Biomedical subjects

Dan Adam

Publications and source records attributed to Dan Adam.

At least 19 recordsLinked to original sources

PubMed2006

The effects of albumin-coated microbubbles in DNA delivery mediated by therapeutic ultrasound.

The application of therapeutic ultrasound (TUS) in combination with contrast agents (USCA) to mediate gene delivery relies on the understanding of the bioeffects involved. The objective of this study was to evaluate the various bioeffects generated by albumin-coated microbubbles: Optison, an USCA, when applied with TUS operated for 10-30 min, on cells and on DNA transfection. This study reveals that Optison microbubbles were still acoustically active after long-term TUS application of 30 min. Optison enhances TUS-gene transfection by increasing the number of plasmids in the cells and also by distributing the plasmids to more cells, without significant decrease in cell viability. Optison also interacts with the DNA to further enhance transfection in a mechanism not necessarily involving cavitation. However, Optison affects mainly the cell cytoplasmatic membrane, without interfering with DNA intracellular trafficking. Using high-resolution scanning electron microscopy (HRSEM), the bioeffects on cell membrane induced by TUS-Optison were observed, demonstrating that Optison lead to a rougher surface, characterized by depressions that are reversible within 24-h post TUS. These effects are different from those observed when only TUS was applied. The findings from this study suggest that albumin-coated microbubbles enhances transfection when using TUS for 10-30 min, and that microbubbles play a major role in elevating cell transfection level and efficiency.

Albumins↗

PubMed2006

Assessment of myocardial regional strain and strain rate by tissue tracking in B-mode echocardiograms.

To date, established ultrasonic methods for myocardial regional deformation recovery are based on the Doppler effect, which has inherent limitations restricting its accuracy and use. The reported time domain methods show in vivo insufficient accuracy. A novel approach is elaborated mimicking the human observer who reaches robust diagnosis upon the B-mode data. In a region-of-interest (ROI), acoustic markers stable for tracking are selected. A weighting index presenting the quality of tracking of each marker is used for spatial polynomial fitting. For the feasibility study, a simple straight ROI was selected, which matches the septum. A thorough proof of concept is provided by comparing with a gold standard method and by applying the method to clinical datasets. The peak systolic longitudinal strains of 12 normals were -15% + -2.3% and, of 12 patients with a light-to-mild dysfunction of the apical-septal segment, they were -9% + -0.8% (p < 0.05). Enhancements of the method using spline fitting are introduced.

Algorithms↗

PubMed2005

The combined effect of spatial compounding and nonlinear filtering on the speckle reduction in ultrasound images.

Recently, a spatial compounding ultrasound imaging method was presented that utilizes a conventional 64-element phased array transducer with two unfocused pistons, each placed at one of the sides of the phased array transducer. This method is augmented here by inclusion of nonlinear filtering of the compounded images. The combined effects of the specific spatial compounding and nonlinear filtering on speckle reduction in the generated ultrasound images are studied and evaluated in two stages: First, the image quality is studied when nonlinear filtering is used as part of the spatial compounding. The study is performed by simulations using the Field II program, by processing several B-mode images of a kidney. The second stage compares the results obtained by the simulations to those obtained by in vitro laboratory experiments. Five different compounding strategies and two nonlinear filters, Gaussian and anisotropic diffusion, are investigated and evaluated in terms of image quality parameters-contrast and signal-to-noise ratio. It is shown that the combination of "averaging+nonlinear Gaussian filtering" produces the greatest improvement of image quality. When compared to a conventional phased array imaging system, the spatial compounding method that includes the conventional 64-element phased array transducer with two unfocused pistons, and employs the "averaging+nonlinear Gaussian filtering" strategy, obtains improvement in SNR that has reached 334%. Thus, though this method necessitates a somewhat wider probe, it produces significantly improved images.

Computer Simulation↗

PubMed2005

Optimization of sparse synthetic transmit aperture imaging with coded excitation and frequency division.

