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Cardiac electrophysiology and tissue structure: bridging the scale gap with a joint measurement and modelling paradigm.

Significant tissue structures exist in cardiac ventricular tissue that are of supracellular dimension. It is hypothesized that these tissue structures contribute to the discontinuous spread of electrical activation, may contribute to arrhymogenesis and also provide a substrate for effective cardioversion. However, the influences of these mesoscale tissue structures in intact ventricular tissue are difficult to understand solely on the basis of experimental measurement. Current measurement technology is able to record at both the macroscale tissue level and the microscale cellular or subcellular level, but to date it has not been possible to obtain large volume, direct measurements at the mesoscales. To bridge this scale gap in experimental measurements, we use tissue-specific structure and mathematical modelling. Our models have enabled us to consider key hypotheses regarding discontinuous activation. We also consider the future developments of our intact tissue experimental programme.

Action Potentials↗

Prediction of muscle recruitment and its effect on joint reaction forces during knee exercises.

This study examined the hypothesis that muscle recruitment of the tibiofemoral joint and joint reaction forces during isometric and isokinetic exercises depends on the existing degrees of freedom of the knee and the direction and type of external load applied during exercise. When three-dimensional knee joint rotation was considered (three degrees of freedom), antagonistic muscle activities were predicted using an inverse dynamic problem formulation and muscle modeling optimization procedures. The results showed that the antagonistic activities of flexors during knee flexion/extension exercise increased the joint compressive forces and decreased the anterior tibial shear forces. Comparison of different knee joint modeling assumptions indicated that modeling a single degree of freedom in flexion/extension for the knee will underestimate the antagonistic muscle function.

Biomechanical Phenomena↗

Lead-field bases for electroencephalography source imaging.

In recent years, significant progress has been made in the area of electroencephalography (EEG) source imaging. Source localization on simple spherical models has become increasingly efficient, with consistently reported accuracy of within 5 mm. In contrast, source localization on realistic head models remains slow, with subcentimeter accuracy being the exception rather than the norm. A primary reason for this discrepancy is that most source imaging techniques are based on lead fields. While the lead field for simplified geometries can be easily computed analytically, an efficient method for computing realistic domain lead fields has, until now, remained elusive. In this paper, we propose two efficient methods for computing realistic EEG lead-field bases: the first is element oriented and the second is node oriented. We compare these two bases, discuss how they can be used to apply recent source imaging methods to realistic models, and report timings for constructing the bases.

Biomedical Engineering↗

Validation of rapid velocity encoded cine imaging of a dynamically complex flow field using turbo block regional interpolation scheme for k space.

Block regional interpolation scheme for k space (BRISK) is a sparse sampling approach to allow rapid magnetic resonance imaging of dynamic events. Rapid velocity encoded cine (VEC) imaging with Turbo BRISK is potentially an important clinical diagnostic technique for cardiovascular diseases. Previously we applied BRISK and Turbo BRISK to imaging pulsatile flow in a straight tube. To evaluate the capabilities of Turbo BRISK imaging in more complex dynamic flow fields such as might exist in the human vasculature, an in vitro curved tube model, similar in geometry to the aortic arch, was fabricated and imaged under pulsatile flow conditions. Velocity maps were obtained using conventional VEC and Turbo BRISK (turbo factors 1 through 5). Comparison of the flow fields obtained with each higher order turbo factor showed excellent agreement with conventional VEC with minimal loss of information. Similarly, flow maps showed good agreement with the profiles from a laser Doppler velocimetry model. Turbo-5 BRISK, for example, allowed a 94% savings in imaging time, reducing the conventional imaging time from over 8 min to a near breath-hold imaging period of 31 s. Turbo BRISK shows excellent promise toward the development of a clinical tool to evaluate complex dynamic intravascular flow fields.

Biomedical Engineering↗

Spatial filter approach for comparison of the forward and inverse problems of electroencephalography and magnetoencephalography.

We present an analysis of the relative information content of cortical current source reconstructions from electroencephalogram (EEG) and magnetoencephalogram (MEG) forward calculations by examining the spatial filters that relate the internal sources with the externally measured electric potentials and magnetic fields. The forward spatial filters are seen to be low-pass functions of spatial frequency and spatial resolution degrades in external measurements. Inverse spatial filters may be used to reconstruct cortical sources from external data, but since they are high-pass functions of spatial frequency, they must be regularized to avoid instabilities caused by noise at higher spatial frequencies. The regularization process limits the spatial resolution of source reconstructions. EEG forward spatial filters fall off at lower spatial frequencies than MEG filters; hence, there is less information available in higher spatial frequencies resulting in lower spatial resolution in inverse reconstructions. The tangential component of the magnetic field provides even higher spatial resolution than can be obtained using the radial component. An accompanying article examines the surface Laplacian for both the EEG and the MEG.

