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.

Three-Dimensional Fractal Analysis of the Interstitial Cells of Cajal Networks of Gastrointestinal Tissue Specimens.

Introduction: Several functional gastrointestinal disorders (FGIDs) have been associated with the degradation or remodeling of the network of interstitial cells of Cajal (ICC). Introducing fractal analysis to the field of gastroenterology as a promising data analytics approach to extract key structural characteristics that may provide insightful features for machine learning applications in disease diagnostics. Fractal geometry has advantages over several physically based parameters (or classical metrics) for analysis of intricate and complex microstructures that could be applied to ICC networks. Methods: In this study, three fractal structural parameters: Fractal Dimension, Lacunarity, and Succolarity were employed to characterize scale-invariant complexity, heterogeneity, and anisotropy; respectively of three types of gastric ICC network structures from a flat-mount transgenic mouse stomach. Results: The Fractal Dimension of ICC in the longitudinal muscle layer was found to be significantly lower than ICC in the myenteric plexus and circumferential muscle in the proximal, and distal antrum, respectively (both p < 0.0001). Conversely, the Lacunarity parameters for ICC-LM and ICC-CM were found to be significantly higher than ICC-MP in the proximal and in the distal antrum, respectively (both p < 0.0001). The Succolarity measures of ICC-LM network in the aboral direction were found to be consistently higher in the proximal than in the distal antrum (p < 0.05). Conclusions: The fractal parameters presented here could go beyond the limitation of classical metrics to provide better understanding of the structural-functional relationship between ICC networks and the conduction of gastric bioelectrical slow waves.

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.

Biotrapping Ureolytic Bacteria on Sand to Improve the Efficiency of Biocementation.

Microbially induced calcium carbonate precipitation (MICP) has emerged as a novel technology with the potential to produce building materials through lower-temperature processes. The formation of calcium carbonate bridges in MICP allows the biocementation of aggregate particles to produce biobricks. Current approaches require several pulses of microbes and mineralization media to increase the quantity of calcium carbonate minerals and improve the strength of the material, thus leading to a reduction in sustainability. One potential technique to improve the efficiency of strength development involves trapping the bacteria on the aggregate surfaces using silane coupling agents such as positively charged 3-aminopropyl-methyl-diethoxysilane (APMDES). This treatment traps bacteria on sand through electrostatic interactions that attract negatively charged walls of bacteria to positively charged amine groups. The APMDES treatment promoted an abundant and immediate association of bacteria with sand, increasing the spatial density of ureolytic microbes on sand and promoting efficient initial calcium carbonate precipitation. Though microbial viability was compromised by treatment, urea hydrolysis was minimally affected. Strength was gained much more rapidly for the APMDES-treated sand than for the untreated sand. Three injections of bacteria and biomineralization media using APMDES-treated sand led to the same strength gain as seven injections using untreated sand. The higher strength with APMDES treatment was not explained by increased calcium carbonate accrual in the structure and may be influenced by additional factors such as differences in the microstructure of calcium carbonate bridges between sand particles. Overall, incorporating pretreatment methods, such as amine silane coupling agents, opens a new avenue in biomineralization research by producing materials with an improved efficiency and sustainability.

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.

Neural regulation of slow waves and phasic contractions in the distal stomach: a mathematical model.

Objective.Neural regulation of gastric motility occurs partly through the regulation of gastric bioelectrical slow waves (SWs) and phasic contractions. The interaction of the tissues and organs involved in this regulatory process is complex. We sought to infer the relative importance of cellular mechanisms in inhibitory neural regulation of the stomach by enteric neurons and the interaction of inhibitory and excitatory electrical field stimulation.Approach.A novel mathematical model of gastric motility regulation by enteric neurons was developed and scenarios were simulated to determine the mechanisms through which enteric neural influence is exerted. This model was coupled to revised and extended electrophysiological models of gastric SWs and smooth muscle cells (SMCs).Main results.The mathematical model predicted that regulation of contractile apparatus sensitivity to intracellular calcium in the SMC was the major inhibition mechanism of active tension development, and that the effect on SW amplitude depended on the inhibition of non-specific cation currents more than the inhibition of calcium-activated chloride current (kiNSCC= 0.77 vs kiAno1= 0.33). The model predicted that the interaction between inhibitory and excitatory neural regulation, when applied with simultaneous and equal intensity, resulted in an inhibition of contraction amplitude almost equivalent to that of inhibitory stimulation (79% vs 77% decrease), while the effect on frequency was overall excitatory, though less than excitatory stimulation alone (66% vs 47% increase).Significance.The mathematical model predicts the effects of inhibitory and excitatory enteric neural stimulation on gastric motility function, as well as the effects when inhibitory and excitatory enteric neural stimulation interact. Incorporation of the model into organ-level simulations will provide insights regarding pathological mechanisms that underpin gastric functional disorders, and allow forin silicotesting of the effects of clinical neuromodulation protocols for the treatment of these disorders.

