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T Varghese

Publications and source records attributed to T Varghese.

At least 37 records · Page 2Linked to original sources

Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node.

Mathematical models of the action potential in the periphery and center of the rabbit sinoatrial (SA) node have been developed on the basis of published experimental data. Simulated action potentials are consistent with those recorded experimentally: the model-generated peripheral action potential has a more negative takeoff potential, faster upstroke, more positive peak value, prominent phase 1 repolarization, greater amplitude, shorter duration, and more negative maximum diastolic potential than the model-generated central action potential. In addition, the model peripheral cell shows faster pacemaking. The models behave qualitatively the same as tissue from the periphery and center of the SA node in response to block of tetrodotoxin-sensitive Na(+) current, L- and T-type Ca(2+) currents, 4-aminopyridine-sensitive transient outward current, rapid and slow delayed rectifying K(+) currents, and hyperpolarization-activated current. A one-dimensional model of a string of SA node tissue, incorporating regional heterogeneity, coupled to a string of atrial tissue has been constructed to simulate the behavior of the intact SA node. In the one-dimensional model, the spontaneous action potential initiated in the center propagates to the periphery at approximately 0.06 m/s and then into the atrial muscle at 0.62 m/s.

Action Potentials↗

Theoretical bounds on the estimation of transverse displacement, transverse strain and Poisson's ratio in elastography.

The Cramér-Rao Lower Bounds (CRLB) are derived for the displacement and strain estimation in directions orthogonal to the ultrasonic beam axis, using a previously-described recorrelation method of axial, lateral and elevational motion estimation. We also compare it to the lateral tracking method that involves the sole use of the axial signal in the transverse direction. Our theoretical results, verified with simulations and phantom experiments, show that elastography is capable of measuring axial and transverse strain at up to 10% axially applied compression. Finally, we predict the performance of the estimation of the Poisson's ratio using decoupled axial and lateral estimates that result from the recorrelation method.

Computer Simulation↗

Power spectral strain estimators in elastography.

Elastography can produce quality strain images in vitro and in vivo. Standard elastography uses a coherent cross-correlation technique to estimate tissue displacement and tissue strain using a subsequent gradient operator. Although coherent estimation methods generally have the advantage of being highly accurate and precise, even relatively small undesired motions are likely to cause enough signal decorrelation to produce significant degradation of the elastogram. For elastography to become more universally practical in such applications as hand-held, intravascular and abdominal imaging, the limitations associated with coherent strain estimation methods that require tissue and system stability, must be overcome. In this paper, we propose the use of a spectral-shift method that uses a centroid shift estimate to measure local strain directly. Furthermore, we also show theoretically that a spectral bandwidth method can also provide a direct strain estimation. We demonstrate that strain estimation using the spectral-shift technique is moderately less precise, but far more robust than the cross-correlation method. A theoretical analysis, simulations and experimental results are used to illustrate the properties associated with this method.

Elasticity↗

A method for experimental characterization of the noise performance of elastographic systems.

Characterization of the noise performance of the elastographic system is necessary to evaluate the accuracy and precision of the estimated strain. The elastographic system includes the ultrasonic scanner, the computer controlled compression device and the strain estimation algorithm. In this paper, we present a method of characterizing the elastographic system experimentally using a uniformly elastic homogenous tissue-mimicking phantom. The strain response of the elastographic system is evaluated by characterizing the accuracy and precision of the strain estimates for a large range of input strains. The experimental results obtained follow the theoretical predictions obtained using the Strain Filter (SF) concept for the cross-correlation based strain estimator. In this paper, we illustrate the application of the Experimental Strain Response (ESR) to characterize strain estimation at the focus of the transducer and the axis of symmetry of the phantom.

Elasticity↗

Elastography: ultrasonic estimation and imaging of the elastic properties of tissues.

The basic principles of using sonographic techniques for imaging the elastic properties of tissues are described, with particular emphasis on elastography. After some preliminaries that describe some basic tissue stiffness measurements and some contrast transfer limitations of strain images are presented, four types of elastograms are described, which include axial strain, lateral strain, modulus and Poisson's ratio elastograms. The strain filter formalism and its utility in understanding the noise performance of the elastographic process is then given, as well as its use for various image improvements. After discussing some main classes of elastographic artefacts, the paper concludes with recent results of tissue elastography in vitro and in vivo.

Animals↗

Anti-C1q antibody as a marker of disease activity in systemic lupus erythematosus.