An effective aperture approach is used for optimization of a sparse synthetic transmit aperture (STA) imaging system with coded excitation and frequency division. A new two-stage algorithm is proposed for optimization of both the positions of the transmit elements and the weights of the receive elements. In order to increase the signal-to-noise ratio in a synthetic aperture system, temporal encoding of the excitation signals is employed. When comparing the excitation by linear frequency modulation (LFM) signals and phase shift key modulation (PSKM) signals, the analysis shows that chirps are better for excitation, since at the output of a compression filter the sidelobes generated are much smaller than those produced by the binary PSKM signals. Here, an implementation of a fast STA imaging is studied by spatial encoding with frequency division of the LFM signals. The proposed system employs a 64-element array with only four active elements used during transmit. The two-dimensional point spread function (PSF) produced by such a sparse STA system is compared to the PSF produced by an equivalent phased array system, using the Field II simulation program. The analysis demonstrates the superiority of the new sparse STA imaging system while using coded excitation and frequency division. Compared to a conventional phased array imaging system, this system acquires images of equivalent quality 60 times faster, when the transmit elements are fired in pairs consecutively and the power level used during transmit is very low. The fastest acquisition time is achieved when all transmit elements are fired simultaneously, which improves detectability, but at the cost of a slight degradation of the axial resolution. In real-time implementation, however, it must be borne in mind that the frame rate of a STA imaging system depends not only on the acquisition time of the data but also on the processing time needed for image reconstruction. Comparing to phased array imaging, a significant increase in the frame rate of a STA imaging system is possible if and only if an equivalent time efficient algorithm is used for image reconstruction.

Models, Theoretical↗

PubMed2005

On the relationship between encapsulated ultrasound contrast agent and pressure.

Noninvasive measurement of pressure within the heart cavities and other internal organs (e.g., kidney, liver) has significant clinical value, but currently is not feasible. Noninvasive pressure estimation using encapsulated ultrasound (US) contrast agents (UCA) as sensors is a challenge because they supposedly respond to their ambient pressure, but they are more rigid and less sensitive to pressure than gas microbubbles. Here, Optison sensitivity was studied (f(resonance) = approximately 2 MHz) to varying pressures, when excited at 2 times and also at 0.5 times f(resonance). Cyclic momentary increases in ambient pressure of 0 to 5, 0 to 10, 0 to 15 or 0 to 20 kPa at 1.0 Hz, mimicking left ventricular (LV) pressure changes, caused amplitude decrease of echoes at 0.5, 1 and 2 times the transmitted frequency and decrease of attenuation. Changes at 0.5 times the transmitted frequency correlated best, but only after 70 to 150 s. The correlations (mean +/- SD) during 150 to 300 s were 0.706 +/- 0.072 for 0 to 10 kPa, 0.844 +/- 0.042 for 0 to 15 kPa and 0.859 +/- 0.031 for 0 to 20 kPa. Attenuation presented less correlation. For 1.0 Hz, 10 to 15 kPa or 15 to 20 kPa pressures, mimicking systemic pressures, the attenuation decayed fast and even faster for slow (0.05 Hz) cyclic varying pressures, or elevated steady-state pressures (of 10 kPa and 20 kPa). Thus, cyclic pressure effects on UCA are demonstrated to be reversible, but elevated static pressures cause UCA destruction. This allows cyclic pressure variations to be detected, using the subharmonics of the transmitted frequency, down to 10 kPa.

Albumins↗

PubMed2005

Time and pressure dependence of acoustic signals radiated from microbubbles.

Encapsulated microbubbles are considered to be microsensors for in vivo blood pressure measurements in the cardiovascular system. To study the potential of this method, we developed a simulation and an experimental set-up that relate various characteristics of radiated acoustic signals from the microbubbles to the varying ambient pressure. Both the simulation and the experiment show that the radiated pressure from microbubbles generates a significant subharmonic component, which is modulated by changes in the ambient pressure. A time-dependent decrease of the steady-state radii within a population of microbubbles causes a phase reversal phenomenon, which explains the observed time delay in the build-up of the subharmonic modulation response. Additionally, we identify a frequency-capturing effect that indicates the termination of the nonlinear behavior of the microbubbles. Our research suggests that these subharmonic signals can be used for in vivo blood pressure measurements and highlights some of the considerations that need to be addressed in developing such techniques.

