Guest speaker

Cardiac Modeling and the Physiome Project

Poul Nielsen and Peter Hunter
Bioengineering Institute, University of Auckland, New Zealand

Abstract

The Physiome Project is an attempt to build a comprehensive framework for computational modeling of human biochemistry, biophysics and anatomy. The goal of this project, sponsored by the International Union of Physiological Sciences (IUPS) and the IEEE Engineering in Medicine and Biology Society (EMBS), is to use computational modeling to analyze integrative physiological function in terms of underlying biological structure and processes. Web-accessible databases of model-related data at the organ system, organ, tissue and cellular levels have been established to support the project. These databases currently include quantitative descriptions of anatomy, mathematical characterisations of physiological processes and associated bibliographic information.

The Physiome Project offers those involved in medical imaging and computer-assisted intervention an opportunity to contribute to an open collaborative effort to provide readily accessible quantitative physiological and anatomical information. It also provides an opportunity for this community to use such information to further combine computational modeling with biophysically-based interpretation of images and robot-assisted surgery devices. The challenge for the Physiome Project is to link the revolution in the medical imaging of structure and function with the genomics and proteomics revolution using computational modeling tailored to the anatomy, physiology and genetics of the individual. In order to achieve this we require the development of comprehensive databases covering a wide range of spatial and temporal scales, linked by models (so that the parameters of larger-scale models are supported by quantitative experiments and models at finer scales) and ontologies (so that concepts associated with different bodies of knowledge may be expressed formally, related to one another and checked for consistency). Modeling the heart provides an illustrative example of how the Physiome Project can achieve these goals.

The human heart is an anatomically and biophysically complicated organ. In order to make accurate predictions of cardiac performance any model of heart mechanics must be based upon the highly nonlinear partial differential equations associated with large deformations of soft tissue, a detailed description of myocardial architecture and a characterisation of the passive and active multiaxial properties of the myocardium. While the mathematics and computational aspects of large deformation mechanics is well understood the architectural and constitutive aspects of heart modeling are relatively poorly supported.

To address this problem the publicly accessible Physiome database includes quantitative descriptions of ventricular geometry, muscle fibre and cleavage plane orientation, as well as the embeddings of Purkinje fibres and coronary vessels, all based upon detailed experimental measurements. Furthermore, extensive measurements of myocardial microstructure provide the small-scale architectural information required to model the wavefront of muscle activation past cleavage planes, thus enabling large scale phenomena (such as average activation velocity) to be quantitatively related to large-scale architectural details. We are currently using models of cardiac mechanics, based upon the above principles and enabled by the information stored within the Physiome database, to accurately predict the electro mechanics of cardiac contraction.

This integrative approach has allowed us to couple models of different processes (coronary flow and ventricular fluid dynamics with myocardial mechanics), as well as hierarchically nest models of different scales (cellular ionic flow with ventricular excitation-contraction and torso-level electrodynamics), providing flexible and powerful tools to investigate cardiac performance.

Biography

Dr. Poul Nielsen received his B.Sc. in physics and mathematics in 1978 and a BE (Hons) in engineering science in 1981 from the University of Auckland NZ. He obtained his PhD (modeling cardiac architecture) from the University of Auckland in 1987 and spent two years as a postdoctoral fellow in the biomedical engineering department at McGill University.

Since 1990 he has been a senior lecturer within engineering science and the Bioengineering Institute at the University of Auckland. Over the past several decades he has been extensively involved with his colleague Prof. Peter Hunter on leading edge developments within the Physiome project. This work represents a worldwide public domain effort to provide a computational framework for understanding human physiology. It aims to develop integrative models at all levels of biological organization, from genes to the whole organism via gene regulatory networks, protein pathways, integrative cell function, and tissue and whole organ structure/function relations.