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A comparison of quantitative measures of arterial tortuosity using sine wave simulations and 3D wire models.

This paper discusses the quantitative measurement of arterial tortuosity. The measures described are a tortuosity coefficient, TC, based on the second derivative of the vessel midline and the distance factor, DF, defined as L/D - 1, where L is the vessel length and D is the straight line distance between the vessel end points. A tortuosity scale derived from sine wave simulations was used to determine the ability of these two measures to quantify tortuosity. The tortuosity coefficient was demonstrated to be an appropriate measure whilst the distance factor was found to be a measure of vessel elongation rather than tortuosity. A tomographic method of deriving three-dimensional measures of TC and DF is described using a wire model. The x, y coordinates along the length of the wire were obtained from CT slices and the three-dimensional values calculated as the geometric mean of the TC and DF values measured in the x and y directions. Rotation of the wire through 90 degrees demonstrated that the three-dimensional derivations of TC and DF were independent of the orientation of the wire.

Arteries↗

Parsimonious basis selection in exponential spectral analysis.

Sums of decaying real exponentials (SDREs) are frequently used in models of time-varying processes. First-order compartmental models are widely employed to describe mass transit in chemical and biological systems. In these models the evolution of compartment concentration versus time is represented as the convolution of an input function with an SDRE. In exponential spectral analysis (ESA) the nonlinear problem of estimating the SDRE rate constants is replaced by the linear estimation of the coefficients of a preselected set of exponential basis functions (EBFs). This work addresses the problem of selecting the number of EBFs and the rate constant of each basis element. Basis dimension is established via model selection, in which approximation error and parameter redundancy are the criteria. The latter is estimated via simulation of the fitted model over multiple noise realizations. A constrained Cramér-Rao lower bound is derived for ESA parameters. The resulting parsimonious ESA algorithm (PESA) ameliorates the inherent problem of non-uniqueness in ESA parameters. Consequently, sets of time series may be compared in a statistically meaningfully way in terms of physically or physiologically significant parameters. PESA is applied to compare the retention of two radiotracers in the artificially perfused rabbit heart.

Algorithms↗

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling.

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.

Adolescent↗

Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study.

Re-entry is an important mechanism of cardiac arrhythmias. During re-entry a wave of electrical activation repeatedly propagates into recovered tissue, rotating around a rod-like filament. Breakdown of a single re-entrant wave into multiple waves is believed to underlie the transition from ventricular tachycardia to ventricular fibrillation. Several mechanisms of breakup have been identified including the effect of anisotropic conduction in the ventricular wall. Cells in the inner and outer layers of the ventricular wall have different action potential durations (APD), and support re-entrant waves with different periods. The aim of this study was to use a computational approach to study twisting and breakdown in a transmural re-entrant wave spanning these regions, and examine the relative role of this effect and anisotropic conduction. We used a simplified model of action potential conduction in the ventricular wall that we modified so that it supported stable re-entry in an anisotropic model with uniform APD. We first examined the effect of regional differences on breakdown in an isotropic model with transmural differences in APD, and found that twisting of the re-entrant filament resulted in buckling and breakdown during the second cycle of re-entry. We found that breakdown was amplified in the anisotropic model, resulting in complex activation in the region of longest APD. This study shows that regional differences in cardiac electrophysiology are a potentially important mechanism for destabilizing re-entry and may act synergistically with other mechanisms to mediate the transition from ventricular tachycardia to ventricular fibrillation.

Action Potentials↗

Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia.

The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.

Acute Disease↗

Simulation of a plane wavefront propagating in cardiac tissue using a cellular automata model.