The present study was conducted to examine the usefulness of anti-C1q antibody as a marker of disease activity in Indian patients with systemic lupus erythematosus (SLE). We standardized the assay for detection of IgG anti-C1q antibody using ELISA. The normal cut-off level was determined by testing 57 healthy, age and sex matched controls to be 53 units/m1 (mean +/- 2 SD). Patients with SEL (97 females and 13 males) were studied and the following parameters were obtained on all: SLE disease activity index (SLEDAI), anti-C1q, anti-ds DNA and C3. Correlations were tested between these parameters using Spearman's rank correlation coefficients. Anti-C1q was found positive in 66 (60%) patients while anti-ds DNA was found in 78 (71%). The positive predictive values of anti-C1q and anti-ds DNA for lupus nephritis were 59 and 61 per cent respectively. The titres of anti-C1q correlated positively with SLEDAI (P < 0.01) and anti-ds DNA (P < 0.01) and negatively with C3 levels (P < 0.001). No significant correlation was observed between anti-C1q positivity and any particular organ involvement. Similarly, no correlation was found between anti-C1q and proliferative lupus nephritis. Anti-C1q was found positive in 5 of 9 patients with moderate SLEDAI scores and negative for anti-ds DNA antibody. It is concluded that anti-C1q antibody can serve as a general marker for lupus activity, supplementing the currently used serum markers.

Adolescent↗

Characterization of elastographic noise using the envelope of echo signals.

A theoretical formulation characterizing the noise performance of strain estimation using envelope signals is presented for the cross-correlation based strain estimator in elastography, using a modified strain filter approach. The strain filter describes the relationship among the elastographic signal-to-noise ratio (SNRe), sensitivity, contrast-to-noise ratio and dynamic range for a given resolution in the elastogram, as determined by the cross-correlation window length and window overlap. Theoretical results indicate that the envelope strain filter noise performance (SNRe level) is about half that obtained in the ratio frequency (RF) case (fo = 7.5 MHz). Simulation results corroborate the trend predicted using the strain filter. Experimental SNRe vs. strain plots presented in this article illustrate the same trend as the theoretical results. These plots allow a quantitative comparison of the elastograms obtained with RF and envelope signal processing. For small strains, the performance obtained using RF signals is superior to that obtained for envelope signals (since jitter errors are smaller due to the utilization of phase information in RF signals). However, for large tissue strains, envelope analysis provides an accurate estimate of the tissue strain (since envelope signal decorrelation is smaller than RF signal decorrelation at large strains). An algorithm that combines the low-noise characteristics of the cross-correlation analysis using RF signals at small strains and envelope signals for estimation of large tissue strains is proposed to improve the dynamic range in the elastogram.

Algorithms↗

An analysis of elastographic contrast-to-noise ratio.

We present a theoretical formalism and simulation results that allow the incorporation of the elastic contrast properties of tissues with simple geometries into the elastographic noise models developed previously. This analysis results in the computation of the elastographic contrast-to-noise ratio (CNRe). The CNRe in elastography is an important quantity that is related to the detectability of a lesion or inhomogeneity. In this paper, the upper bound on the elastographic CNRe is derived for both a one-dimensional (1-D) and 2-D analytic plane-strain tissue model. The CNRe in the elastogram depends on the contrast-transfer efficiency (CTE) for both the 1-D and 2-D geometries discussed in this paper. The 1-D model is used to characterize layered structures and the 2-D model is derived for circular inclusion within a background of uniform elasticity. A previously derived classical analytic solution of the elasticity equations, for a circular inclusion embedded in an infinite medium and subjected to a uniaxial compression, is used to compute the upper bound of the CNRe. Monte Carlo simulations illustrate the close correspondence between the theoretical and simulation results.

Elasticity↗

The nonstationary strain filter in elastography: Part II. Lateral and elevational decorrelation.

The nonstationary evolution of the strain filter due to lateral and elevational motion of the tissue scatterers across the ultrasound beam is analyzed for the 1-D cross-correlation-based strain estimator. The effective correlation coefficient that includes the contributions due to lateral and elevational signal decorrelation is used to derate the upper bound of the signal-to-noise ratio in the elastogram (SNRe) predicted by the ideal strain filter. In the case of an elastically homogeneous target, if the transducer is on the axis of symmetry of such target in the elevational direction, the motion of the scatterers out the imaging plane is minimized. In addition, the ultrasound beam along the elevational direction is broader, allowing scatterers to stay longer within the beam during tissue compression. Under these conditions, lateral signal decorrelation becomes the primary contributor to the nonstationary behavior of the strain filter. Both the elastographic SNRe and the dynamic range are reduced, with an increase in lateral decorrelation. Finite element simulations and phantom experiments are presented in this paper to corroborate the theoretical strain filter. The nonstationary behavior of the strain filter is reduced by confining the tissue in the lateral direction (minimizing motion of tissue scatterers), thereby improving the quality of the elastogram.

