Experimental progress in investigating normal and disordered gastric motility is increasingly being complimented by sophisticated multi-scale modeling studies. Mathematical modeling has become a valuable tool in this effort, as there is an ever-increasing need to gain an integrative and quantitative understanding of how physiological mechanisms achieve coordinated functions across multiple biophysical scales. These interdisciplinary efforts have been particularly notable in the area of gastric electrophysiology, where they are beginning to yield a comprehensive and integrated in-silico organ modeling framework, or ‘virtual stomach’. At the cellular level, a number of biophysically-based mathematical cell models have been developed, and these are now being applied in areas including investigations of gastric electrical pacemaker mechanisms, smooth muscle electrophysiology, and electromechanical coupling. At the tissue level, micro-structural models are being creatively developed and employed to investigate clinically significant questions, such as the functional effects of ICC degradation on gastrointestinal electrical activation. At the organ level, high-resolution electrical mapping and modeling studies are combining to provide improved insights into normal and dysrhythmic gastric electrical activation. These efforts are also enabling detailed forward and inverse modeling studies at the ‘whole body’ level, with implications for diagnostic techniques for gastric dysrhythmias. These recent advances, together with several others highlighted in this review, collectively demonstrate a powerful trend toward applying mathematical models to effectively investigate structure-function relationships and overcome multi-scale challenges in basic and clinical gastrointestinal research.

Background Gastric motility is coordinated by bioelectrical slow-waves, and gastric dysrhythmias are reported in motility disorders. High-resolution (HR) mapping has advanced the accurate assessment of gastric dysrhythmias, offering promise as a diagnostic technique. However, HR mapping has been restricted to invasive surgical serosal access. This study investigates the feasibility of HR mapping from the gastric mucosal surface. Methods Experiments were conducted in-vivo in 14 weaner pigs. Reference serosal recordings were performed with flexible-printed-circuit (FPC) arrays (128-192 electrodes). Mucosal recordings were performed by two methods: 1) FPC array aligned directly opposite the serosal array, and 2) cardiac mapping catheter modified for gastric mucosal recordings. Slow-wave propagation and morphology characteristics were quantified and compared between simultaneous serosal and mucosal recordings. Key Results Slow-wave activity was consistently recorded from the mucosal surface from both electrode arrays. Mucosally-recorded slow-wave propagation was consistent with reference serosal activation pattern, frequency (P≥0.3), and velocity (P≥0.4). However, mucosally-recorded slow-wave morphology exhibited reduced amplitude (65-72% reduced, P<0.001) and wider downstroke width (18-31% wider, P≤0.02), compared to serosal data. Dysrhythmias were successfully mapped and classified from the mucosal surface, accorded with serosal data, and were consistent with known dysrhythmic mechanisms in the porcine model. Conclusions & Inferences HR gastric electrical mapping was achieved from the mucosal surface, and demonstrated consistent propagation characteristics with serosal data. However, mucosal signal morphology was attenuated, demonstrating necessity for optimized electrode designs and analytical algorithms. This study demonstrates feasibility of endoscopic HR mapping, providing a foundation for advancement of minimally-invasive spatiotemporal gastric mapping as a clinical and scientific tool.

Background High-resolution (HR) extracellular mapping allows accurate profiling of normal and dysrhythmic slow wave patterns. A current limitation is that cables traverse the abdominal wall or a natural orifice, risking discomfort, dislodgement or infection. Wireless approaches offer advantages, but a multi-channel system is required, capable of recording slow waves and mapping propagation with high fidelity. Methods A novel multi-channel (n=7) wireless mapping system was developed and compared to a wired commercial system. Slow wave signals were recorded from the porcine gastric and intestinal serosa in-vivo. Signals were simultaneously acquired using both systems, and were filtered and processed to map activation wavefronts. For validation, the frequency and amplitude of detected events were compared, together with the speed and direction of mapped wavefronts. Key Results The wireless device achieved comparable signal quality to the reference device, and slow wave frequencies were identical. Amplitudes of the acquired gastric and intestinal slow wave signals were consistent between the devices. During normal propagation, spatiotemporal mapping remained accurate in the wireless system, however, during ectopic dysrhythmic pacemaking, the lower sampling resolution of the wireless device led to reduced accuracy in spatiotemporal mapping. Conclusions and Inferences A novel multichannel wireless device is presented for mapping slow wave activity. The device achieved high quality signals, and has the potential to facilitate chronic monitoring studies and clinical translation of spatiotemporal mapping. The current implementation may be applied to detect normal patterns and dysrhythmia onset, but HR mapping with finely spaced arrays currently remains necessary to accurately define dysrhythmic patterns.

Gastrointestinal (GI) motility is regulated in part by electrophysiological events called slow waves, which are generated by the interstitial cells of Cajal (ICC). Slow waves propagate by a process of “entrainment,” which occurs over a decreasing gradient of intrinsic frequencies in the antegrade direction across much of the GI tract. Abnormal initiation and conduction of slow waves have been demonstrated in, and linked to, a number of GI motility disorders. A range of mathematical models have been developed to study abnormal slow waves and applied to propose novel methods for non-invasive detection and therapy. This review provides a general outline of GI slow wave abnormalities and their recent classification using multi-electrode (high-resolution) mapping methods, with a particular emphasis on the spatial patterns of these abnormal activities. The recently-developed mathematical models are introduced in order of their biophysical scale from cellular to whole-organ levels. The modeling techniques, main findings from the simulations, and potential future directions arising from notable studies are discussed.

Gastrointestinal motility is coordinated by slow waves (SWs) generated by the interstitial cells of Cajal (ICC). Experimental studies have shown that SWs spontaneously activate at different intrinsic frequencies in isolated tissue, whereas in intact tissues they are entrained to a single frequency. Gastric pacing has been used in an attempt to improve motility in disorders such as gastroparesis by modulating entrainment, but the optimal methods of pacing are currently unknown. Computational models can aid in the interpretation of complex in-vivo recordings and help to determine optical pacing strategies. However, previous computational models of SW entrainment are limited to the intrinsic pacing frequency as the primary determinant of the conduction velocity, and are not able to accurately represent the effects of external stimuli and electrical anisotropies. In this paper, we present a novel computationally efficient method for modelling SW propagation through the ICC network while accounting for conductivity parameters and fiber orientations. The method successfully reproduced experimental recordings of entrainment following gastric transection and the effects of gastric pacing on SW activity. It provides a reliable new tool for investigating gastric electrophysiology in normal and diseased states, and to guide and focus future experimental studies.