Modeling of nonlinear viscous stress in encapsulating shells of lipid-coated contrast agent microbubbles

A general theoretical approach to the development of zero-thickness encapsulation models for contrast microbubbles is proposed. The approach describes a procedure that allows one to recast available rheological laws from the bulk form to a surface form which is used in a modified Rayleigh-Plesset equation governing the radial dynamics of a contrast microbubble. By the use of the proposed procedure, the testing of different rheological laws for encapsulation can be carried out. Challenges of existing shell models for lipid-encapsulated microbubbles, such as the dependence of shell parameters on the initial bubble radius and the “compression-only” behavior, are discussed. Analysis of the rheological behavior of lipid encapsulation is made by using experimental radius-time curves for lipid-coated microbubbles with radii in the range 1.2-2.5 μm. The curves were acquired for a research phospholipid-coated contrast agent insonified with a 20 cycle, 3.0 MHz, 100 kPa acoustic pulse. The fitting of the experimental data by a model which treats the shell as a viscoelastic solid gives the values of the shell surface viscosity increasing from 0.30 × 10⁻⁸ kg/s to 2.63 × 10⁻⁸ kg/s for the range of bubble radii, indicated above. The shell surface elastic modulus increases from 0.054 N/m to 0.37 N/m. It is proposed that this increase may be a result of the lipid coating possessing the properties of both a shear-thinning and a strain-softening material. We hypothesize that these complicated rheological properties do not allow the existing shell models to satisfactorily describe the dynamics of lipid encapsulation. In the existing shell models, the viscous and the elastic shell terms have the linear form which assumes that the viscous and the elastic stresses acting inside the lipid shell are proportional to the shell shear rate and the shell strain, respectively, with constant coefficients of proportionality. The analysis performed in the present paper suggests that a more general, nonlinear theory may be more appropriate. It is shown that the use of the nonlinear theory for shell viscosity allows one to model the “compression-only” behavior. As an example, the results of the simulation for a 2.03 μm radius bubble insonified with a 6 cycle, 1.8 MHz, 100 kPa acoustic pulse are given. These parameters correspond to the acoustic conditions under which the “compression-only” behavior was observed by de Jong et al. [Ultrasound Med. Biol. 33 (2007) 653-656]. It is also shown that the use of the Cross law for the modeling of the shear-thinning behavior of shell viscosity reduces the variance of experimentally estimated values of the shell viscosity and its dependence on the initial bubble radius.     

Resonance frequencies of lipid-shelled microbubbles in the regime of nonlinear oscillations

Knowledge of resonant frequencies of contrast microbubbles is important for the optimization of ultrasound contrast imaging and therapeutic techniques. To date, however, there are estimates of resonance frequencies of contrast microbubbles only for the regime of linear oscillation. The present paper proposes an approach for evaluating resonance frequencies of contrast agent microbubbles in the regime of nonlinear oscillation. The approach is based on the calculation of the time-averaged oscillation power of the radial bubble oscillation. The proposed procedure was verified for free bubbles in the frequency range 1-4 MHz and then applied to lipid-shelled microbubbles insonified with a single 20-cycle acoustic pulse at two values of the acoustic pressure amplitude, 100 kPa and 200 kPa, and at four frequencies: 1.5, 2.0, 2.5, and 3.0 MHz. It is shown that, as the acoustic pressure amplitude is increased, the resonance frequency of a lipid-shelled microbubble tends to decrease in comparison with its linear resonance frequency. Analysis of existing shell models reveals that models that treat the lipid shell as a linear viscoelastic solid appear may be challenged to provide the observed tendency in the behavior of the resonance frequency at increasing acoustic pressure. The conclusion is drawn that the further development of shell models could be improved by the consideration of nonlinear rheological laws.     