Cervical Vagus Nerve Stimulation Disrupts Gastric Slow Wave Activity in Rats.

Cervical vagus nerve stimulation (cVNS) is a promising neuromodulation therapy for treating symptoms of disease in peripheral organs. The rat is a common animal model for studying and trialing new applications of cVNS therapy, but the stomach and its activity in rats is less well characterized than other animals, such as pigs. We sought to investigate the effects of acute, in vivo cVNS on gastric bioelectrical activity as an intermediate step to computational modeling of the effects of cVNS on gastric smooth muscle electromechanical coupling. Here we show a method of detecting bioelectrical gastric slow wave events using a non-linear energy operator. The marked events are compared to the underlying bioelectrical slow wave activity.The mean propagation velocity before stimulation was 0.79 ± 0.31 mm s-1, and the mean interval was 17.4 ± 1.4 s. During cVNS, there was a significant increase in velocity (1.02 ± 0.69 mm s-1; p < 0.001), and decrease in interval (15.4 ± 2.9 s; p = 0.0196). At stimulation onset, premature slow waves were induced at an ectopic pacemaker location and waves originating at the ectopic and initial pacemaker sites continued to collide following the cessation of cVNS.This work forms the basis for more thorough investigation of the effects of cVNS on gastric bioelectrical slow wave activity and consequential smooth muscle contractions in rats. A better understanding of the effects of cVNS on gastric function will allow the refinement of cVNS therapy to target the stomach, and avoid off-target effects on the stomach.Clinical relevance- This work presents a signal processing and analysis approach for the investigation of cervical vagus nerve stimulation on gastric bioelectrical activity in rats. Vagus nerve stimulation may enable the control and amelioration of hunger, gastric emptying, or functional gastric disorders.

MRI Derived Simulations of Flow Patterns in the Stomach.

A framework to simulate the flow in the stomach using subject-specific motility patterns and geometries was developed. Dynamic 2D magnetic resonance images (MRIs) were obtained. Motility parameters such as contraction speed and occlusion were quantified, and 3D stomach geometries were reconstructed using a semi-automated approach. Computational fluid dynamics (CFD) simulations were performed, and flow patterns were investigated. The stomach of both subjects had distinct anatomical features with computed volumes of 789 mL and 619 mL. For the one subject, the occlusion (i.e., normalized contraction size) was 12% while it was around 25% for the other subject. Contraction speeds were also different (1.9-2.8 mm/s vs 3.0-5.1 mm/s) for each subject. CFD simulations resulted in unsteady laminar flow for both subjects with average velocities of 2.1 and 3.2 mm/s. While antegrade flow was mainly observed in the simulations, a retropulsive jet was also present in both stomachs. The versatile framework developed within this study would allow the generation of CFD models of gastric motility from dynamic MRIs.Clinical Relevance- Subject-specific models of flow patterns informed by gastric motility features can elucidate the impact of contractions and anatomical variations on digestion. Such models can inform therapies to treat gastric dysfunctions and improve their efficacy.

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.

Atrous spatial pyramid pooling and multi-image data fusion for smooth muscle segmentation in upper gastrointestinal sphincters.

Gastrointestinal (GI) sphincters provide critical roles in regulating the transport of contents along the GI tract. Dysfunctions of GI sphincters are associated with a range of major digestive disorders. Despite their importance, the microstructures of GI sphincters are not well investigated. While micro-computed tomography (µ-CT) provides detailed 3D images, conventional segmentation methods rely on manual correction, which is both time-consuming and prone to human error. This study proposes a segmentation method using atrous spatial pyramid pooling (ASPP), which helps in capturing different effective fields of view from a given input feature map, thereof providing finer local and global information for a given pixel. Additionally, we explored the use of multi-species data fusion to make the model more generalized. The proposed segmentation network incorporating ASPP and multi-species data fusion improved the segmentation of sphincter muscle images. Specifically, it increased the dice score and Jaccard index by 3.7% and 5.8%, respectively, while reducing the variance compared to conventional methods.Clinical relevance- Techniques developed in this study will inform µ-CT segmentation of human upper GI sphincters for detailed structural analysis of muscular dysfunction.

