Project: Biophysical Modelling of the Uterine Electromyogram for understanding and preventing PreTerm Labor

The aim of the BioMod UE_PTL project is to better understand the links existing between the microscopic phenomenon involved in uterine contractility leading to labour and the macroscopic electrical activity observed on the abdomen of pregnant women, the electrohysterogram (EHG). The ultimate goal is to provide the knowledge to create a clinical tool that can detect the presence of pathological uterine contractility leading to preterm labour. The uterus is a very complex and dynamic system, which is controlled by hormonal environment as well as by electric and mechanical feedbacks. Many open questions remain regarding the actual mechanisms leading to onset of labour. The only way to address these questions is through multiscale modeling starting at the biological phenomenon involved in individual uterine cell contractility, leading to the generation of EHG on the abdomen. The model will work as a tool to increase our understanding of the uterine contractile system, to validate or invalidate previously raised hypothesis, and finally to permit the development of tools specific for the prediction of preterm labour. It will integrate the generation of contractile activity at the cell level, communication in bundles of cells, and propagation to the whole organ and to the abdomen, through the complex conduction volume. The data, acquired from animal and human experiments, will be used to create a model of the behaviour of the uterus. The results obtained from the models will then be used to guide experimentation and to model the effects of pharmacological agents on the uterus. Apart from disseminating results in the classical manner for scientific and technical research, a separate aim of the project is to develop means to share data and results, both between the partners and with the larger scientific community. As far as we know, there are no data standards for smooth muscle EMG and EHG digital recordings and preterm delivery models. These standards will be developed and set as best practice by the project consortium.

Acronym	BioMod UE-PTL
Project Results (after finalisation)	In Europe, preterm birth (5% to 12% of total births) is a major cause of perinatal mortality and morbidity. Unfortunately, current obstetrical practice cannot accurately predict the risk of preterm labour. The uterus is a complex system, controlled by intricate hormonal mechanisms and feedbacks. Furthermore, important physiological phenomena involving uterine contractility and the onset of preterm labor are not yet fully understood. A promising non-invasive technique for studying uterine contractility is the electrohysterogram (EHG). The EHG represents the electrical trigger of the mechanical uterine contraction and it can be recorded on the woman's abdomen. Different teams have previously investigated the EHG evolution relative to term and preterm labor, focusing on cell excitability and electrical activity propagation. However, the only possible way to understand uterine contractility is through a mathematical multiscale modelling, by using a system biology approach. The aim of this project is thus to develop a multiscale model to improve understanding of the link between the microscopic phenomena involved in uterine contractility and the macroscopic electrical uterine activity recorded by EHG. Model development: We first simplified a previously developed model of the uterine cell, in order to reduce the computational time while keeping the link with the physiology. We then modelled the propagation at the tissue level in 2 dimensions, for a flat surface with thickness, and in 3 dimensions, for a shape representative of uterine geometry. Finally, the specific anatomy of pregnant woman's abdomen was modeled, including skeletal muscle, fat and skin, in order to allow simulating the EHG recorded by a given electrode configuration. Furthermore, dedicated EHG and ultrasound measurements have been performed to analyze the effects of uterine movement artifacts on the EHG signals. After quantification of the mechanical properties of these movements, different simulations permitted the first characterization of their effects on the EHG. Recording protocol and signal data base: An EHG signal portal and a database needed for model validation were designed in agreement with the whole consortium. Signals were recorded according to a common EHG protocol, which was standardized and used by all partners. This database will be made available to the EU and global scientific community through a portal. Conclusion and perspectives: The developed model involves several stages from the cell level modelling to the recording of the EHG on the abdomen. A sensitivity analysis is currently being performed in order to evidence the EHG processing feature that will permit the identification of unknown parameters. This model will further be used to develop a model-aided diagnostic tool for the detection of preterm labour.
Network	ERASysBio+
Call	ERASysBio+-2008-01

Project partner

Number	Name	Role	Country
1	Université de Technologie de Compiègne	Coordinator	France
2	Centre de recherches commun CEA/INSERM MIRCen	Partner	France
3	Technological University Eindhoven	Partner	Netherlands
4	Máxima Medical Centre	Partner	Netherlands
5	University of Ljubljana	Partner	Slovenia
6	Reykjavik University	Observer	Iceland
7	Tms International	Partner	Netherlands