We present a detailed description of a cellular automata model for the propagation of action potential in a planar cardiac tissue, which is very fast and easy to use. The model incorporates anisotropy in the electrical conductivity and a spatial variation of the refractory time. The transmembrane potential distribution is directly derived from the cell states, and the intracellular and extracellular potential distributions are calculated for the particular case of a plane wavefront. Once the potential distributions are known, the associated current densities are calculated by Ohm's law, and the magnetic field is determined at a plane parallel to the cardiac tissue by applying the law of Biot and Savart. The results obtained for propagation speed and for magnetic field amplitude with the cellular automata model are compared with values predicted by the bidomain formulation, for various angles between wavefront propagation and fibre direction, characterizing excellent agreement between the models.

Action Potentials↗

Influence of the scalp thickness on the intracranial contribution to rheoencephalography.

In spite of the great efforts made by the scientific community, up to now there is no agreement about the rheoencephalography (REG) capability to reflect cerebral blood flow (CBF). Moreover, a standard procedure and the optimal electrode arrangement have not been established yet. In a previous study, we found, using a classical four-shell spherical model of the head and solving it by numerical methods that, theoretically, there could exist an electrode arrangement to register an REG II free of extracranial contribution. In this paper, we have studied the influence of scalp thickness on the intracranial contribution to REG II. The study has been performed by solving the head model, using in this case analytical methods, and then estimating the partial contribution of CBF pulsatility to REG for a given set of scalp thicknesses. Although our theoretical results validate the previous finding and suggest that, in some cases, an optimal electrode arrangement to register REG II exists, such an arrangement, and even its existence, is very sensitive to the subject's scalp thickness. According to this, there could not exist a universal electrode arrangement suitable for all individuals to register an REG II free of extracranial contribution, since it depends on the subject's physical constitution. This fact could explain the lack of agreement in the literature about REG interpretation.

Brain↗

Translational and Brownian motion in laser-Doppler flowmetry of large tissue volumes.

This study reports the derivation of a precise mathematical relationship existing between the different p-moments of the power spectrum of the photoelectric current, obtained from a laser-Doppler flowmeter (LDF), and the red blood cell speed. The main purpose is that both the Brownian (defining the 'biological zero') and the translational movements are taken into account, clarifying in this way what the exact contribution of each parameter is to the LDF derived signals. The derivation of the equations is based on the quasi-elastic scattering theory and holds for multiple scattering (i.e. measurements in large tissue volumes and/or very high red blood cell concentration). The paper also discusses why experimentally there exists a range in which the relationship between the first moment of the power spectrum and the average red blood cells speed may be considered as 'linear' and what are the physiological determinants that can result in nonlinearity. A correct way to subtract the biological zero from the LDF data is also proposed. The findings should help in the design of improved LDF instruments and in the interpretation of experimental data.

Animals↗

A novel approach for the averaging of magnetocardiographically recorded heart beats.

Performing signal averaging in an efficient and correct way is indispensable since it is a prerequisite for a broad variety of magnetocardiographic (MCG) analysis methods. One of the most common procedures for performing the signal averaging to increase the signal-to-noise ratio (SNR) in magnetocardiography, as well as in electrocardiography (ECG), is done by means of spatial or temporal techniques. In this paper, an improvement of the temporal averaging method is presented. In order to obtain an accurate signal detection, temporal alignment methods and objective classification criteria are developed. The processing technique based on hierarchical clustering is introduced to take into account the non-stationarity of the noise and, to some extent, the biological variability of the signals reaching the optimum SNR. The method implemented is especially designed to run fast and does not require any interaction from the operator. The averaging procedure described in this work is applied to the averaging of MCG data as an example, but with its intrinsic properties it can also be applied to the averaging of ECG recording, averaging of body-surface-potential mapping (BSPM) and averaging of magnetoencephalographic (MEG) or electroencephalographic (EEG) signals.

Algorithms↗

Simulation of voltage-sensitive optical signals in three-dimensional slabs of cardiac tissue: application to transillumination and coaxial imaging methods.

