Biomedical subjects

Andrew J Pullan

Publications and source records attributed to Andrew J Pullan.

8 recordsLinked to original sources

PubMed2004

Correction of motion artifact in transmembrane voltage-sensitive fluorescent dye emission in hearts.

Fast voltage-sensitive dyes are widely used to image cardiac electrical activity. Typically, the emission spectrum of these fluorochromes is wavelength shifted with altered membrane potential, but the optical signals obtained also decay with time and are affected by contraction. Ratiometry reduces, but may not fully remove, these artifacts. An alternate approach has been developed in which the time decay in simultaneously acquired short- and long-wavelength signals is characterized nonparametrically and removed. Motion artifact is then identified as the time-varying signal component common to both decay-corrected signals and subtracted. Performance of this subtraction technique was compared with ratiometry for intramural optical signals acquired with a fiber-optic probe in an isolated, Langendorff-perfused pig heart preparation (n = 4) stained with di-4-ANEPPS. Perfusate concentration of 2,3-butanedione monoxime was adjusted (7.5-12.5 mM) to alter contractile activity. Short-wavelength (520-600 nm) and long-wavelength (>600 nm) signals were recorded over 8-16 cardiac cycles at 6 sites across the left ventricular free wall in sinus rhythm and during pacing. A total of 451 such data sets were acquired. Appreciable wall motion was observed in 225 cases, with motion artifact classed as moderate (less than modulation due to action potential) in 187 and substantial (more than modulation due to action potential) in 38. In all cases, subtraction performed as well as, or better than, ratiometry in removing motion artifact and decay. Action potential morphology was recovered more faithfully by subtraction than by ratiometry in 58 of 187 and 31 of 38 cases with moderate and substantial motion artifact, respectively. This novel subtraction approach may therefore provide a means of reducing the concentration of uncoupling agents used in cardiac optical mapping studies.

Action Potentials↗

PubMed2003

Cardiac electrical activity--from heart to body surface and back again.

We report here on our latest developments in the forward and inverse problems of electrocardiology. In the forward problem, a coupled cellular model of cardiac excitation-contraction is embedded within an anatomically realistic model of the cardiac ventricles, which is itself embedded within a torso model. This continuum modelling framework allows the effects of cellular-level activity on the surface electrocardiogram (ECG) to be carefully examined. Furthermore, the contributions of contraction and local ischemia on body surface recordings can also be elucidated. Such information can provide theoretical limits to the sensitivity and ultimately the detection capability of body surface ECG recordings. Despite being very useful, such detailed forward modelling is not directly applicable when seeking to use densely sampled ECG information to assess a patient in a clinical environment (the inverse problem). In such a situation patient specific models must be constructed and, due to the nature of the inverse problem, the level of detail that can be reliably reproduced is limited. Extensive simulation studies have shown that the accuracy with which the heart is localised within the torso is the primary limiting factor. To further identify the practical performance capabilities of the current inverse algorithms, high quality experimental data is urgently needed. We have been working towards such an objective with a number of groups, including our local hospital in Auckland. At that hospital, in patients undergoing catheter ablation surgery, up to 256 simultaneous body surface signals were recorded by using various catheter pacing protocols. The geometric information required to customize the heart and torso model was obtained using a combination of ultrasound and laser scanning technologies. Our initial results indicate that such geometric imaging modalities are sufficient to produce promising inversely-constructed activation profiles.

Algorithms↗

PubMed2003

Altered T wave dynamics in a contracting cardiac model.

INTRODUCTION: The implications of mechanical deformation on calculated body surface potentials are investigated using a coupled biophysically based model. METHODS AND RESULTS: A cellular model of cardiac excitation-contraction is embedded in an anatomically accurate two-dimensional transverse cross-section of the cardiac ventricles and human torso. Waves of activation and contraction are induced by the application of physiologically realistic boundary conditions and solving the bidomain and finite deformation equations. Body surface potentials are calculated from these activation profiles by solving Laplace's equation in the passive surrounding tissues. The effect of cardiac deformation on electrical activity, induced by contraction, is demonstrated in both single-cell and tissue models. Action potential duration is reduced by 7 msec when the single cell model is subjected to a 10% contraction ramp applied over 400 msec. In the coupled electromechanical tissue model, the T wave of the ECG is shown to occur 18 msec earlier compared to an uncoupled excitation model. To assess the relative effects of myocardial deformation on the ECG, the activation sequence and tissue deformation are separated. The coupled and uncoupled activation sequences are mapped onto the undeforming and deforming meshes, respectively. ECGs are calculated for both mappings. CONCLUSION: Adding mechanical contraction to a mathematical model of the heart has been shown to shift the T wave on the ECG to the left. Although deformation of the myocardium resulting from contraction reduces the T wave amplitude, cell stretch producing altered cell membrane kinetics is the major component of this temporal shift.

Action Potentials↗

PubMed2003

Effects of experimental and modeling errors on electrocardiographic inverse formulations.