Ultrasound Attenuation in Biological Tissue Predicted by the Modified Doublet Mechanics Model

Experimental results have shown that in the megahertz frequency range the relationship between the acoustic attenuation coefficient in soft tissues and frequency is nearly linear. The classical continuum mechanics （CCM）, which assumes that the materiaJ is uniform and continuous, faJls to explain this relationship particularly in the high megahertz range. Doublet mechanics （DM） is a new elastic theory which takes the discrete nature of material into account. The current DM theory however does not consider the loss. We revise the doublet mechanics （DM） theory by including the loss term, and cMculate the attenuation of a soft tissue as a function of frequency using the modified the DM theory （MDM）. The MDM can now well explain the nearly linear relationship between the acoustic attenuation coefficient in soft tissues and frequency.     

Modeling of the acoustic response from contrast agent microbubbles near a rigid wall

In ultrasonic targeted imaging, specially designed encapsulated microbubbles are used, which are capable of selectively adhering to the target site in the body. A challenging problem is to distinguish the echoes from such adherent agents from echoes produced by freely circulating agents. In the present paper, an equation of radial oscillation for an encapsulated bubble near a plane rigid wall is derived. The equation is then used to simulate the echo from a layer of contrast agents localized on a wall. The echo spectrum of adherent microbubbles is compared to that of free, randomly distributed microbubbles inside a vessel, in order to examine differences between the acoustic responses of free and adherent agents. It is shown that the fundamental spectral component of adherent bubbles is perceptibly stronger than that of free bubbles. This increase is accounted for by a more coherent summation of echoes from adherent agents and the acoustic interaction between the agents and the wall. For cases tested, the increase of the fundamental component caused by the above two effects is on the order of 8-9 dB. Bubble aggregates, which are observed experimentally to form near a wall due to secondary Bjerknes forces, increase the intensity of the fundamental component only if they are formed by bubbles whose radii are well below the resonant radius. If the formation of aggregates contributes to the growth of the fundamental component, the increase can exceed 17 dB. Statistical analysis for the comparison between adhering and free bubbles, performed over random space bubble distributions, gives p-values much smaller than 0.05.     

Feasibility of using ultrasound contrast agents to increase the size of thermal lesions induced by non-focused transducers: in vitro demonstration in tissue mimicking phantom

Miniature flat ultrasound transducers have shown to be effective for a large variety of thermal therapies, but the associated superficial heating implicates developing original strategies in order to extend therapeutic depth. The goal of the present paper is to use ultrasound contrast agents (UCA) to increase remote attenuation and heating. Theoretical simulations demonstrated that increasing attenuation from 0.27 to 0.8 Np/cm at 10 MHz beyond a distance of 18 mm from the transducer should result in longer thermal damages due to protein coagulation in a tissue mimicking phantom. Contrast agents (BR14, Bracco, Plan-les-Ouates, Switzerland) were embedded in thermo-sensitive gel and attenuations ranging from 0.27 to 1.33 Np/cm were measured at 10 MHz for concentrations of BR14 between 0 and 4.8%. Thermal damages were then induced in several gels, which had different layering configurations. Thermal damages, 12.8 mm in length, were obtained in homogeneous gels. When mixing contrast agents at a concentration of 3.2% beyond a first 18 mm-thick layer of homogeneous gel, the thermal damages reached 21.5 mm in length. This work demonstrated that contrast agents can be used for increasing attenuation remotely and extending therapeutic depth induced by a non-focused transducer. Additional work must be done in vivo in order to verify the remote-only distribution of bubbles and associated increase in attenuation.     