Albumins↗

PubMed2005

A novel approach to the 2-D blind deconvolution problem in medical ultrasound.

The finite frequency bandwidth of ultrasound transducers and the nonnegligible width of transmitted acoustic beams are the most significant factors that limit the resolution of medical ultrasound imaging. Consequently, in order to recover diagnostically important image details, obscured due to the resolution limitations, an image restoration procedure should be applied. The present study addresses the problem of ultrasound image restoration by means of the blind-deconvolution techniques. Given an acquired ultrasound image, algorithms of this kind perform either concurrent or successive estimation of the point-spread function (PSF) of the imaging system and the original image. In this paper, a blind-deconvolution algorithm is proposed, in which the PSF is recovered as a preliminary stage of the restoration problem. As the accuracy of this estimation affects all the following stages of the image restoration, it is considered as the most fundamental and important problem. The contribution of the present study is twofold. First, it introduces a novel approach to the problem of estimating the PSF, which is based on a generalization of several fundamental concepts of the homomorphic deconvolution. It is shown that a useful estimate of the spectrum of the PSF can be obtained by applying a proper smoothing operator to both log-magnitude and phase of the spectra of acquired radio-frequency (RF) images. It is demonstrated that the proposed approach performs considerably better than the existing homomorphic (cepstrum-based) deconvolution methods. Second, the study shows that given a reliable estimate of the PSF, it is possible to deconvolve it out of the RF-image and obtain an estimate of the true tissue reflectivity function, which is relatively independent of the properties of the imaging system. The deconvolution was performed using the maximum a-posteriori (MAP) estimation framework for a number of statistical priors assumed for the reflectivity function. It is shown in a series of in vivo experiments that reconstructions based on the priors, which tend to emphasize the "sparseness" of the tissue structure, result in solutions of higher resolution and contrast.

Algorithms↗

PubMed2004

The combined effect of nonlinear filtration and window size on the accuracy of tissue displacement estimation using detected echo signals.

In cardiac elastography, the regional strain and strain rate imaging is based on displacement estimation of tissue sections within the heart muscle carried out with various block-matching techniques (cross-correlation, sum of absolute differences, sum of squared differences, etc.). The accuracy of these techniques depends on a combination of ultrasonic imaging parameters such as ultrasonic frequency of interrogation, signal-to-noise ratio, size of a kernel used in a block-matching algorithm, type of data and speckle decorrelation. In this paper, we discuss the possibility to enhance the accuracy of the displacement estimation via nonlinear filtering of B-mode images before block-matching operation. The combined effect of a filter algorithm and a kernel size on the accuracy of the displacement estimation is analyzed using a 36-frame sequence of grayscale B-mode images of a human heart acquired by an ultrasound system operating at 1.77 MHz. It is shown that the nonlinear filtering of images enables to obtain the desired accuracy (less than one pixel) of the displacement estimation with smaller kernels than without filtering. These results are obtained for two filters--an adaptive anisotropic diffusion filter and a nonlinear Gaussian filter chain.

Algorithms↗

PubMed2004

Parameter optimization of pulse compression in ultrasound imaging systems with coded excitation.

A linear array imaging system with coded excitation is considered, where the proposed excitation/compression scheme maximizes the signal-to-noise ratio (SNR) and minimizes sidelobes at the output of the compression filter. A pulse with linear frequency modulation (LFM) is used for coded excitation. The excitation/compression scheme is based on the fast digital mismatched filtering. The parameter optimization of the excitation/compression scheme includes (i) choice of an optimal filtering function for the mismatched filtering; (ii) choice of an optimal window function for tapering of the chirp amplitude; (iii) optimization of a chirp-to-transducer bandwidth ratio; (iv) choice of an appropriate n-bit quantizer. The simulation results show that the excitation/compression scheme can be implemented as a Dolph-Chebyshev filter including amplitude tapering of the chirp with a Lanczos window. An example of such an optimized system is given where the chirp bandwidth is chosen to be 2.5 times the transducer bandwidth and equals 6 MHz: The sidelobes are suppressed to -80 dB, for a central frequency of 4 MHz, and to -94 dB, for a central frequency of 8 MHz. The corresponding improvement of the SNR is 18 and 21 dB, respectively, when compared to a conventional short pulse imaging system. Simulation of B-mode images demonstrates the advantage of coded excitation systems of detecting regions with low contrast.

