Biomedical subjects

P J Hunter

Publications and source records attributed to P J Hunter.

At least 19 recordsLinked to original sources

PubMed2006

Myocardial material parameter estimation-a comparative study for simple shear.

The study of ventricular mechanics-analyzing the distribution of strain and stress in myocardium throughout the cardiac cycle-is crucially dependent on the accuracy of the constitutive law chosen to represent the highly nonlinear and anisotropic properties of passive cardiac muscle. A number of such laws have been proposed and fitted to experimental measurements of stress-strain behavior. Here we examine five of these laws and compare them on the basis of (i) "goodness of fit:" How well they fit a set of six shear deformation tests, (ii) "determinability:" How well determined the objective function is at the optimal parameter fit, and (iii) "variability:" How well determined the material parameters are over the range of experiments. These criteria are utilized to discuss the advantages and disadvantages of the constitutive laws.

Animals↗

PubMed2005

A quantitative analysis of cardiac myocyte relaxation: a simulation study.

The determinants of relaxation in cardiac muscle are poorly understood, yet compromised relaxation accompanies various pathologies and impaired pump function. In this study, we develop a model of active contraction to elucidate the relative importance of the [Ca2+]i transient magnitude, the unbinding of Ca2+ from troponin C (TnC), and the length-dependence of tension and Ca2+ sensitivity on relaxation. Using the framework proposed by one of our researchers, we extensively reviewed experimental literature, to quantitatively characterize the binding of Ca2+ to TnC, the kinetics of tropomyosin, the availability of binding sites, and the kinetics of crossbridge binding after perturbations in sarcomere length. Model parameters were determined from multiple experimental results and modalities (skinned and intact preparations) and model results were validated against data from length step, caged Ca2+, isometric twitches, and the half-time to relaxation with increasing sarcomere length experiments. A factorial analysis found that the [Ca2+]i transient and the unbinding of Ca2+ from TnC were the primary determinants of relaxation, with a fivefold greater effect than that of length-dependent maximum tension and twice the effect of tension-dependent binding of Ca2+ to TnC and length-dependent Ca2+ sensitivity. The affects of the [Ca2+]i transient and the unbinding rate of Ca2+ from TnC were tightly coupled with the effect of increasing either factor, depending on the reference [Ca2+]i transient and unbinding rate.

Animals↗

PubMed2005

An anatomically based patient-specific finite element model of patella articulation: towards a diagnostic tool.

A 3D anatomically based patient-specific finite element (FE) model of patello-femoral (PF) articulation is presented to analyse the main features of patella biomechanics, namely, patella tracking (kinematics), quadriceps extensor forces, surface contact and internal patella stresses. The generic geometries are a subset from the model database of the International Union of Physiological Sciences (IUPS) (http://www.physiome.org.nz) Physiome Project with soft tissue derived from the widely used visible human dataset, and the bones digitised from an anatomically accurate physical model with muscle attachment information. The models are customised to patient magnetic resonance images using a variant of free-form deformation, called 'host-mesh' fitting. The continuum was solved using the governing equation of finite elasticity, with the multibody problem coupled through contact mechanics. Additional constraints such as tissue incompressibility are also imposed. Passive material properties are taken from the literature and implemented for deformable tissue with a non-linear micro-structurally based constitutive law. Bone and cartilage are implemented using a 'St-Venant Kirchoff' model suitable for rigid body rotations. The surface fibre directions have been estimated from anatomy images of cadaver muscle dissections and active muscle contraction was based on a steady-state calcium-tension relation. The 3D continuum model of muscle, tendon and bone is compared with experimental results from the literature, and surgical simulations performed to illustrate its clinical assessment capabilities (a Maquet procedure for reducing patella stresses and a vastus lateralis release for a bipartite patella). Finally, the model limitations, issues and future improvements are discussed.

Computer Simulation↗

PubMed2005

The Noble cardiac ventricular electrophysiology models in CellML.

We present a review of the cardiac ventricular cell electrophysiology models developed by Prof. Denis Noble and colleagues as an example of how models may be published using a web-based CellML publication framework. The models reviewed have been marked-up in CellML and then used to compute all results presented here. The models are freely available from a website as are the specific numerical experiments discussed in this review and the tools used to perform the simulations.

