Biomedical subjects
Peter Hunter
Publications and source records attributed to Peter Hunter.
New developments in a strongly coupled cardiac electromechanical model.
AIM: The aim of this study is to develop a coupled three-dimensional computational model of cardiac electromechanics to investigate fibre length transients and the role of electrical heterogeneity in determining left ventricular function. METHODS: A mathematical model of cellular electromechanics was embedded in a simple geometric model of the cardiac left ventricle. Electrical and mechanical boundary conditions were applied based on Purkinje fibre activation times and ventricular volumes through the heart cycle. The mono-domain reaction diffusion equations and finite deformation elasticity equations were solved simultaneously through the full pump cycle. Simulations were run to assess the importance of cellular electrical heterogeneity on myocardial mechanics. RESULTS: Following electrical activation, mechanical contraction moves out through the wall to the circumferentially oriented mid-wall fibres, producing a progressively longitudinal and twisting deformation. This is followed by a more spherical deformation as the inclined epicardial fibres are activated. Mid-way between base and apex peak tensions and fibre shortening of 40 kPa and 5%, respectively, are generated at the endocardial surface with values of 18 kPa and 12% at the epicardial surface. Embedding an electrically homogeneous cell model for the same simulations produced equivalent values of 36.5 kPa, 4% at the endocardium and 14 kPa, 13.5% at the epicardium. CONCLUSION: The substantial redistribution of fibre lengths during the early pre-ejection phase of systole may play a significant role in preparing the mid-wall fibres to contract. The inclusion of transmural heterogeneity of action potential duration has a marked effect on reducing sarcomere length transmural dispersion during repolarization.
Integration from proteins to organs: the IUPS Physiome Project.
The IUPS Physiome Project is an internationally collaborative open source project intended to provide a public domain framework for computational physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales and across all organ systems. Here, we illustrate the application of this multi-scale modeling approach to three organ systems: the heart, the lungs and the musculo-skeletal system, and in each case we show how the organ level models incorporate tissue and cell-level physiology. Although the computational physiology framework presented here does not yet incorporate models of ageing processes, the model-based approach is certainly capable of describing ageing and disease-related processes both via parameter changes within the models of normal physiological processes and via models of additional processes added to the framework.
A strategy for integrative computational physiology.
Organ function (the heart beat for example) can only be understood through knowledge of molecular and cellular processes within the constraints of structure-function relations at the tissue level. A quantitative modeling framework that can deal with these multiscale issues is described here under the banner of the International Union of Physiological Sciences Physiome Project.
CT-based geometry analysis and finite element models of the human and ovine bronchial tree.
The interpretation of experimental results from functional medical imaging is complicated by intersubject and interspecies differences in airway geometry. The application of computational models in understanding the significance of these differences requires methods for generation of subject-specific geometric models of the bronchial airway tree. In the current study, curvilinear airway centerline and diameter models have been fitted to human and ovine bronchial trees using detailed data segmented from multidetector row X-ray-computed tomography scans. The trees have been extended to model the entire conducting airway system by using a volume-filling algorithm to generate airway centerline locations within detailed volume descriptions of the lungs or lobes. Analysis of the geometry of the scan-based and model-based airways has verified their consistency with measures from previous anatomic studies and has provided new anatomic data for the ovine bronchial tree. With the use of an identical parameter set, the volume-filling algorithm has produced airway trees with branching asymmetry appropriate for the human and ovine lung, demonstrating the dependence of the method on the shape of the lung or lobe volume. The modeling approach that has been developed can be applied to any level of detail of the airway tree and into any volume shape for the lung; hence it can be used directly for different individuals or animals and for any number of scan-based airways. The resulting models are subject-specific computational meshes with anatomically consistent geometry, suitable for application in simulation studies.
Computational physiology and the Physiome Project.