Directing ultrasound at the cemento-enamel junction (CEJ) of human teeth: I. Asymmetry of ultrasonic path lengths

The diagnosis of degenerative changes in human teeth is of general interest because early detections can avoid greater health problems and further weakening effects. Since the wear of teeth determines their stability and lifetime in relation to the physiological load, an ultrasonic survey of any dimensional changes of the enamel layer and especially of the dentin wall thickness may be very helpful. However, an ultrasonographic diagnosis requires first to determine the anisotropic human tooth properties at clinically relevant locations and to simulate wave propagation phenomena in inhomogeneous tooth models with proper dimensions. The first article of a series that provides modular data of mineralized tissues in human teeth at the cemento-enamel junction (CEJ) deals with an ultrasonic method for measuring the asymmetry of dimensional characteristics of extracted human teeth and their ultrasonic path lengths (UPL). Heavily attenuating tooth halves were investigated with respect to the symmetry of normal and inclined oppositely directed radial ultrasonic paths. The measured UPLs ranged from 1.2 mm to 4.4 mm. The relative difference in inclined UPLs between the left and the right tooth halves reaches almost 30%. This reveals a large asymmetry. The mean difference of angles that represent fastest path lengths was 2.2+/-8.1 degrees, which indicates large asymmetry and anisotropy. Several aspects, which are required for a proper integration of asymmetric data into models designed for medical element engineering and simulation (MEES), are discussed.     

Parameter studies in practical nitrogen CARS thermometry using standard and advanced fitting codes

A systematic study of the influence of the collisional narrowing and the cross coherence effect on the temperature analysis of N₂-Q branch-CARS spectra at atmospheric pressure is presented. A comparison of calculated spectra over a temperature range 300–2000 K reveals that the standard theory neglecting these effects leads to temperature errors of +1.7% under flame conditions, when the nonresonant background is suppressed. This result is supported by the analysis of experimental CARS temperature measurements on a standard laminar diffusion flame. Furthermore, the temperature misreadings originating from erroneous slit function parameters and laser linewidth were investigated.     

Optical emission spectroscopic studies on laser ablated TiO2 plasma

Optical emission spectroscopic investigations of the plasma produced during Nd:YAG laser ablation of sintered TiO₂ targets, in oxygen and argon gas environments are reported. The spatial variations of electron temperature (T_e) and electron number density (N_e) are studied. The effect of oxygen/argon pressure on electron temperature (T_e) and electron number density (N_e) is presented. The kinematics of the emitted particles and expansion of plume edge are discussed. Spatio-temporal variations of various species in TiO₂ plasma were recorded and corresponding velocities were calculated. The effect of oxygen pressure on intensity of neutral/ion species and their corresponding velocities is also reported.     

Acoustic scattering of a high-order Bessel beam by an elastic sphere

The exact analytical solution for the scattering of a generalized (or “hollow”) acoustic Bessel beam in water by an elastic sphere centered on the beam is presented. The far-field acoustic scattering field is expressed as a partial wave series involving the scattering angle relative to the beam axis and the half-conical angle of the wave vector components of the generalized Bessel beam. The sphere is assumed to have isotropic elastic material properties so that the nth partial wave amplitude for plane wave scattering is proportional to a known partial-wave coefficient. The transverse acoustic scattering field is investigated versus the dimensionless parameter ka(k is the wave vector, a radius of the sphere) as well as the polar angle θ for a specific dimensionless frequency and half-cone angle β. For higher-order generalized beams, the acoustic scattering vanishes in the backward (θ = π) and forward (θ = 0) directions along the beam axis. Moreover it is possible to suppress the excitation of certain resonances of an elastic sphere by appropriate selection of the generalized Bessel beam parameters.     

A performance analysis of echographic ultrasonic techniques for non-invasive temperature estimation in hyperthermia range using phantoms with scatterers