Electric Conductivity↗

Mechanoelectric feedback in a model of the passively inflated left ventricle.

Mechanoelectric feedback has been described in isolated cells and intact ventricular myocardium, but the mechanical stimulus that governs mechanosensitive channel activity in intact tissue is unknown. To study the interaction of myocardial mechanics and electrophysiology in multiple dimensions, we used a finite element model of the rabbit ventricles to simulate electrical propagation through passively loaded myocardium. Electrical propagation was simulated using the collocation-Galerkin finite element method. A stretch-dependent current was added in parallel to the ionic currents in the Beeler-Reuter ventricular action potential model. We investigated different mechanical coupling parameters to simulate stretch-dependent conductance modulated by either fiber strain, cross-fiber strain, or a combination of the two. In response to pressure loading, the conductance model governed by fiber strain alone reproduced the epicardial decrease in action potential amplitude as observed in experimental preparations of the passively loaded rabbit heart. The model governed by only cross-fiber strain reproduced the transmural gradient in action potential amplitude as observed in working canine heart experiments, but failed to predict a sufficient decrease in amplitude at the epicardium. Only the model governed by both fiber and cross-fiber strain reproduced the epicardial and transmural changes in action potential amplitude similar to experimental observations. In addition, dispersion of action potential duration nearly doubled with the same model. These results suggest that changes in action potential characteristics may be due not only to length changes along the long axis direction of the myofiber, but also due to deformation in the plane transverse to the fiber axis. The model provides a framework for investigating how cellular biophysics affect the function of the intact ventricles.

Action Potentials↗

Effect of a flow-streamlining implant at the distal anastomosis of a coronary artery bypass graft.

Intimal thickening in the coronary artery bypass graft (CABG) distal anastomosis has been implicated as the major cause of restenosis and long-term graft failure. Several studies point to the interplay between nonuniform hemodynamics including disturbed flows and recirculation zones, wall shear stress, and long particle residence time as possible etiologies. The hemodynamic features of two anatomic models of saphenous-vein CABGs were studied and compared. One simulated an anastomosis with both diameter and compliance mismatch and a curvature at the connection, analogous to the geometry observed in a conventional cardiothoracic procedure. The other, simulated an anastomosis with a flow stabilizing anastomotic implant connector which improves current cardiothoracic procedures by eliminating the distal vein bulging and curvature. Physiologic flow conditions were imposed on both models and qualitative analysis of the flow was performed with dye injection and a digital camera. Quantitative analysis was performed with laser Doppler velocimetry. Results showed that the presence of the bulge at the veno-arterial junction, contributed to the formation of accentuated secondary structures (helices), which progress into the flow divider and significantly affect radial velocity components at the host vessel up to four diameters downstream of the junction. The model with the implant, achieved more hemodynamically efficient conditions on the host vessel with higher mean and maximum axial velocities and lower radial velocities than the conventional model. The presence of the sinus may also affect the magnitude and shape of the shear stress at locations where intimal thickening occurs. Thus, the presence of the implant creates a more streamlined environment with more primary and less secondary flow components which may then inhibit the development of intimal thickening, restenosis, and ultimate failure of the saphenous vein graft.

Arteriovenous Anastomosis↗

Induced current impedance technique for monitoring brain cryosurgery in a two-dimensional model of the head.

A fast and robust finite volume solver of the two-dimensional induced current electrical impedance forward problem was developed. The numerical solver was validated by comparison with an existing analytical solution for a symmetrical geometry case, showing an accuracy of 0.07%. The solver was used to theoretically examine the sensitivity of the induced current impedance technique for the medical procedure of monitoring brain cryosurgery. The simulation was performed using a two-dimensional approximation of otherwise realistic geometry model of the head with different ice-ball sizes, simulating the expansion of the frozen lesion. The sensitivity of the scalp potential to the ice-ball size was found to be 53 x 10(-4) (relative scalp potential mm(-2)).

Biomedical Engineering↗

Voronoi polyhedra analysis of optimized arterial tree models.

Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number Nf of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter alpha of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and alpha are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001). The distributions of Nf, V, and S of the CCO models are reasonably well approximated by two-parameter gamma distributions. We study scaling of intravascular blood volume and arterial cross-sectional area with the volume of supplied tissue, the latter being represented by the VP of the respective terminal segments. We observe scaling exponents from 1.20 +/- 0.007 to 1.08 +/- 0.005 for intravascular blood volume and 0.77 +/- 0.01 for arterial cross-sectional area. Setting terminal flows proportional to the associated VP volumes during tree construction yields a relative dispersion of terminal flows of 37% and a coefficient of skewness of 1.12.

Algorithms↗

Accuracy of computational hemodynamics in complex arterial geometries reconstructed from magnetic resonance imaging.