Computer Simulation↗

The nonstationary strain filter in elastography: Part I. Frequency dependent attenuation.

The accuracy and precision of the strain estimates in elastography depend on a myriad number of factors. A clear understanding of the various factors (noise sources) that plague strain estimation is essential to obtain quality elastograms. The nonstationary variation in the performance of the strain filter due to frequency-dependent attenuation and lateral and elevational signal decorrelation are analyzed in this and the companion paper for the cross-correlation-based strain estimator. In this paper, we focus on the role of frequency-dependent attenuation in the performance of the strain estimator. The reduction in the signal-to-noise ratio (SNRs) in the RF signal, and the center frequency and bandwidth downshift with frequency-dependent attenuation are incorporated into the strain filter formulation. Both linear and nonlinear frequency dependence of attenuation are theoretically analyzed. Monte-Carlo simulations are used to corroborate the theoretically predicted results. Experimental results illustrate the deterioration in the precision of the strain estimates with depth in a uniformly elastic phantom. Theoretical, simulation and experimental results indicate the importance of high SNRs values in the RF signals, because the strain estimation sensitivity, elastographic SNRe and dynamic range deteriorate rapidly with a decrease in the SNRs. In addition, a shift in the strain filter toward higher strains is observed at large depths in tissue due to the center frequency downshift.

Computer Simulation↗

Elastographic dynamic range expansion using variable applied strains.

In elastography, we want to image the entire range of stiffnesses of the elastic components found in inhomogeneous tissues. In order to achieve this, the elastographic dynamic range should equal the entire stiffness dynamic range in the target. Various sources of noise limit the dynamic range of elastography. The recently-defined strain filter concept offers an analytical and graphical way of observing these limitations. In this paper, we describe a method that achieves the expansion of the elastographic dynamic range. It involves the application of variable strains in combination with selective storage of strain data that have optimal elastographic signal-to-noise ratios. This expands the current dynamic range of elastography by orders of magnitude when compared to single compression elastography. The process is explained theoretically using the strain filter framework, and 1 D as well as 2D tissue simulations are used to corroborate the theory.

Algorithms↗

The effects of extended evaluation on depressive symptoms in children and adolescents.

A sample of 137 child and adolescent outpatients with major depressive disorder were examined to identify baseline clinical characteristics that predicted symptom severity at the end of a 3-week evaluation period and to determine whether change in symptom severity between week 1 and week 2 predicted symptom severity at week three. Subjects underwent three consecutive weekly evaluations prior to being considered for entry into a double-blind, placebo-controlled treatment trial of fluoxetine. Results indicated that the combination of age, social functioning, family history, Children's Depressive Rating Scale-Revised (CDRS-R) (Poznanski et al. (1985) Psychopharmacol. Bull. 21, 979-989) total score at visit one, and percent change in symptom severity between visit one and visit two were predictors of symptom severity at visit three. These findings suggest that (1) subjects should not be excluded from randomized controlled clinical treatment trials based solely on improvement of symptom severity between visits and (2) an extended evaluation period is warranted, especially for adolescents whose symptom severity tends to fluctuate from week to week.

Adolescent↗

Noise reduction in elastograms using temporal stretching with multicompression averaging.

Elastography uses estimates of the time delay (obtained by cross-correlation) to compute strain estimates in tissue due to quasistatic compression. Because the time delay estimates do not generally occur at the sampling intervals, the location of the cross-correlation peak does not give an accurate estimate of the time delay. Sampling errors in the time-delay estimate are reduced using signal interpolation techniques to obtain subsample time-delay estimates. Distortions of the echo signals due to tissue compression introduce correlation artifacts in the elastogram. These artifacts are reduced by a combination of small compressions and temporal stretching of the postcompression signal. Random noise effects in the resulting elastograms are reduced by averaging several elastograms, obtained from successive small compressions (assuming that the errors are uncorrelated). Multicompression averaging with temporal stretching is shown to increase the signal-to-noise ratio in the elastogram by an order of magnitude, without sacrificing sensitivity, resolution or dynamic range. The strain filter concept is extended in this article to theoretically characterize the performance of multicompression averaging with temporal stretching.

Algorithms↗

Estimating tissue strain from signal decorrelation using the correlation coefficient.