Optimization of efficiency in hyperthermia requires a precise and non-invasive estimation of internal distribution of temperature. Although there are several research trends for ultrasonic temperature estimation, efficient equipments for its use in the clinical practice are not still available. The main objective of this work was to research about the limitations and potential improvements of previously reported signal processing options in order to identify research efforts to facilitate their future clinical use as a thermal estimator.In this document, we have a critical analysis of potential performance of previous ultrasonic research trends for temperature estimation inside materials, using different processing techniques proposed in frequency, time and phase domains. It was carried out in phantom with scatterers, assessing at their specific applicability, linearity and limitations in hyperthermia range. Three complementary evaluation indexes: technique robustness, Mat-lab processing time and temperature resolution, with specific application protocols, were defined and employed for a comparative quantification of the behavior of the techniques. The average increment per °C and mm was identified for each technique (3 KHz/°C in the frequency analysis, 0.02 rad/°C in the phase domain, while increments in the time domain of only 1.6 ns/°C were found). Their linearity with temperature rising was measured using linear and quadratic regressions and they were correlated with the obtained data.New improvements in time and frequency signal processing in order to reveal the potential thermal and spatial resolutions of these techniques are proposed and their subsequent improved estimation results are shown for simulated and measured A-scans registers. As an example of these processing novelties, an excellent potential resolution of 0.12 °C into hyperthermia range, with near-to-linear frequency dependence, could be achieved.Specifically defined “numerical” and physical multi-scatter phantoms are described, which mimic ultrasound velocity in tissues of about 1560 m/s @ 35 °C and have a quasi-uniform internal scattering structure designed to assure standard signal patterns adequate for processing comparisons in the same time and sound velocity conditions for all the techniques analyzed, and to obtain easily repeatable multi-pulse echo-patterns.A perfect lineal dependence (100% of correlation coefficient) between the unitary average increment measured by each technique and temperature rising was observed while working with simulated A-scan registers, where all the parameters are under an accurate control. Nevertheless a very small quadratic tendency appeared in the results obtained from experimental echo registers, which are more similar to a real tissues case. It would be an interesting future work to analyze the behavior of these techniques in real tissues in order to confirm or reject this light quadratic tendency.Finally, new methods were detailed and applied in order to precisely quantify the advantages of each estimation technique; their respective intrinsic limitations were also underlined.     

Optimally discriminant moments for speckle detection in real B-scan images

The paper presents and evaluates a speckle detection method for B-scan images. This is a fully automatic method and does not require information about the sensor parameters, which is often missing in retrospective studies.The characterization and posterior detection of speckle noise in ultrasound (US) has been regarded as an important research topic in US imaging, for improving signal-to-noise ratio by removing speckle noise and for exploiting speckle correlation information. Most of the existing methods require either manual intervention, the need to know sensor parameters or are based on statistical models which often do not generalize well to B-scans of different imaging areas. The proposed method aims to overcome those limitations.The main novelty of this work is to show that speckle detection can be improved based on finding optimally discriminant low order speckle statistics. In addition, and in contrast with other approaches the presented method is fully automatic and can be efficiently implemented to B-scan images.The method detects speckle patches using an ellipsoid discriminant function which classifies patches based on features extracted from optimally discriminant low order moments of the uncompressed intensity B-scan information. In addition, if the uncompressed signal is not available, we propose and evaluate a method for the estimation of this factor.The computation of low order moments using an optimality criteria, the decompression factor estimation and other key aspects of the method are quantitatively evaluated using both simulated and real (phantom and in vivo) data. Speckle detection results are obtained using again phantom and in vivo studies which show the validity of our approach. In addition, speckle probability images (SPI) are presented which provide valuable information about the distribution of speckle and non-speckle areas in an image.The presented evaluation and results show the effectiveness of our approach. In particular, the need for using discriminant analysis to determine the optimal discriminant power of the statistical moments and that this optimal value strongly depends on the characteristics and imaged tissues in the B-scan data.     

Air-coupled ultrasound stimulated optical vibrometry for resonance analysis of rubber tubes

Air-coupled ultrasound stimulated optical vibrometry is proposed to generate and detect the resonances of a rubber tube in air. Amplitude-modulated (AM) focused ultrasound radiation force from a broadband air-coupled ultrasound transducer with center frequency of 500 kHz is used to generate a low frequency vibration in the tube. The resonances of several modes of the tube are measured with a laser vibrometer of 633 nm wavelength. A wave propagation approach is used to calculate the resonances of the tube from its known material properties. Theoretical and experimental resonance frequencies agree within 5%. This method may be useful in measuring the in vitro elastic properties of arteries from the resonance measurements in air. It may also be helpful to better understand the coupling effects of the surrounding tissue and interior blood on the vessel wall by measuring the resonance of the vessel in vitro and in vivo.     