Journal Article↗

PubMed2004

Improving motion estimation by accounting for local image distortion.

Cardiac elastography is a useful diagnostic technique for detection of heart function abnormalities, based on analysis of echocardiograms. The analysis of the regional heart motion allows assessing the extent of myocardial ischemia and infarction. In this paper, a new two-stage algorithm for cardiac motion estimation is proposed, where the data is taken from a sequence of 2D echocardiograms. The method combines the advantages of block-matching and optical flow techniques. The first stage employs a standard block-matching algorithm (sum of absolute differences) to provide a displacement estimate with accuracy of up to one pixel. At the second stage, this estimate is corrected by estimating the parameters of a local image transform within a test window. The parameters of the image transform are estimated in the least-square sense. In order to account for typical heart motions, like contraction/expansion, translation and rotation, a local affine model is assumed within the test window. The accuracy of the new algorithm is evaluated using a sequence of 500 grayscale B-mode images, which are generated as distorted, but known copies of an original ROI, taken from a real echocardiogram. The accuracy of the motion estimation is expressed in terms of errors: maximum absolute error, root-mean-square error, average error and standard deviation. The errors of the proposed algorithm are compared with these of the known block-matching technique with cross-correlation and interpolation in the sub-pixel space. Statistical analysis of the errors shows that the proposed algorithm provides more accurate estimates of the heart motion than the cross-correlation technique with interpolation in the sub-pixel space.

Algorithms↗

PubMed2004

Ultrasound attenuation by encapsulated microbubbles: time and pressure effects.

Ultrasound (US) contrast agents (UCA) consist of artificial encapsulated microbubbles filled with low-diffusivity gas. This study evaluated, both experimentally and theoretically, the behavior of a cloud of encapsulated microbubbles while the surrounding pressure was modified within the physiological range. The theoretical analysis included calculation of US attenuation caused by a bubble cloud. The radius and gas content of each bubble were determined from a solution of a diffusion problem. Shell permeability and rigidity were taken into account. Both experiments and theory demonstrated that, for fixed ambient pressures, higher pressures result in increased rate of attenuation decay. Pulsatile ambient pressure induces pulsations of attenuation of the same frequency. In general, theoretical predictions are in good agreement with experimental data.

Acoustics↗

PubMed2004

Phase unwrapping for 2-D blind deconvolution of ultrasound images.

In most approaches to the problem of two-dimensional homomorphic deconvolution of ultrasound images, the estimation of a corresponding point-spread function (PSF) is necessarily the first stage in the process of image restoration. This estimation is usually performed in the Fourier domain by either successive or simultaneous estimation of the amplitude and phase of the Fourier transform (FT) of the PSE This paper addresses the problem of recovering the FT-phase of the PSF, which is an important reconstruction problem by itself. The purpose of this paper is twofold. First, it provides a theoretical framework, establishing that the FT-phase of the PSF can be effectively estimated by a proper smoothing of the FT-phase of the appropriate radio-frequency (RF) image. Second, it presents a novel approach to the estimation of the FT-phase of the PSF, by solving a continuous Poisson equation over a predefined smooth subspace, in contrast to the discrete Poisson equation solver used for the classical least mean squares phase unwrapping algorithms, followed by a smoothing procedure. The proposed approach is possible due to the distinct properties of the FT-phases, among which the most important property is the availability of precise values of their partial derivatives. This property overcomes the main disadvantage of the discrete schemes, which routinely use wrapped (principal) values of the phase in order to approximate its partial derivatives. Since such an approximation is feasible subject to the restriction that the partial phase differences do not exceed pi in absolute value, the discrete schemes perform satisfactory only for few practical situations. The proposed approach is shown to be independent of this restriction and, thus, it performs for a wider class of the phases with significantly lower errors. The main advantages of the novel method over the algorithms based on discrete schemes are demonstrated in a series of computer simulations and for in vivo measurements.

