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.

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy.

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20-30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency 'slow wave' which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

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.

Biomimetic Closed-Loop Control of a Novel Soft Gastric Simulator Toward Emulating Antral Contraction Waves.

Soft gastric simulators are in vitro biomimetic modules that can reproduce the antral contraction waves (ACWs). Along with providing information concerning stomach contents, stomach simulators enable experts to evaluate the digestion process of foods and drugs. Traditionally, open-loop control approaches were implemented on stomach simulators to produce ACWs. Constructing a closed-loop control system is essential to improve the simulator's ability to imitate ACWs in additional scenarios and avoid constant tuning. Closed-loop control can enhance stomach simulators in accuracy, responding to various food and drug contents, timing, and unknown disturbances. In this article, a new generation of anatomically realistic soft pneumatic gastric simulators is designed and fabricated. The presented simulator represents the antrum, the lower portion of the stomach where ACWs occur. It is equipped with a real-time feedback system to implement diverse closed-loop controllers on demand. All the details of the physical design, fabrication, and assembly process are discussed. Also, the measures taken for the mechatronics design and sensory system are highlighted in this article. Through several implementation algorithms and techniques, three closed-loop controllers, including model-based and model-free schemes are designed and successfully applied on the presented simulator to imitate ACWs. All the experimental outcomes are carefully analyzed and compared against the biological counterparts. It is demonstrated that the presented simulator can serve as a reliable tool and method to scrutinize digestion and promote novel technologies around the human stomach and the digestion process. This research methodology can also be utilized to develop other biomimetic and bioinspired applications.

A Review of In Vitro and In Silico Swallowing Simulators: Design and Applications.

Swallowing is a primary and complex behaviour that transports food and drink from the oral cavity, through the pharynx and oesophagus, into the stomach at an appropriate rate and speed. To understand this sophisticated behaviour, a tremendous amount of research has been carried out by utilising the in vivo approach, which is often challenging to perform, poses a risk to the subjects if interventions are undertaken and are seldom able to control for confounding factors. In contrast, in silico (computational) and in vitro (instrumental) methods offer an alternate insight into the process of the human swallowing system. However, the appropriateness of the design and application of these methods have not been formally evaluated. The purpose of this review is to investigate and evaluate the state of the art of in vitro and in silico swallowing simulators, focusing on the evaluation of their mechanical or computational designs in comparison to the corresponding swallowing mechanisms during various phases of swallowing (oral phase, pharyngeal phase and esophageal phase). Additionally, the potential of the simulators is also discussed in various areas of applications, including the study of swallowing impairments, swallowing medications, food process design and dysphagia management. We also address current limitations and recommendations for the future development of existing simulators.

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.

An Accurate Fiducial Marker for Aligning EMG signals with Swallow Onset.

Swallowing involves the precise coordination of a large number of muscles. This coordination can be quantified non-invasively by electromyographic (EMG) time-series analysis of swallowing events. The temporal alignment of swallow events is critical for defining coordination patterns. Here, a new framework was developed to use the acoustic signal associated with the opening of the Eustachian tube as a fiducial marker to align EMG signals with swallowing. To investigate its accuracy, manometry, audio from the Eustachian tube, and EMG were simultaneously recorded from two participants while performing different swallowing maneuvers. Eustachian tube opening consistently occurred alongside EMG activations and within 0.025 ± 0.022 s of the gold standard manometry-determined functional swallowing onset. A comparison with two traditional EMG alignment methods based on the integrated and rectified EMG signals was then performed over eight participants. Discrepancies of between 0.2 to 0.3 s were found between the initiation of swallowing and the onset or peak EMG activity. Eustachian tube opening served as a more accurate fiducial marker for temporal data alignment, compared to the traditional EMG alignment methods that were based on EMG parameters.Clinical Relevance- The proposed method will allow EMG recordings to be directly associated with the functional onset of swallowing. This provides a more accurate foundation for time-series analysis of muscle coordination and thus the identification of EMG biomarkers associated with healthy and dysphagic swallowing.

