A computationally efficient anisotropic electrophysiological multiscale uterus model: From cell to organ and myometrium to abdominal surface

Background and objective: Preterm labor is a global problem affecting the health of newborns. Despite numerous studies reporting electrophysiological changes throughout pregnancy, the underlying mechanism that triggers labor remains unclear. Electrophysiological modeling can provide additional information to better understand the physiological transition from pregnancy to labor. Previous uterine electrophysiological models do not consider either the tissue thickness or fiber structure, which have both been shown to significantly impact propagation patterns.

Methods: This paper presents a parallel computational model of the uterus using the bioengineering modeling environment OpenCMISS. This model is a multiscale anisotropic model that spans different levels from cell to organ. At the cellular level, the model utilizes a mathematical representation of uterine myocytes based on multiple ion channels. In the 3D uterine model, fiber structures are added, ranging from horizontal rings in the inner layer to vertically downward fibers in the outer layer, to more accurately depict the electrophysiological activities of the uterus. Additionally, we have developed a multilayer volume conduction model based on the boundary element method to describe the propagation of electrical signals from the myometrium to the abdominal surface.

Results: Our model can not only reproduce faithfully both local non-propagated and global propagated electrical activity, but also simulate the fast wave low and fast wave high components of the electrohysterogram (EHG) on the abdominal surface. The model results support the hypothesis that the fast wave high of the EHG signal is related to uterine excitability and fast wave low is related to signal propagation. The amplitude of the simulated signal on the abdominal surface falls in the ranges of real EHG data, which is inversely proportional to the abdominal subcutaneous fat thickness, and the signal waveform highly depends on electrode position and the relative distance to the pacemaker. In addition, the propagation velocity is highly dependent on the uterus geometry and falls in the real-world data range CONCLUSIONS: Our models facilitate a better understanding of the electrophysiological changes of the uterus during pregnancy and labor, and allow for an investigation of drug effects and/or structural or anatomical abnormalities.