Algorithms↗

PubMed2003

A new method of spatial compounding imaging.

A new method of spatial compound imaging is presented that improves image quality without the usual requirement to decrease the frame rate. The new method of imaging utilizes three transducers for data acquisition. The transducer located at the center of the transducer system is a phased array probe that acts as both transmitter and receiver. The other transducers are unfocused pistons that act only as receivers. Envelope data acquired by each transducer are combined to form a final image with improved quality (speckle contrast, target detectability and lateral resolution). It is shown that the improvement in speckle contrast depends on the correlation between individual images acquired by the transducers. The effective aperture approach is used for analytic estimation of the correlation between images in order to optimize the lateral separation between transducers. Using simulations, several compounding strategies have been performed to find the strategy that maximizes image quality. The central frequency of 2.5 MHz is used in simulations. Quantitative analysis of simulated B-mode images shows that the new method of imaging efficiently improves visibility, detectability, and lateral resolution of low contrast regions. The image frame rate is preserved because multiple scans are not required for the spatial compounding.

Computer Simulation↗

PubMed2003

A new method of ultrasound color flow mapping.

Conventional ultrasound color flow mapping systems estimate and visualize only the axial velocity component. To obtain the transverse velocity component a modification of a multiple-beam method is proposed. The new two-dimensional color flow mapping system has a small size and consists of three transducers. The central transducer is an appodized and focused phased array. The other transducers are unfocused probes. Three transducers act as receivers and the central transducer operates as a transmitter. All receivers acquire rf scan lines that are then processed to estimate three axial velocity components using an autocorrelation method. These estimates are then combined to estimate the transverse velocity component, taking into account the geometric relationships among three transducers. Two algorithms for transverse velocity estimation are proposed. The first uses the Doppler angle estimate for calculation of the transverse velocity component. The other algorithm calculates the transverse velocity component directly from the axial components. The accuracy of the flow velocity estimators is estimated by simulations. Analysis of accuracy allows choosing the more effective algorithm for two-dimensional velocity estimation, which is insensitive to variations of the Doppler angle.

Algorithms↗

PubMed2003

Robust estimation of ultrasound pulses using outlier-resistant de-noising.

A different approach to the problem of estimation of the ultrasound pulse spectrum, which usually arises as a part of ultrasound image restoration algorithms, is presented. It is shown that this estimation problem can be reformulated in terms of a de-noising problem. In this formulation, the log-spectrum of a radio-frequency line (RF-line) is viewed as a noisy measurement of the signal that needs to be estimated, i.e., the ultrasound pulse log-spectrum. The log-spectrum of the tissue reflectivity function (i.e., tissue response) is considered as the noise to be rejected. The contribution of the paper is twofold. First, it provides statistical description of the reflectivity function log-spectrum for the case, when the samples of the reflectivity function are independent identically distributed (i.i.d.) Gaussian random variables. Moreover, it is shown that the problem of the pulse spectrum recovery is essentially a de-noising problem. Consequently, it is suggested to solve the problem within the framework of the de-noising by wavelet shrinkage. Second, a computationally efficient algorithm is proposed for the pulse-spectrum estimation, which can be viewed as a modified version of the classical Donoho's three-step de-noising procedure. This modification is necessary, because of specific properties of the noise to be rejected. It is shown, that whenever the samples of the reflectivity function can be assumed to be i.i.d. Gaussian random variables, the samples of its log-spectrum obey the Fisher-Tippet distribution. For this type of noise, straightforward implementation of the standard de-noising can cause serious estimation errors. In order to overcome this difficulty, an outlier-resistant de-noising is performed. The unique properties of this modified de-noising algorithm allow estimating the pulse spectrum adaptively to its properties, as they are continuously influenced by the frequency-dependent attenuation process. The performance of the proposed algorithm is examined in a series of computer-simulations. It is shown that this algorithm, developed on the assumption of the "Gaussian" reflectivity function, remains applicable for broader classes of distributions. The results obtained in a series of in vivo experiments reveal superior performance of the novel approach over some of alternative estimation techniques, e.g., cepstrum-based estimation.