Animals↗

PubMed2005

A cerebral palsy assessment tool using anatomically based geometries and free-form deformation.

A geometrical analysis tool for investigating muscle length change in cerebral palsy (CP) patients is presented. A subset of anatomically based geometries from the International Union of Physiological Sciences (IUPS) Physiome Project is used, which is derived from the visible human (VH) data set with muscle attachment information, and customised using volume-preserving free-form deformation (FFD), the 'host-mesh' technique. The model's intended use is to provide pre- and post-surgery assessment for muscle lengthening, a surgery performed to help slacken tight muscles and improve gait. The model is illustrated using healthy patient data from motion capture as a validation followed by three CP case studies to highlight its use. The methodology is presented in three stages, (1) a FFD of the complete lower limb, (2) a focused geometric study on the semimembranosus (SM) and gastrocnemius (GT) muscles, and (3) an improved hybrid mechanics-FFD approach as an improvement for future analysis, with differentiation between muscle and tendon lengthening, and contact detection between sliding muscles. Finally, the issues, limitations, in particular with the marker system, and model improvements are discussed.

Cerebral Palsy↗

PubMed2005

Modelling the passive and nerve activated response of the rectus femoris muscle to a flexion loading: a finite element framework.

A muscle modelling framework is presented which relates the mechanical response of the rectus femoris muscle (at the organ level) to tissue level properties, with the capability of linking to the cellular level as part of the IUPS Physiome Project. This paper will outline our current approach to muscle modelling incorporating micro-structural passive and active properties including fibre orientations and nerve innervation. The technique is based on finite deformation (using FE analysis) coupled to electrical nerve initiated muscle activation, and we present the influence of active tension through an eccentric contraction at specific flexion angles. Finally we discuss the future goals of incorporating cell mechanics and validating at the organ level to provide a complete diagnostic tool with the ability to relate mechanisms of failure across spatial scales.

Action Potentials↗

PubMed2005

Anatomically based modelling of the human skull and jaw.

We present here an anatomically based model of the human masticatory system that provides a framework for simulating the complex chewing process. The initial motivation for creating this model was the desire to have a computational model of the human jaw that can be used to simulate the action of simple bites, and to calculate the stresses and forces on the teeth that are involved. The model created also provides a platform that can be used to investigate other features of the masticatory system. To construct this global model, individual models of the bones of the skull and jaw were created from generic data sets. Geometric models of the muscles of mastication were also created and attached to the appropriate bones. To complete this initial model, representations of the crowns of the teeth were created and a basic model of the temporomandibular joint (TMJ) was included. The finite element method was used to solve for the stresses and strains created by the loading conditions during a clenching simulation involving the mandible bone. The model presented here is also discussed in relation to a model of the entire musculo-skeletal system being developed as part of the Physiome Project.

Computer Simulation↗

PubMed2003

Anatomically based geometric modelling of the musculo-skeletal system and other organs.

Anatomically based finite element geometries are becoming increasingly popular in physiological modelling, owing to the demand for modelling that links organ function to spatially distributed properties at the protein, cell and tissue level. We present a collection of anatomically based finite element geometries of the musculo-skeletal system and other organs suitable for use in continuum analysis. These meshes are derived from the widely used Visible Human (VH) dataset and constitute a contribution to the world wide International Union of Physiological Sciences (IUPS) Physiome Project (www.physiome.org.nz). The method of mesh generation and fitting of tricubic Hermite volume meshes to a given dataset is illustrated using a least-squares algorithm that is modified with smoothing (Sobolev) constraints via the penalty method to account for sparse and scattered data. A technique ("host mesh" fitting) based on "free-form" deformation (FFD) is used to customise the fitted (generic) geometry. Lung lobes, the rectus femoris muscle and the lower limb bones are used as examples to illustrate these methods. Geometries of the lower limb, knee joint, forearm and neck are also presented. Finally, the issues and limitations of the methods are discussed.

Algorithms↗

PubMed2003

Genetic mapping of the novel Turnip mosaic virus resistance gene TuRB03 in Brassica napus.

