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WIREs Syst Biol Med
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Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility

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Abstract Experimental progress in investigating normal and disordered gastric motility is increasingly being complimented by sophisticated multiscale 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 (GI) electrical activation. At the organ level, high‐resolution electrical mapping and modeling studies are combined 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 multiscale challenges in basic and clinical GI research. WIREs Syst Biol Med 2013, 5:481–493. doi: 10.1002/wsbm.1218 This article is categorized under: Models of Systems Properties and Processes > Cellular Models Translational, Genomic, and Systems Medicine > Diagnostic Methods Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

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Multiscale arrangement of GI electrophysiological models. The spatial scales cover cellular to whole body levels. The electrophysiological process at each spatial scale can also be over different temporal scales, from milliseconds to hours.

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Simulated body surface potential fields (colored field) and magnetic vector fields located at an array above the stomach region (yellow arrows) due to an instance of gastric slow wave activity (as shown in Figure ).

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Gastric slow wave propagation simulated in a virtual human stomach model. The sequence of slow wave activations shows that slow waves originate from a pacemaker on the greater curvature of the proximal stomach and then propagates in the antegrade direction toward the gastric pylorus.

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ICC networks and slow wave propagation. (a) Virtual ICC networks were generated using an adapted SNESIM algorithm with varying degrees of ICC densities in the image field (636 × 636 µm), at 35, 40, 45, and 50% density (normal network density). The generated ICC networks are four times the area of the real ICC network image (318 × 318 µm). (b) Demonstration of slow wave entrainment simulations in a real depleted ICC network (≈︁35% density) over 120 ms.

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ICC pathway simulations. (a) A two‐layer model consisting of ICC‐MP and circular ICC‐IM networks. The ICC‐MP layer conductivity was homogenous, while the ICC‐IM layer conductivity was preferentially in the circumferential fiber direction. (b) Ectopic pacemaking with ICC‐IM decoupled from the ICC‐MP (shown). Slow waves propagated homogenously in all directions. (c) Ectopic pacemaking with ICC‐IM bidirectionally coupled to the ICC‐MP (shown). ICC‐IM assumed the driving network role during circumferential conduction, outpacing and activating ICC‐MP, while slower longitudinal conduction occurred through ICC‐MP.

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Cell model simulations of gastrointestinal slow wave activity. (a) An intestinal ICC model developed by Faville et al. (b) Gastric ICC (solid line) and SMC (dashed line) model developed by Corrias and Buist. (c) An intestinal SMC model developed by Poh et al. (d) A gastric electromechanical model developed by Gajendiran et al. showing the relationship between intracellular Ca2+ (solid line) and normalized force generation (dashed line) in a SMC.

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Models of Systems Properties and Processes > Cellular Models
Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Translational, Genomic, and Systems Medicine > Diagnostic Methods

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