Voltage-sensitive dyes are an important tool in visualizing electrical activity in cardiac tissue. Until today, they have mainly been applied in cardiac electrophysiology to subsurface imaging. In the present study, we assess different imaging methods used in optical tomography with respect to their effectiveness in visualizing 3D cardiac activity. To achieve this goal, we simulate optical signals produced by excitation fronts initiated at different depths inside the myocardial wall and compare their properties for various imaging modes. Specifically, we consider scanning and broad-field illumination, including trans- and epi-illumination. We focus on the lateral optical resolution and signal intensity, as a function of the source depth. Optical diffusion theory is applied to derive a computationally efficient approximation of the point-spread function and to predict voltage-sensitive signals. Computations were performed both for fluorescent and absorptive voltage-sensitive dyes. Among all the above-mentioned methods, fluorescent coaxial scanning yields the best resolution (<2.5 mm) and gives the most information about the intramural cardiac activity.

Action Potentials↗

Localization of the site of origin of reentrant arrhythmia from body surface potential maps: a model study.

We have developed a model-based imaging approach to estimate the site of origin of reentrant arrhythmia from body surface potential maps (BSPMs), with the aid of a cardiac arrhythmia model. The reentry was successfully simulated and maintained in the cardiac model, and the simulated ECG waveforms over the body surface corresponding to a maintained reentry have evident characteristics of ventricular tachycardia. The performance of the inverse imaging approach was evaluated by computer simulations. The present simulation results show that an averaged localization error of about 1.5 mm, when 5% Gaussian white noise was added to the BSPMs, was detected. The effects of the heart-torso geometry uncertainty on the localization were also initially assessed and the simulation results suggest that no significant influence was observed when 10% torso geometry uncertainty or 10 mm heart position shifting was considered. The present simulation study suggests the feasibility of localizing the site of origin of reentrant arrhythmia from non-invasive BSPMs, with the aid of a cardiac arrhythmia model.

Arrhythmias, Cardiac↗

Extraction of foetal ECG by combination of singular value decomposition and neuro-fuzzy inference system.

Extraction of foetal ECG that is embedded in the maternal ECG is a challenging problem. This paper presents a combined system to extract foetal ECG from maternal abdominal ECG. The system uses a combination of singular value decomposition (SVD) and a neuro-fuzzy inference system. The SVD is used to construct two reference signals, while the fuzzy system is used as an adaptive canceller. The algorithm is applied on synthetic as well as real data and the results are presented. In addition, the paper presents an example of using the same system as a noise removal tool.

Algorithms↗

Estimating perfusion using microCT to locate microspheres.

The injection of microspheres into the blood stream has been a common method to measure the spatial distribution of blood flow (perfusion). A technique to conduct this kind of measurement in small animal organs is presented using silver-coated microspheres with a diameter of 16 microm and high-resolution computed tomography (microCT) to detect individual microspheres. Phantom experiments demonstrate the detectability of individual spheres. The distribution of microspheres within a rat heart is given as an example. Using non-destructive, three-dimensional imaging for microsphere detection avoids the cumbersome dissection of the organ into samples or slices and their subsequent registration. The detection of individual spheres allows high-resolution measurements of perfusion and arbitrary definition of regions of interest. These, in turn, allow for accurate statistical analysis of perfusion such as relative dispersion curves.

Animals↗

Decomposition of a laser-Doppler spectrum for estimation of speed distribution of particles moving in an optically turbid medium: Monte Carlo validation study.

A method for measurement of distribution of speed of particles moving in an optically turbid medium is presented. The technique is based on decomposition of the laser-Doppler spectrum. The theoretical background is shown together with the results of Monte Carlo simulations, which were performed to validate the proposed method. The laser-Doppler spectra were obtained by Monte Carlo simulations for assumed uniform and Gaussian speed distributions of particles moving in the turbid medium. The Doppler shift probability distributions were calculated by Monte Carlo simulations for several anisotropy factors of the medium, assuming the Hanyey-Greenstein phase function. The results of the spectra decomposition show that the calculated speed distribution of moving particles match well the distribution assumed for Monte Carlo simulations. This result was obtained for the spectra simulated in optical conditions, in which the photon is scattered with the Doppler shift not more than once during its travel between the source and detector. Influence of multiple scattering of the photon is analysed and a perspective of spectrum decomposition under such conditions is considered. Potential applications and limitations of the method are discussed.