Reconstruction of the human lower esophageal sphincter based on ultra-mill imaging for biomechanical analysis.

Introduction: The lower esophageal sphincter (LES) controls the passage into the stomach and prevents reflex of contents into the esophagus. Dysfunctions of this region typically involves impairment of muscular function, leading to diseases including gastro-esophageal reflux disease and achalasia. The main objective of this study was to develop a finite element model from a unique human LES dataset reconstructed from an ultra-mill imaging setup, and then to investigate the effect of anatomical characteristics on intraluminal pressures. Methods: A pipeline was developed to generate a mesh from a set of input images, which were extracted from a unique ultra-mill sectioned human LES. A total of 216 nodal points with cubic Hermite basis function was allocated to reconstruct the LES, including the longitudinal and circumferential muscles. The resultant LES mesh was used in biomechanical simulations, utilizing a previously developed LES mathematical model based on the Visible Human data to calculate intraluminal pressures. Anatomical and functional comparisons were made between the Ultra-mill and Visible human models. Results: Overall, the Ultra-mill model contained lower cavity (1,796 vs. 5,400 mm3) and muscle (1,548 vs. 15,700 mm3) volumes than the Visible Human model. The Ultra-mill model also developed a higher basal pressure (13.8 vs. 14.7 mmHg) and magnitude of pressure (19.8 vs. 18.9 mmHg) during contraction. Out of all the geometric transformations (i.e., uniform enlargement of volume, lengthening along the center-axis, dilation of the diameter, and increasing muscle thickness), the muscle volume was found to be the main contributor of basal and magnitude of pressures. Increases in length also caused proportional increases to pressures, while dilation of diameter had a less influential reverse effect. Discussion: The findings provide information on interindividual variability in LES pressure and demonstrates that anatomy has a large influence on pressures. This model forms the basis of more complex simulations involving food bolus transport and predicting LES dysfunctions.

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.

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.

Diffeomorphic Surface Modeling for MRI-Based Characterization of Gastric Anatomy and Motility.

OBJECTIVE: Gastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the movement of the food inside the stomach, but does not directly report muscular activity on the stomach wall. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the ingesta. METHODS: A neural ordinary differential equation was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomechanical process. Driven by this diffeomorphic flow, the surface of the stomach progressively changes its shape over time, while preserving its topology and manifoldness. RESULTS: We tested this approach with MRI data collected from 10 rats under a lightly anesthetized condition, and demonstrated accurate characterization of gastric motor events with an error in the order of sub-millimeters. Uniquely, we characterized gastric anatomy and motility with a surface coordinate system common at both individual and group levels. Functional maps were generated to reveal the spatial, temporal, and spectral characteristics of muscle activity and its coordination across different regions. The peristalsis at the distal antrum had a dominant frequency and peak-to-peak amplitude of [Formula: see text] cycles per minute and [Formula: see text] mm, respectively. The relationship between muscle thickness and gastric motility was found to be distinct between two functional regions in the proximal and distal stomach. CONCLUSION: These results demonstrate the efficacy of using MRI to model gastric anatomy and function. SIGNIFICANCE: The proposed approach is expected to enable non-invasive and accurate mapping of gastric motility for preclinical and clinical studies.

Computational models of autonomic regulation in gastric motility: Progress, challenges, and future directions.

The stomach is extensively innervated by the vagus nerve and the enteric nervous system. The mechanisms through which this innervation affects gastric motility are being unraveled, motivating the first concerted steps towards the incorporation autonomic regulation into computational models of gastric motility. Computational modeling has been valuable in advancing clinical treatment of other organs, such as the heart. However, to date, computational models of gastric motility have made simplifying assumptions about the link between gastric electrophysiology and motility. Advances in experimental neuroscience mean that these assumptions can be reviewed, and detailed models of autonomic regulation can be incorporated into computational models. This review covers these advances, as well as a vision for the utility of computational models of gastric motility. Diseases of the nervous system, such as Parkinson's disease, can originate from the brain-gut axis and result in pathological gastric motility. Computational models are a valuable tool for understanding the mechanisms of disease and how treatment may affect gastric motility. This review also covers recent advances in experimental neuroscience that are fundamental to the development of physiology-driven computational models. A vision for the future of computational modeling of gastric motility is proposed and modeling approaches employed for existing mathematical models of autonomic regulation of other gastrointestinal organs and other organ systems are discussed.

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.