PURPOSE: Combining computational blood flow modeling with three-dimensional medical imaging provides a new approach for studying links between hemodynamic factors and arterial disease. Although this provides patient-specific hemodynamic information, it is subject to several potential errors. This study quantifies some of these errors and identifies optimal reconstruction methodologies. METHODS: A carotid artery bifurcation phantom of known geometry was imaged using a commercial magnetic resonance (MR) imager. Three-dimensional models were reconstructed from the images using several reconstruction techniques, and steady and unsteady blood flow simulations were performed. The carotid bifurcation from a healthy, human volunteer was then imaged in vivo, and geometric models were reconstructed. RESULTS: Reconstructed models of the phantom showed good agreement with the gold standard geometry, with a mean error of approximately 15% between the computed wall shear stress fields. Reconstructed models of the in vivo carotid bifurcation were unacceptably noisy, unless lumenal profile smoothing and approximating surface splines were used. CONCLUSIONS: All reconstruction methods gave acceptable results for the phantom model, but in vivo models appear to require smoothing. If proper attention is paid to smoothing and geometric fidelity issues, models reconstructed from MR images appear to be suitable for use in computational studies of in vivo hemodynamics.

Carotid Arteries↗

Three-dimensional human head finite-element model validation against two experimental impacts.

The impact response of a three-dimensional human head model has been determined by simulating two cadaver tests. The objective of this study was to validate a finite-element human head model under different impact conditions by considering intracranial compressibility. The current University Louis Pasteur model was subjected initially to a direct head impact, of short (6 ms) duration, and the simulation results were compared with published experimental cadaver tests. The model response closely matched the experimental data. A long duration pulse was chosen for the second impact and this necessitated careful consideration of the head-neck joint in order to replicate the experimental kinematics. The skull was defined as a rigid body and was subjected to six velocities. Output from the model did not accurately match the experimental results and this clearly indicates that it is important to validate a finite-element head model under various impact conditions to define the range of validity. Lack of agreement for the second impact is attributed to the nonlinearity in the dynamic behavior of intracranial stress, a problem that is not reported in the literature.

Acceleration↗

Direct inference of the spectra of pericardial potentials using the boundary-element method.

New methods, based on Tikhonov regularization, were developed to infer the magnitude and phase of pericardial potentials directly. These methods were tested in an adult-male torso model using measured human epicardial potentials. With 1% noise added to body-surface potentials, regularization with an optimal parameter at each frequency from 1 to 100 Hz gave an average relative error (RE) in inferred spectral magnitudes of 0.44. Regularization with the composite-residual-smoothing-operator (CRESO) parameter increased the RE slightly to 0.47. With 10% additive noise, 10 mm overestimation of heart radius, and a 10 mm error in heart position, the average CRESO parameter from 1 to 100 Hz gave an average RE of 0.71. Performance was frequency dependent. The smallest REs occurred at low frequencies. With 1% noise, optimal regularization gave average REs of 0.20, 0.40, and 0.53 in the 1-15, 15-46, and 46-100 Hz bands, respectively. Direct inference of spectral magnitudes was more accurate than Fourier transformation of inferred time-domain waveforms. Results suggest that when heart size and location are not known, minimum REs in spectral estimates are found using an overestimated heart size and a regularization parameter which is the average value over the frequency band of interest.

Body Surface Potential Mapping↗

Numerical simulation of oxygen mass transfer in a compliant curved tube model of a coronary artery.

Arterial wall transport of blood-borne oxygen is essential for superficial arterial wall metabolism. The unique geometry and hemodynamics of coronary arteries curved over the heart surface may alter the O2 transport pattern and lead to abnormalities of O2 tension at the inner wall (epicardial surface) which may contribute to atherogenesis. This study focused on O2 transport in a compliant model of a curved coronary artery. A three-dimensional finite element model with moving boundaries was setup to simulate physiological flow and O2 transport in coronary arteries. The full Navier-Stokes equations and the coupled conservation of species equation were solved simultaneously for typical coronary flow characteristics (aspect ratio=10, diameter variation=6%, mean Reynolds number= 150, unsteadiness parameter=3, Schmidt number=2,700). The results indicate a large difference in O2 wall flux (Sherwood number [Sh]) between the outside (Sh about 55) and inside (Sh about 2) walls and imply that O2 transport at the inner wall could be limited by the fluid phase.

Animals↗

Staged growth of optimized arterial model trees.