Blood Flow Velocity↗

Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions.

In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

Action Potentials↗

Left ventricular motion reconstruction with a prolate spheroidal B-spline model.

Tagged cardiac magnetic resonance (MR) imaging can non-invasively image deformation of the left ventricular (LV) wall. Three-dimensional (3D) analysis of tag data requires fitting a deformation model to tag lines in the image data. In this paper, we present a 3D myocardial displacement and strain reconstruction method based on a B-spline deformation model defined in prolate spheroidal coordinates, which more closely matches the shape of the LV wall than existing Cartesian or cylindrical coordinate models. The prolate spheroidal B-spline (PSB) deformation model also enforces smoothness across and can compute strain at the apex. The PSB reconstruction algorithm was evaluated on a previously published data set to allow head-to-head comparison of the PSB model with existing LV deformation reconstruction methods. We conclude that the PSB method can accurately reconstruct deformation and strain in the LV wall from tagged MR images and has several advantages relative to existing techniques.

Algorithms↗

A comparison of normal and tangential magnetic field component measurements in biomagnetic investigations.

Because of the way most available hardware gradiometers are designed and in view of the prediction, by theory, that the normal magnetic field component provides all available information on the intrinsic current source, MEG and MCG measurements generally consider only the field vector normal to the head or truck surface. However, when looking for single events, the information contained in the normal component often cannot be fully sampled, because the sensor array has limited dimensions and therefore covers only a fraction of the field's spatial extension. Simulation of a current dipole in a sphere using realistic parameters shows that there is a considerable area where the amplitude of the tangential field components is larger than that of the normal one. Measurements using a 28-channel magnetometer system with normal and tangential pick-up coils and a current dipole in a phantom model confirm this prediction; depending on dipole orientation, the signal-to-noise ratio (SNR) could improve by a factor of up to 20 if the total field was considered instead of only the normal component. MCG recordings with the same instrument demonstrated a broad area above the heart where the tangential SNR was clearly better than the normal one. Preliminary measurements indicate that tangential components can also be recorded in the MEG; it is suggested that they may help source localisation.

Brain↗

Cerebral blood volume measurements using dynamic contrast-enhanced x-ray computed tomography: application to isoflurane anaesthetic studies.

A convenient and simple method of measuring cerebral blood volume (CBV) will aid in the clinical management of patients with cerebrovascular diseases and head trauma. Using a two-compartment model to characterize the distribution of x-ray contrast agent in the brain, we have developed a non-equilibrium (dynamic) x-ray CT method to measure CBV and have applied this method to study the effects of isoflurane. CBV and cerebral blood flow (CBF, ex vivo) measurements were made in two groups of New Zealand White rabbits at varying (study group) and constant (control group) arterial CO2 concentration. ANOVA for repeated measures was used on the control data to determine the precision of our two-compartment CT-CBV method. The results showed that the precision of our CT-CBV measurement was 9.8%. In addition a paired t-test analysis of the control data revealed that the duration of isoflurane anaesthesia had no effect on the repeated measurements of CBV or CBF. The rate of change in CBV (0.049 ml/100 g/mmHg) and CBF (6.2 ml/min/100 g/mmHg) with respect to changes in arterial CO2 concentration under the influence of isoflurane anaesthesia was similar to those reported in previous studies, thus validating our experimental CT-CBV and CBF measurements. Our CT-CBV method will lead to more information on the relationship between CBV and CBF under different pharmacological interventions in both normal and disease conditions.

Analysis of Variance↗