Bioengineering analyses of physiological systems use the computational solution of physical conservation laws on anatomically detailed geometric models to understand the physiological function of intact organs in terms of the properties and behaviour of the cells and tissues within the organ. By linking behaviour in a quantitative, mathematically defined sense across multiple scales of biological organization--from proteins to cells, tissues, organs and organ systems--these methods have the potential to link patient-specific knowledge at the two ends of these spatial scales. A genetic profile linked to cardiac ion channel mutations, for example, can be interpreted in relation to body surface ECG measurements via a mathematical model of the heart and torso, which includes the spatial distribution of cardiac ion channels throughout the myocardium and the individual kinetics for each of the approximately 50 types of ion channel, exchanger or pump known to be present in the heart. Similarly, linking molecular defects such as mutations of chloride ion channels in lung epithelial cells to the integrated function of the intact lung requires models that include the detailed anatomy of the lungs, the physics of air flow, blood flow and gas exchange, together with the large deformation mechanics of breathing. Organizing this large body of knowledge into a coherent framework for modelling requires the development of ontologies, markup languages for encoding models, and web-accessible distributed databases. In this article we review the state of the field at all the relevant levels, and the tools that are being developed to tackle such complexity. Integrative physiology is central to the interpretation of genomic and proteomic data, and is becoming a highly quantitative, computer-intensive discipline.
Giving form to the function of the heart: embedding cellular models in an anatomical framework.
A computational framework is presented for integrating the electrical, mechanical, and biochemical functions of the heart. The construction of efficient finite element representations of canine and porcine ventricular geometry and microstructure is outlined. Computational techniques are applied to solve large deformation soft tissue mechanics by using orthotropic constitutive laws for myocardial tissue and models of active tension generation embedded at the Gauss points in the finite element mesh. The reaction-diffusion equations governing electrical current flow in the heart are solved on a grid of deforming material points that access systems of ordinary differential equations representing the cellular processes underlying the cardiac action potential. Navier-Stokes equations are solved to predict coronary blood flow in a system of branching blood vessels embedded in the deforming myocardium.
Ventricular mechanics in diastole: material parameter sensitivity.
Models of ventricular mechanics have been developed over the last 20 years to include finite deformation theory, anisotropic and inhomogeneous material properties and an accurate representation of ventricular geometry. As computer performance and the computational efficiency of the models improve, clinical application of these heart mechanics models is becoming feasible. One such application is to estimate myocardial material properties by adjusting the constitutive parameters to match wall deformation from MRI or ultrasound measurements, together with a measurement (or estimate) of ventricular pressure. Pigs are now the principal large animal model for these studies and in this paper we present the development of a new three-dimensional finite element model of the heart based on measurements of the geometry and the fibre and sheet orientations of pig hearts. The end-diastolic deformation of the model is computed using the "pole-zero" constitutive law which we have previously used to model the mechanics of passive myocardial tissue specimens. The sensitivities of end-diastolic fibre-sheet material strains and heart shape to changes in the material parameters are computed for the parameters of the pole-zero law in order to assess the utility of the models for inverse material property determination.
A deformable finite element derived finite difference method for cardiac activation problems.
We present a finite element (FE) derived finite difference (FD) technique for solving cardiac activation problems over deforming geometries using a bidomain framework. The geometry of the solution domain is defined by a FE mesh and over these FEs a high resolution FD mesh is generated. The difference points are located at regular intervals in the normalized material space within each of the FEs. The bidomain equations are then transformed to the embedded FD mesh which provides a solution space that is both regular and orthogonal. The solution points move in physical space with any deformation of the solution domain, but the equations are set up in such a way that the solution is invariant as it is constructed in material space. The derivation of this new solution technique is presented along with a series of examples that demonstrate the accuracy of this bidomain framework.
The IUPS human Physiome Project.
The Physiome Project of the International Union of Physiological Sciences (IUPS) is attempting to provide a comprehensive framework for modelling the human body using computational methods which can incorporate the biochemistry, biophysics and anatomy of cells, tissues and organs. A major goal of the project is to use computational modelling to analyse integrative biological function in terms of underlying structure and molecular mechanisms. To support that goal the project is establishing web-accessible physiological databases dealing with model-related data, including bibliographic information, at the cell, tissue, organ and organ system levels. Here we discuss the background and goals of the project, the problems of modelling across multiple spatial and temporal scales, and the development of model ontologies and markup languages at all levels of biological function.