Adult↗

PubMed2002

Blind deconvolution of ultrasound sequences using nonparametric local polynomial estimates of the pulse.

The problem of reconstructing the reflectivity of a biological tissue is examined by means of blind deconvolution of the echo ultrasound signals. It is shown that the quality of the reconstruction procedure can be significantly improved when initially the ultrasonic pulse is accurately estimated. A new approach to the estimation of the ultrasound pulse echo sequences is proposed, using local polynomial approximation, which is closely related to the wavelet transform theory. This approach can be viewed as a modification of homomorphic deconvolution, by using bases different from the Fourier basis of the space of square-integrable functions L2. The bases used here are the orthogonal compactly supported wavelet bases. It is shown that the locality of the estimate can be extremely useful in number of cases of practical interest, resulting in estimates with smaller root-mean squared (rms) errors, as compared with estimates employing the Fourier basis. This approach is applied to ultrasound signals, for estimation of the ultrasound pulse log-spectrum from the log-spectrum of radio-frequency (RF) sequences. It is shown, conceptually and experimentally, that the proposed approach can provide robust and rapidly computed estimates of the ultrasound pulses from the RF-sequences, as obtained in the process of tissue scanning. The pulse phase was recovered using the minimum-phase assumption, which was found to hold for the transducers in use. The obtained pulse estimates are used for the deconvolution of the RF-sequences, which result in stable estimates of the tissue reflectivity function, fairly independent of the properties of the imaging system. Simulated data, data obtained from several phantoms and from in vitro experiments have been processed and the results seem to be quite promising.

Animals↗

PubMed2002

Electromagnetic impedance tomography (EMIT): a new method for impedance imaging.

We propose a new impedance imaging method, electromagnetic impedance tomography (EMIT), in which the boundary electric potential measurements in electrical impedance tomography (EIT) are augmented by measurements of the exterior magnetic field induced by the currents excited in the object by the standard EIT procedures. These magnetic measurements can be obtained reliably and inexpensively by simple pickup coils located around the imaged cross section. We derive expressions for the forward problem and for the Jacobian of the measurements, and propose an iterative reconstruction algorithm using a squared error cost function. The performance of EMIT and EIT is compared in numerical simulations using a finite-element model for the conductivity distribution of several phantoms. Evaluation of the rank and condition of the Jacobian demonstrates that the additional magnetic measurements provided by a few pickup coils in EMIT turn an underdetermined EIT problem into a well-posed one with reasonable condition, or significantly improve the conditioning of the EIT problem when it is already fully determined. Reconstructions of various phantoms reveal that EMIT provides particularly significant visual and quantitative improvement (threefold to tenfold reduction in the root-mean-squared error) in the sensitivity at the center of the object, which is the area most difficult to image using EIT.

Computer Simulation↗

PubMed2002

A high-resolution technique for ultrasound harmonic imaging using sparse representations in Gabor frames.

Over the last few decades there were dramatic improvements in ultrasound imaging quality with the utilization of harmonic frequencies induced by both tissue and echo-contrast agents. The advantages of harmonic imaging cause rapid penetration of this modality to diverse clinical uses, among which myocardial perfusion determination seems to be the most important application. In order to effectively employ the information, comprised in the higher harmonics of the received signals, this information should be properly extracted. A commonly used method of harmonics separation is linear filtering. One of its main shortcomings is the inverse relationship between the detectability of the contrast agent and the axial resolution. In this paper, a novel, nonlinear technique is proposed for separating the harmonic components, contained in the received radio-frequency images. It is demonstrated that the harmonic separation can be efficiently performed by means of convex optimization. It performs the separation without affecting the image resolution. The procedure is based on the concepts of sparse signal representation in overcomplete signal bases. A special type of the sparse signal representation, that is especially suitable for the problem at hand, is explicitly described. The ability of the novel technique to acquire "un-masked," second (or higher) harmonic images is demonstrated in series of computer and phantom experiments.

Algorithms↗