There is a marked difference in the structure of the arterial tree between epi- and endocardial layers of the human heart. To model these structural variations, we developed an extension to the computational method of constrained constructive optimization (CCO). Within the framework of CCO, a model tree is represented as a dichotomously branching network of straight cylindrical tubes, with flow conditions governed by Poiseuille's law. The tree is grown by successively adding new terminal segments from randomly selected points within the perfusion volume while optimizing the geometric location and topological site of each new connection with respect to minimum intravascular volume. The proposed method of "staged growth" guides the generation of new terminal sites by means of an additional time-dependent boundary condition, thereby inducing a sequence of domains of vascular growth within the given perfusion volume. Model trees generated in this way are very similar to reality in their visual appearance and predict diameter ratios of parent and daughter segments, the distribution of symmetry, the transmural distribution of flow, the volume of large arteries, as well as the ratio of small arterial volume in subendocardial and subepicardial layers in good agreement with experimental data. From this study we conclude that the method of CCO combined with staged growth reproduces many characteristics of the different arterial branching patterns in the subendocardium and the subepicardium, which could not be obtained by applying the principle of minimum volume alone.

Algorithms↗

An admissible solution approach to inverse electrocardiography.

The goal of the inverse problem of electrocardiography is noninvasive discrimination and characterization of normal/abnormal cardiac electrical activity from measurements of body surface potentials. Smoothing and attenuation in the torso volume conductor cause the problem to be ill posed. Standard regularized solutions employ an a priori constraint to achieve reliability and may be biased by the constraint chosen as well as the regularization parameter used to weight it. In this paper, we describe an approach that reformulates this inverse problem as the search for a solution that is a member of an admissible solution set; admissibility is defined in terms of the available constraints. In principle, this approach can utilize as many constraints as may be available, unlike standard techniques which do not easily permit the use of multiple constraints. No regularization parameter is required; instead, we need to choose the nature and size of the constraint sets. Constraints described include several spatial constraints, weighted constraints, and temporal constraints. We describe a solution approach based on iterative convex optimization, and the algorithm--the ellipsoid algorithm--which we have used. Accuracy and feasibility of the method are illustrated with simulation results using dipole sources and measured epicardial potentials.

Algorithms↗

Influence of vasoactive drugs on wall shear stress distribution in the abdominal aortic bifurcation: an in vitro study.

The present study compares the wall shear stress (rate) distribution in a compliant aortic bifurcation model under three different hemodynamic states: normal state, angiotensin II infusion state (vasoconstrictor), and isoproterenol infusion state (vasodilator). Using a Newtonian blood analog fluid, flow wave forms corresponding to each flow state were generated in an in vitro flow loop and a photographic flow visualization technique was employed to measure wall shear rate. The results indicate a zone of low mean wall shear stress and highly oscillatory shear stress on the outer (lateral) wall of the bifurcation. In this zone, the mean wall shear stress became negative for all three hemodynamic states indicating flow separation. However, the spatial extent of the flow separation zone was not affected significantly by the flow state. The study also revealed a large spatial variation of the phase angle between the hoop strain (circumferential strain due to radial artery expansion) and the wall shear stress, the two main mechanical stimuli acting on endothelial cells which affect their biology. In the zone of low mean wall shear stress on the outer wall, the two stimuli were more out of phase relative to the mother branch, whereas they were less out of phase (by about 50 degrees) on the inner wall (flow divider side). This phase angle was affected significantly by the flow state. For angiotensin II, the phase angle reached a maximum of 125 degrees in the low mean shear zone while the maximum was 94 degrees and 66 degrees for the normal and isoproterenol states, respectively. Our observation that large phase angles between the hoop strain and wall shear stress wave forms are localized in the low shear stress region where atherosclerotic disease occurs suggests the possible physiological relevance of this phase angle to the development of atherosclerosis.

Angiotensin II↗

A microstructural model of elastostatic properties of articular cartilage in confined compression.

A microstructural model of cartilage was developed to investigate the relative contribution of tissue matrix components to its elastostatic properties. Cartilage was depicted as a tensed collagen lattice pressurized by the Donnan osmotic swelling pressure of proteoglycans. As a first step in modeling the collagen lattice, two-dimensional networks of tensed, elastic, interconnected cables were studied as conceptual models. The models were subjected to the boundary conditions of confined compression and stress-strain curves and elastic moduli were obtained as a function of a two-dimensional equivalent of swelling pressure. Model predictions were compared to equilibrium confined compression moduli of calf cartilage obtained at different bath concentrations ranging from 0.01 to 0.50 M NaCl. It was found that a triangular cable network provided the most consistent correspondence to the experimental data. The model showed that the cartilage collagen network remained tensed under large confined compression strains and could therefore support shear stress. The model also predicted that the elastic moduli increased with increasing swelling pressure in a manner qualitatively similar to experimental observations. Although the model did not preclude potential contributions of other tissue components and mechanisms, the consistency of model predictions with experimental observations suggests that the cartilage collagen network, prestressed by proteoglycan swelling pressure, plays an important role in supporting compression.

Animals↗