric pacing system suitable for clinical trials, achieving reliable induction of slow wave pacing at specific location and periods. The device is now available to be trialed as a therapeutic application for motility disorders and obesity.

Suppression of ventilation artifacts for gastrointestinal slow wave recordings.

Gastrointestinal extracellular slow wave recordings are providing critical information about normal motility and pathophysiology of the gut. Processing the signals is an important adjunct to acquire clinically and physiologically meaningful analysis. In stomach and intestine in vivo slow wave recordings, ventilation (or respiratory) artifacts can be prominent, which hinders identification and analysis of slow wave profiles. Here, we introduce an algorithm to suppress these artifacts without distorting the slow wave morphology. The algorithm generates a cycle averaged ventilation signal by shifting the raw signal by its ventilation period. The cycle averaged ventilation signal is then subtracted from the slow wave recording. The algorithm was validated using signal to noise ratio (SNR) and Pearson correlation coefficient (PCC) on synthetic signals and SNR with experimental recordings. With synthetic data, SNR and PCC, improved by 7.29±1.14 dB and 0.23±0.15.With experimental data SNR improved by 2.66±0.60 dB. This method improves the slow wave signal content revealing a more accurate estimate of the slow wave morphology. The application of this method will lead to improved analysis of slow wave recordings to understand gut function.

Design and application of a novel gastric pacemaker.

Omnipresent bioelectrical events known as slow waves are responsible for coordinating motility in the gastrointestinal tract. Functional motility diseases, such as gastroparesis, are associated with slow wave dysrhythmias. Electrical stimulation is a potential therapy to correct abnormal slow wave patterns. We present the design and application of a new gastric pacemaker. Real-time changes to the stimulation parameters such as period, amplitude and pulse width were applied using a graphical user interface, which communicated with the microcontroller to deliver the stimulus. The new pacemaker allows the voltage, delivered current and resistance between pacing electrodes to be continuously monitored. The pacing device was applied experimentally and was able to modulate and entrain gastric slow wave activity. After the onset of pacing, the direction of slow wave propagation was altered. Furthermore, the mean velocity and amplitude of slow wave activity increased from 4.7±1.5 to 5.4±1.3 mm/s, and from 1.1±1.1 to 1.7±0.9 mV, respectively. A simplified bidomain electrical model was used to simulate the recorded stimulus artifact. The model illustrated a new approach to evaluate if the stimulus has been delivered to the gastric tissue. The new pacing device and model will be used to investigate the mechanisms that allow pacing to entrain slow wave activity.