A Stochastic Multi-Scale Model of Electrical Function in Normal and Depleted ICC Networks

Abstract

Multi-scale modeling has become a productive strategy for quantifying interstitial cells of Cajal (ICC) network structure-function relationships, but the lack of large-scale ICC network imaging data currently limits modeling progress. The SNESIM (Single Normal Equation Simulation) algorithm was utilized to generate realistic virtual images of small real wild-type (WT) and 5-HT2B-receptor knockout (Htr2b−/−) mice ICC networks. Two metrics were developed to validate the performance of the algorithm: (i) network density, which is the proportion of ICC in the tissue; (ii) connectivity, which reflects the degree of connectivity of the ICC network. Following validation, the SNESIM algorithm was modified to allow variation in the degree of ICC network depletion. ICC networks from a range of depletion severities were generated, and the electrical activity over these networks was simulated. The virtual ICC networks generated by the original SNESIM algorithm were similar to that of their real counterparts. The electrical activity simulations showed that the maximum current density magnitude increased as the network density increased. In conclusion, the SNESIM algorithm is an effective tool for generating realistic virtual ICC networks. The modified SNESIM algorithm can be used with simulation techniques to quantify the physiological consequences of ICC network depletion at various physical scales.

Cellular automaton model for simulating tissue-specific intestinal electrophysiological activity

“…However, the functional significance of ICC depletion remains speculative, partly due to the lack of methods for quantitatively analyzing ICC structure-function relationships. To address this issue, we previously developed numerical metrics to quantify structural properties of ICC networks [11], and now further techniques for relating the quantified structure to function is required.…”

“…Previous studies have simulated tissue-specific slow wave propagation over ICC networks by coupling imaging data with a modified biophysically-based Corrias and Buist cell model [12] embedded within a continuum modeling framework [11, 13]. However, this methodology is computationally expensive [13], mainly due to the large number of equations and parameters present in the cell model, and hence difficulties exist in up-scaling these simulations to larger multiscale simulation studies.…”

Numerical metrics for automated quantification of interstitial cell of Cajal network structural properties

“…The functional significance of the potential remodelling and pruning phenomena discussed here could be investigated using mathematical simulation techniques, whereby the network structures are coupled to an electrical activity modelling framework and embedded biophysically based cell models, as previously demonstrated in GI tissue-specific modelling studies [20,25]. The simulated slow wave propagation across ICC networks could then be correlated to the structural changes observed in the confocal images.…”

“…Two of the six metrics (density and connectivity) were described in a preliminary form in an earlier report by Gao et al [20]. The metrics were inspired by and partly adapted from existing methods of quantifying structure from alternative fields [21,22].…”

Developmental Changes in Postnatal Murine Intestinal Interstitial Cell of Cajal Network Structure and Function

“…This study therefore aimed to identify, quantify, and characterize structural changes in ICC network imaging data acquired at multiple ages throughout early postnatal life to test the presence of a pruning-like mechanism, and to elucidate the temporal course of this process. In addition, biophysically-based computational simulations of ICC pacemaker activity over the imaged ICC networks 3,8 were performed to gain quantitative insights into the functional significance of the identified structural changes.…”