Abstract:
We have developed a computational modelling and simulation framework for cardiac electromechanics
which for the first time tightly couples cellular, tissue, and whole heart modelling
paradigms. Application of the framework has been demonstrated in simulations of the electrical
activation and mechanical contraction of cardiac myocytes, myocardial tissue, and models of
ventricular structure and function.
The framework has been implemented as part of the CMISS computational modelling environment.
This allows for detailed specification of tissue microstructure and the variation of
cellular models and their material parameters over a geometric domain of interest. Through
previous work in CMISS we have access to a large pool of existing models and methods on
which to base this work.
A key aspect of our framework is the implementation of methods allowing the dynamic
specification of mathematical models at run-time using CellML – an XML language designed
to store and exchange computer based biological models. We use these methods to enable the
specification of cellular level models using CellML, thus providing a very powerful method to
simply “plug” cellular models into the distributed tissue and organ level models. While in this
work we have developed specific cellular models, and their CellML description, the framework
is now developed to the point where a non-expert user could pull out a given model and plug-in
their own model. This allows cellular modellers to develop their models and then bring them
into a distributed model of tissue or organ physiology.
We present a review of cellular electrophysiology and mechanics models. As a demonstration
of the ability of CellML to describe cardiac cellular models in a computationally useful
manner we have encoded the majority of these models into CellML. The CellML descriptions of
these models are provided as they were used in the computational simulations which generated
all results presented for the models directly from the CellML encoded models. While the work described in this thesis focuses on cardiac electro-mechanics, the framework
has much wider applicability. As such, this work forms the beginning of a generalised
simulation framework for the IUPS Physiome Project, with the goal being models describing
entire organisms from proteins through to organ systems.
