The virtual esophagus: investigating esophageal functions in silico.

Esophageal and gastroesophageal junction (GEJ) diseases are highly prevalent worldwide and are a significant socioeconomic burden. Recently, applications of multiscale mathematical models of the upper gastrointestinal tract have gained attention. These in silico investigations can contribute to the development of a virtual esophagus modeling framework as part of the larger GIome and Physiome initiatives. There are also other modeling investigations that have potential screening and treatment applications. These models incorporate detailed anatomical models of the esophagus and GEJ, tissue biomechanical properties and bolus transport, sensory properties, and, potentially, bioelectrical models of the neural and myogenic pathways of esophageal and GEJ functions. A next step is to improve the integration between the different components of the virtual esophagus, encoding standards, and simulation environments to perform more realistic simulations of normal and pathophysiological functions. Ultimately, the models will be validated and will provide predictive evaluations of the effects of novel endoscopic, surgical, and pharmaceutical treatment options and will facilitate the clinical translation of these treatments.

The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail.

BACKGROUND: Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail. RESULTS: GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user-friendly graphical user interface. GEMS is implemented using MATLAB®, which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (http://sites.google.com/site/gimappingsuite). CONCLUSIONS: This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping.

Tissue-specific mathematical models of slow wave entrainment in wild-type and 5-HT(2B) knockout mice with altered interstitial cells of Cajal networks.

Gastrointestinal slow waves are generated within networks of interstitial cells of Cajal (ICCs). In the intact tissue, slow waves are entrained to neighboring ICCs with higher intrinsic frequencies, leading to active propagation of slow waves. Degradation of ICC networks in humans is associated with motility disorders; however, the pathophysiological mechanisms of this relationship are uncertain. A recently developed biophysically based mathematical model of ICC was adopted and updated to simulate entrainment of slow waves. Simulated slow wave propagation was successfully entrained in a one-dimensional model, which contained a gradient of intrinsic frequencies. Slow wave propagation was then simulated in tissue models which contained a realistic two-dimensional microstructure of the myenteric ICC networks translated from wild-type (WT) and 5-HT(2B) knockout (degraded) mouse jejunum. The results showed that the peak current density in the WT model was 0.49 muA mm(-2) higher than the 5-HT(2B) knockout model, and the intracellular Ca(2+) density after 400 ms was 0.26 mM mm(-2) higher in the WT model. In conclusion, tissue-specific models of slow waves are presented, and simulations quantitatively demonstrated physiological differences between WT and 5-HT(2B) knockout models. This study provides a framework for evaluating how ICC network degradation may impair slow wave propagation and ultimately motility and transit.

Modelling gastrointestinal bioelectric activity.

The development of an anatomically realistic biophysically based model of the human gastrointestinal (GI) tract is presented. A major objective of this work is to develop a modelling framework that can be used to integrate the physiological, anatomical and medical knowledge of the GI system. The anatomical model was developed by fitting derivative continuous meshes to digitised data taken from images of the visible man. Structural information, including fibre distributions of the smooth muscle layers and the arrangement of the networks of interstitial cells of Cajal, were incorporated using published information. A continuum modelling framework was used to simulate electrical activity from the single cell to the whole organ and body. Also computed was the external magnetic field generated from the GI electrical activity. The set of governing equations were solved using a combination of numerical techniques. Activity at the (continuum) cell level was solved using a high-resolution trilinear finite element procedure that had been defined from the previously fitted C1 continuous anatomical mesh. Multiple dipolar sources were created from the excitation waves which were embedded within a coupled C1 continuous torso model to produce both the cutaneous electrical field and the external magnetic field. Initial simulations were performed using a simplified geometry to test the implementation of the numerical solution procedure. The numerical procedures were shown to rapidly converge with mesh refinement. In the process of this testing, errors in a long standing analytic solution were identified and are corrected in Appendix B. Results of single cell activity were compared to published results illustrating that the key features of the slow wave activity were successfully replicated. Simulations using a two-dimensional slice through the gastric wall produced slow wave activity that agreed with the known frequency and propagation characteristics. Three-dimensional simulations were also performed using the full stomach mesh and results illustrated the slow wave propagation throughout the stomach musculature.