The inverse problem of electrocardiology aims to reconstruct the electrical activity occurring within the heart using information obtained noninvasively on the body surface. Potentials obtained on the torso surface can be used as input for the inverse problem and an electrical image of the heart obtained. There are a number of different inverse algorithms currently used to produce electrical images of the heart. The relative performances of these inverse algorithms at this stage is largely unknown. Although there have been many simulation studies investigating the accuracy of each of these algorithms, to date, there has been no comprehensive study which compares a wide variety of inverse methods. By performing a detailed simulation study, we compare the performances of epicardial potential [Tikhonov, Truncated singular value decomposition (TSVD), and Greensite] and myocardial activation-based (critical point) inverse simulations along with different methods of choosing the appropriate level of regularization (optimal, L-curve, composite residual and smoothing operator, zero-crossing) to apply to each of these inverse methods. We also examine the effects of a variety of signal error, material property error, geometric error and a combination of these errors on each of the electrocardiographic inverse algorithms. Results from the simulation study show that the activation-based method is able to produce solutions which are more accurate and stable than potential-based methods especially in the presence of correlated errors such as geometric uncertainty. In general, the Greensite-Tikhonov method produced the most realistic potential-based solutions while the zero-crossing and L-curve were the preferred method for determining the regularization parameter. The presence of signal or material property error has little effect on the inverse solutions when compared with the large errors which resulted from the presence of any geometric error. In the presence of combined Gaussian and correlated errors representing conditions which may be encountered in an experimental or clinical environment, there was less variability between potential-based solutions produced by each of the inverse algorithms.

Algorithms↗

PubMed2003

Comparison of potential- and activation-based formulations for the inverse problem of electrocardiology.

Two predominant source formulations for the inverse problem of electrocardiology currently exist. They involve the reconstruction of epicardial potentials or myocardial activation times from noninvasively recorded torso surface potentials. Each of these formulations have their advantages, however, they have not been systematically compared against each other. We present results from a simulation study which compared a number of epicardial potential (Tikhonov, Truncated singular value decomposition (TSVD), Greensite-Tikhonov and Greensite-TSVD), and a myocardial activation time formulation for the inverse problem of electrocardiology. A number of different methods were also used to determine the appropriate level of regularization (optimal, L-curve, zero-crossing, and composite residual and smoothing operator) to apply to each formulation. The simulation study was conducted using an anatomically based boundary element porcine model with a variety of cardiac sources. Varying levels of geometric error were introduced to the system and solutions were computed using each of the inverse algorithms. Results show that under pure Gaussian noise potential-based methods performed best at low noise levels while the activation-based method was less effected by higher noise levels. In the presence of correlated geometric error, the activation-based method out performed the potential methods, with the Greensite-Tikhonov method being the most favored potential-based method when using the L-curve or zero-crossing method to determine the regularization parameter.

Algorithms↗

PubMed2003

The effect of torso impedance on epicardial and body surface potentials: a modeling study.

Experimental results have been published that report marked changes in measured epicardial potentials when the conductivity of the material surrounding the heart is altered. These reports raise a question as to the validity of the traditional two step, equivalent cardiac source approach to modeling the forward problem of electrocardiology as the equivalent source calculation occurs in what is effectively an isolated cardiac region. In the physical situation the heart is surrounded by a torso that contains many different tissue types with different conductivities and is certainly not isolated. Here, a fully coupled model of the problem is employed where the electrical pathways are continuous from a cellular level through to the body surface. This model is used to investigate the effects that torso inhomogeneities have on epicardial and body surface potentials, including comparisons with a traditional two step approach. In particular, it is shown that adding lungs changes the epicardial potentials by 17%, which is consistent with the reported experimental results. In none of the tested situations did the equivalent source approach completely reproduce the fully coupled results, supporting the notion that a fully coupled approach is required to properly solve the forward problem of electrocardiology.

Abdomen↗

PubMed2003

Modeling total heart function.

Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.

Animals↗

PubMed2002

Cardiac microstructure: implications for electrical propagation and defibrillation in the heart.

Our understanding of the electrophysiological properties of the heart is incomplete. We have investigated two issues that are fundamental to advancing that understanding. First, there has been widespread debate over the mechanisms by which an externally applied shock can influence a sufficient volume of heart tissue to terminate cardiac fibrillation. Second, it has been uncertain whether cardiac tissue should be viewed as an electrically orthotropic structure, or whether its electrical properties are, in fact, isotropic in the plane orthogonal to myofiber direction. In the present study, a computer model that incorporates a detailed three-dimensional representation of cardiac muscular architecture is used to investigate these issues. We describe a bidomain model of electrical propagation solved in a discontinuous domain that accurately represents the microstructure of a transmural block of rat left ventricle. From analysis of the model results, we conclude that (1) the laminar organization of myocytes determines unique electrical properties in three microstructurally defined directions at any point in the ventricular wall of the heart, and (2) interlaminar clefts between layers of cardiomyocytes provide a substrate for bulk activation of the ventricles during defibrillation.

Animals↗