Optical Mapping of Virtual Electrode Polarization Pattern and Its Relationship with Pacemaker Location during Gastric Pacing.

Gastric rhythmic contractions are regulated by bioelectrical events known as slow waves (SW). Abnormal SW activity is associated with gastric motility disorders. Gastric pacing is a potential treatment method to restore rhythmic SW activity. However, to date, the efficacy of gastric pacing is inconsistent and the underlying mechanisms of gastric pacing are poorly understood. Optical mapping is widely used in cardiac electrophysiology studies. Its immunity to pacing artifacts offers a distinct advantage over conventional electrical mapping for studying pacing. In the present study, we first found that optical mapping can image pacing-induced virtual electrode polarization patterns in the stomach (adjacent regions of depolarized and hyperpolarized tissue). Second, we found that elicited SWs usually (15 of 16) originated from the depolarized areas of the stimulated region (virtual cathodes). To our knowledge, this is the first direct observation of virtual electrode polarization patterns in the stomach. Conclusions: Optical mapping can image virtual electrode polarization patterns during gastric pacing with high spatial resolution.Clinical Relevance- Gastric pacing is a potential therapeutic method for gastric motility disorders. This study provides direct observation of virtual electrode polarization pattern during gastric pacing and improves our understanding of the mechanisms underlying gastric pacing..

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.

Landmark-free Shape Analysis of the Human Duodenum.

The primary function of the duodenum is to undertake chemical digestion by ensuring that the partially digested food received from the stomach is well-mixed with the enzymes and chemicals secreted into it. However, little is known about the anatomical variations in the shape of the duodenum within humans, and thus the effect of duodenum shape on the flow and mixing occurring within the lumen has not been studied. In this work, a methodology for analyzing shape variations in the normal duodenal anatomy has been developed and applied to a publicly available dataset of abdominal CT images. This method does not require the placement of landmarks as it is based on the underlying tubular 'C' shape of the duodenum. The average duodenal length and radius of this dataset (consisting of 34 subjects) were 212.8 ± 38 mm and 10.8 ± 2.5 mm respectively. A Principal Component Analysis (PCA) was conducted on a sample of 34 duodenums after normalizing their lengths and the first five principal components were found to contribute to 82 % of the total variation. The first shape component (accounting for 42 % of overall variation) consisted of variations in the radius along the duodenum with no deformations normal to the central plane, and the subsequent shape modes consisted of twists in the centerline either in and out of the central plane, and radial variations at either the inlet or outlet. This is the first study to analyze shape variations in the human duodenum and the results can be combined with flow modeling to analyze the effect of shape on the flow and mixing occurring within the duodenum.Clinical relevance- The methods developed in this study can be used by clinicians to diagnose abnormalities in an individual's duodenum shape.

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.

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

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

Smart capsules for sensing and sampling the gut: status, challenges and prospects.

Smart capsules are developing at a tremendous pace with a promise to become effective clinical tools for the diagnosis and monitoring of gut health. This field emerged in the early 2000s with a successful translation of an endoscopic capsule from laboratory prototype to a commercially viable clinical device. Recently, this field has accelerated and expanded into various domains beyond imaging, including the measurement of gut physiological parameters such as temperature, pH, pressure and gas sensing, and the development of sampling devices for better insight into gut health. In this review, the status of smart capsules for sensing gut parameters is presented to provide a broad picture of these state-of-the-art devices while focusing on the technical and clinical challenges the devices need to overcome to realise their value in clinical settings. Smart capsules are developed to perform sensing operations throughout the length of the gut to better understand the body's response under various conditions. Furthermore, the prospects of such sensing devices are discussed that might help readers, especially health practitioners, to adapt to this inevitable transformation in healthcare. As a compliment to gut sensing smart capsules, significant amount of effort has been put into the development of robotic capsules to collect tissue biopsy and gut microbiota samples to perform in-depth analysis after capsule retrieval which will be a game changer for gut health diagnosis, and this advancement is also covered in this review. The expansion of smart capsules to robotic capsules for gut microbiota collection has opened new avenues for research with a great promise to revolutionise human health diagnosis, monitoring and intervention.

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.

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.