A simple relationship between the correlation coefficient and the applied strain, applicable only at low strains, is presented in this article. This relationship is derived for a Gaussian modulated cosine point spread function. The performance of the strain estimator is analyzed using a theoretical expression for the correlation coefficient along with simulation and experimental results. Both the theoretical and simulation results diverge from the ideal relationship between the strain and the correlation coefficient as the applied strain is increased. Simulation results illustrate that the strain estimate obtained using the correlation coefficient is a biased estimate with a large variability. Experimental results, however, illustrate that strain estimation using the 1-D correlation coefficient estimate is applicable only at high signal-to-noise ratios in the radiofrequency signal and in the absence of lateral and elevational signal decorrelation.

Computer Simulation↗

An optimized index of human cardiovascular adaptation to simulated weightlessness.

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Adaptation, Physiological↗

Performance optimization in elastography: multicompression with temporal stretching.

A general theoretical framework known as the strain filter has been previously used to evaluate the performance in elastography. The strain filter describes the relationship among the resolution, dynamic range, sensitivity and elastographic SNR (SNRe), and may be plotted as a graph of the upper bound of the SNRe vs. the strain experienced by the tissue, for a desired elastographic axial resolution as determined by the data window length. The ideal strain filter has an infinitely high, flat all-pass characteristic shape in the strain domain, which means that all local tissue strains are displayed in the elastogram with infinite SNRe; it also means that the strain dynamic range in the elastogram is infinite as well. Practical strain filters obtained using a single tissue compression have a bandpass characteristic shape in the strain domain, where the -3 dB width of this bandpass characteristic may be defined as the elastographic dynamic range. In this paper, we present an optimal technique for stretching multicompression elastography, practiced by selecting the optimum incremental applied strain using the strain filter. Two techniques, temporal stretching and multicompression elastography, are combined in this paper to improve elastogram quality. Stretching multicompression elastography using the optimal applied strain increment alters the shape of the strain filter from its bandpass characteristic to a more desirable high-emphasis filter. The dynamic range of optimal stretching multicompress on elastography is limited only by tissue nonlinearities. This optimal applied strain increment minimizes signal decorrelation and achieves the maximum achievable elastographic SNRe.

Elastic Tissue↗

Mean-scatterer spacing estimates with spectral correlation.

An ultrasonic backscattered signal from material comprised of quasiperiodic scatterers exhibit redundancy over both its phase and magnitude spectra. This paper addresses the problem of estimating mean-scatterer spacing from the backscattered ultrasound signal using spectral redundancy characterized by the spectral autocorrelation (SAC) function. Mean-scatterer spacing estimates are compared for techniques that use the cepstrum and the SAC function. A -scan models consist of a collection of regular scatterers with Gamma distributed spacings embedded in diffuse scatterers with uniform distributed spacings. The model accounts for attenuation by convolving the frequency dependent scattering centers with a time-varying system response. Simulation results indicate that SAC-based estimates converge more reliably over smaller amounts of data than cepstrum-based estimates. A major reason for the performance advantage is the use of phase information by the SAC function, while the cepstrum uses a phaseless power spectral density that is directly affected by the system response and the presence of diffuse scattering (speckle). An example of estimating the mean-scatterer spacing in liver tissue also is presented.

Culture Techniques↗

Characterization of tissue microstructure scatterer distribution with spectral correlation.

Characterization of tissue microstructure from the backscattered ultrasound signal using the spectral autocorrelation (SAC) function provides information about the scatterer distribution in biological tissue. This paper demonstrates SAC capabilities in characterizing periodicities in A-scans due to regularity in the scatterer distribution. The A-scan is modelled as a cyclostationary signal, where the statistical parameters of the signal vary in time with single or multiple periodicities. This periodicity manifests itself as spectral peaks both in the power spectral density (PSD) and in the SAC. Periodicity in the PSD will produce a well defined dominant peak in the cepstrum, which has been used to determine the scatterer spacing. The relationship between the scatterer spacing and the spacing of the spectral peaks is established using a stochastic model of the echo-formation process from biological tissue. The distribution of the scatterers within the microstructure is modelled using a Gamma function, which offers a flexible method of simulating parametric regularity in the scatterer spacing. Simulations of the tissue microstructure for lower orders of regularity indicate that the SAC components reveal information about the scatterer spacing that are not seen in the PSD and the cepstrum. The echoformation process is tested by simulating microstructure of varying regularity and analyzing their effect on the SAC, PSD and cepstrum. Experimental validation of the simulation results are provided using in vivo scans of the breast and liver tissue that show the presence of significant spectral correlation components in the SAC.

Computer Simulation↗