A new source of resistance to the pathotype 4 isolate of Turnip mosaic virus (TuMV) CDN 1 has been identified in Brassica napus (oilseed rape). Analysis of segregation of resistance to TuMV isolate CDN 1 in a backcross generation following a cross between a resistant and a susceptible B. napus line showed that the resistance was dominant and monogenic. Molecular markers linked to this dominant resistance were identified using amplified fragment length polymorphism (AFLP) and microsatellite bulk segregant analysis. Bulks consisted of individuals from a BC(1) population with the resistant or the susceptible phenotype following challenge with CDN 1. One AFLP and six microsatellite markers were associated with the resistance locus, named TuRB03, and these mapped to the same region on chromosome N6 as a previously mapped TuMV resistance gene TuRB01. Further testing of TuRB03 with other TuMV isolates showed that it was not effective against all pathotype 4 isolates. It was effective against some, but not all pathotype 3 isolates tested. It provided further resolution of TuMV pathotypes by sub-dividing pathotypes 3 and 4. TuRB03 also provides a new source of resistance for combining with other resistances in our attempts to generate durable resistance to this virus.

Brassica napus↗

PubMed2003

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

Database Management Systems↗

PubMed2002

Strain measurement in biaxially loaded inhomogeneous, anisotropic elastic membranes.

This paper considers the problem of measuring the strain field in biaxially loaded elastic membranes, such as soft biological tissue. Cross-correlation of intrinsic or applied speckle patterns were used to calculate the 2D displacements of small regions on the surface of a deforming membrane. This method was able to resolve 2D displacements to within a twentieth of a pixel. A finite-element model with bicubic-Hermite interpolation was used to represent the geometry of the membrane in the undeformed state. This model was fitted to the measured displacements to obtain the geometry of the membrane in the deformed state, and the strain field was calculated from the change in geometry. The strain fields were measured in both an inhomogeneous isotropic rubber membrane and a section of sheep diaphragm.

Algorithms↗

PubMed2002

Instrumentation and procedures for estimating the constitutive parameters of inhomogeneous elastic membranes.

This study presents a method for estimating the spatial variations in material properties of elastic membranes, such as biological tissue, which contain both inhomogeneous strain fields and inhomogeneous material properties. In order to validate the method, an inhomogeneous, isotropic rubber membrane was biaxially loaded to obtain a set of states. A neo-Hookean finite element model, together with the measured strains, was used to estimate the material parameters by minimizing the residuals between the measured and modelled residual on surface tractions.

Anisotropy↗

PubMed2002

The IUPS Physiome Project. International Union of Physiological Sciences.

Modern medicine is currently benefiting from the development of new genomic and proteomic techniques, and also from the development of ever more sophisticated clinical imaging devices. This will mean that the clinical assessment of a patient's medical condition could, in the near future, include information from both diagnostic imaging and DNA profile or protein expression data. 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. This paper discusses the development of comprehensive integrative mathematical models of human physiology based on patient-specific quantitative descriptions of anatomical structures and models of biophysical processes which reach down to the genetic level.

Biophysics↗

PubMed2001

Characterising respiratory airway gas mixing using a lumped parameter model of the pulmonary acinus.

A lumped parameter model of a human pulmonary acinus is derived using results from gas mixing simulations in an anatomically-based asymmetric multi-branching model of the acinus coupled to a symmetric conducting airway model. The model respiratory airways change length in proportion to the cube root of their volume change, and the diameters are updated accordingly assuming constant duct cross-sectional area. The lumped parameter model applies a flux boundary condition at the end of a transitional bronchiole during inspiration to enable realistic concentration changes at this position; during expiration inspiratory parameters are used to predict concentrations at the end of the associated transitional bronchiole. The predicted concentrations are used as time-varying fixed boundary conditions at the end of the transitional bronchiole in conducting airway models during expiration. The current lumped parameter model is most accurate for tidal volumes between 500 and 1500 ml, and equal inspiration and expiration durations of 2 sec. The model's accuracy decreases for changes in breath duration.

Bronchi↗

PubMed2001

Multibreath washout analysis: modelling the influence of conducting airway asymmetry.

