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.

BackgroundGastrointestinal 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.ResultsGEMS 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).ConclusionsThis 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.

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.

The aim of this study was to combine the anatomy and physiology of the human gastroesophageal junction (the junction between the esophagus and the stomach) into a unified computer model. A three-dimensional computer model of the gastroesophageal junction was created using crosssectional images from a human cadaver. The governing equations of finite deformation elasticity were incorporated into the three-dimensional model. The model was used to predict the intraluminal pressure values (pressure inside the junction) due to the muscle contraction of the gastroesophageal junction and the effects of the surrounding structures. The intraluminal pressure results obtained from the three-dimensional model were consistent with experimental values available in the literature. The model was also used to examine the independent roles of each muscle layer (circular and longitudinal) of the gastroesophageal junction by contracting them separately. Results showed that the intraluminal pressure values predicted by the model were primarily due to the contraction of the circular muscle layer. If the circular muscle layer was quiescent, the contraction of the longitudinal muscle layer resulted in an expansion of the junction.In conclusion, the model provided reliable predictions of the intraluminal pressure values during the contraction of a normal gastroesophageal junction. The model also provided a framework to examine the role of each muscle layer during the contraction of the gastroesophageal junction.

The aim of this study was to obtain detailed information regarding the three-dimensional structure of the gastro-oesophageal region, and, in particular, the fiber orientation of the different muscle layers of the junction. This was achieved by a study of an en bloc resection of the gastro-oesophageal junction (GOJ) harvested from a human cadaver. The excised tissue block was suspended in a cage to preserve anatomical relationships, fixed in formalin and embedded in wax. The tissue block was then processed by a custom-built extended-volume imaging system to obtain the microstructural information using a digital camera which acquires images at a resolution of 8.2 μm/pixel. The top surface of the tissue block was sequentially stained and imaged. At each step, the imaged surface was milled off at a depth of 50 μm. The processing of the tissue block resulted in 650 images covering a length of 32.25 mm of the GOJ. Structures, including the different muscle and fascial layers, were then traced out from the cross-sectional images using color thresholding. The traced regions were then aligned and assembled to provide a three-dimensional representation of the GOJ. The result is the detailed three-dimensional microstructural anatomy of the GOJ represented in a new way. The next stage will be to integrate key physiological events, including peristalsis and relaxation, into this model using mathematical modeling to allow accurate visual tools for training health professionals and patients.