The contributions of respiratory and conducting airway asymmetry, gas exchange, and non-uniform ventilation to the sloping alveolar plateau in phase III of the gas washout curve are investigated using mathematical models of the human lung. The models range from fully symmetric, to a detailed asymmetric conducting airway model coupled with 29445 lumped parameter respiratory airway models. A gas transport equation is solved in the models using a Lagrange-Galerkin method. The alveolar slope is normalised by the mean expired gas concentration to give S(n). The model results confirm that first breath S(n) is influenced mainly by respiratory airway asymmetry, and that at near-normal levels of ventilation the conducting airway asymmetry contributes a significant amount to further increases in S(n). Gas exchange moderates the plot of S(n) against breath number, such that it approaches a plateau in later breaths. Non-uniform flow also alters S(n), indicating that an accurate description of the pleural pressure gradient will be necessary for more accurate simulations.

Computer Simulation↗

PubMed2000

The effect of synthetic patch repair of coarctation on regional deformation of the aortic wall.

BACKGROUND: A long-term complication of synthetic patch repair of coarctation is true aneurysm formation. AIM: An in vitro study was undertaken to determine the effects of patch angioplasty on aortic geometry and strain adjacent to the patch. METHODS: Segments of human descending thoracic aorta were subject to 10 pressure loading cycles (10-120 mm Hg; 1.36-16.32 kPa) before and after simulated coarctation repair with a synthetic patch. Local curvature and strain were estimated by fitting a geometric model to reconstructed three-dimensional surface marker points. RESULTS: In the control aortas, when pressure increased from 11 +/- 1.0 to 124 +/- 4.0 mm Hg (1.5 +/- 0.14 to 16.86 +/- 0.54 kPa), average circumferential curvature decreased from 0.1543 +/- 0.03 to 0.1065 +/- 0.03 mm(-1). The average major extension reached a maximum of 1.43 +/- 0.08. After patch implantation, the average circumferential curvature was reduced relative to control at all pressures. Average major extensions were significantly greater than paired control values and reached a maximum of 1.55 +/- 0.08 at 122 +/- 4.0 mm Hg (16.59 +/- 0. 54 kPa). Substantial strain inhomogeneity was observed and major extensions were greatest immediately adjacent to the patch. INFERENCE: Synthetic patch repair of coarctation of the aorta increases wall strain and produces significant regional gradients in strain. With control aortic material properties there may be a substantial increase in wall stress immediately adjacent to the aorta, which could lead to true aneurysm formation.

Adolescent↗

PubMed2000

Generation of an anatomically based three-dimensional model of the conducting airways.

An anatomically accurate model of the conducting airways is essential for adequately simulating gas mixing, particle deposition, heat and water transfer, and fluid distribution. We have extended a two-dimensional tree-growing algorithm to three dimensions for generation of a host-shape dependent three-dimensional conducting airway model. Terminal branches in the model are both length limited and volume-supplied limited. A limit is imposed on the maximum possible branch angle between a daughter and parent branch. Comparison of the resulting model with morphometric data shows that the algorithm produces branching and length ratios, path lengths, numbers of branches, and branching angles very close to those from the experimental data. The correlation between statistics from the generated model and those from morphometric studies suggests that the conducting airway structure can be described adequately using a "supply and demand" algorithm. The resulting model is a computational mesh that can be used for simulating transport phenomena.

Algorithms↗

PubMed2000

Effects of material properties and geometry on electrocardiographic forward simulations.

This paper investigates the effect on torso potentials of changes in the material properties of the torso volume conductor and changes in the relative geometry of the heart and torso. The investigations are performed using a number of forward simulations with a high-order coupled finite element/boundary element torso model. This torso model contains descriptions of the epicardium, lungs, skeletal muscle (with a continuously varying fiber field) and subcutaneous fat. The number of nodes, elements and solution degrees-of-freedom used in the computational torso model are considerably smaller than previous torso models of similar complexity. The successful forward simulations in this paper hence demonstrate the use of the high-order coupled approach with realistic problems. The results of the torso simulations show that the torso inhomogeneities do affect the torso potentials but do not affect the distribution or pattern of the torso potentials. The inhomogeneities considered are found to have a varying, but important, effect on the torso potentials. The effect of the subcutaneous fat is found to be more important and the effect of the skeletal muscle is found to be less important than previous reports in the literature. The results also show that the relative geometry of the heart and torso is very important in determining the torso potential magnitudes and distributions.

Abdomen↗