Estimation of critical and viscous frequencies for Biot theory in cancellous bone

The use of Biot theory for modelling ultrasonic wave propagation in porous media involves the definition of a "critical frequency" above which both fast and slow compressional waves will, in principle, propagate. Critical frequencies have been evaluated for healthy and osteoporotic cancellous bone filled with water or marrow, using data from the literature. The range of pore sizes in bone gives rise to a critical frequency band rather than a single critical frequency, the mean of which is lower for osteoporotic bone than normal bone. However, the critical frequency is a theoretical concept and previous researchers considered a more realistic "viscous frequency" above which both fast and slow waves may be experimentally observed. Viscous frequencies in bone are found to be several orders of magnitude greater than calculated critical frequencies. Whereas two waves may well be observed at all ultrasonic frequencies for water-filled cancellous bone at 20 degrees C, it is probable megahertz frequencies would be needed for observation of two waves in vivo.     

High-speed observation of cavitation bubble clouds near a tissue boundary in high-intensity focused ultrasound fields

Cavitation bubble clouds generated near a tissue boundary by high-intensity focused ultrasound (HIFU) were studied using high-speed photography. In all, 171 image series were captured during the initial 100 ms of continuous HIFU exposure, which showed that cavitation bubble clouds at the tissue boundary organized into two structures - “cone-shape bubble cloud structure” recorded in 146 image series and “crown-shape bubble cloud structure” recorded in 18 image series. The remaining 7 image series showed the interchanging of these two structures. It was found that when cavitation bubbles first appeared at the tissue boundary, they developed to cone-shape bubble cloud. The cone-shape bubble cloud structure was characterized by a nearly fixed tip in front of the tissue boundary. When the cavitation bubbles initially appeared away from the tissue boundary they evolved into a crown-shape bubble cloud. Deformation of tissue boundary was shown in all the recorded image series.     

Quantum-mechanical vs. semi-classical spectral-line widths and shifts from the line core in the non-impact region for the Ar-perturbed/ K-radiator system

New quantum-mechanical (QM) and semi-classical (SC) shifts (d's) and widths (HWHM's, w's) were measured from the line core of computed full spectral-line shapes for the Ar-perturbed/K-radiator system (K/Ar). The initial state of our model was based on a 4p²P_3/2,1/2 pseudo-potential for the K/Ar system, and the final state on a zero potential. The Fourier transform of the line shape formed the basis for the computations. Excellent agreement was found between the QM and SC values of d and of w in a high-pressure (P) non-impact region, which was characterized by a √P dependence of w and a P dependence of d. These agreements were shown to be another example of a correspondence between classical (SC) quantities and QM quantities in the limit of large quantum numbers. Typically at P=1×10⁶ Torr and T=400 K, w_QM=448 cm⁻¹ and w_SC=479 cm⁻¹, where the deviation from the mean is ±3.3%. Also, d_QM=−3815 cm⁻¹ and d_SC=−3716 cm⁻¹, where the deviation from the mean is ±1.3%. A new general method was formulated which yielded a definite pressure P₀, which was defined as an upper limit to the low-pressure impact approximation and a lower limit to the non-impact region.     

Sensitivity to point-spread function parameters in medical ultrasound image deconvolution

Clinical ultrasound images are often perceived as difficult to interpret due to image blurring and speckle inherent in the ultrasound imaging. But the image quality can be improved by deconvolution using an estimate of the point-spread function. However, it is difficult to obtain a sufficiently accurate estimate of the point-spread function in vivo because of the unknown properties of the soft tissue in clinical applications. Local variations in the speed of sound and attenuation change the pulse and beam shape. These in turn affect the point-spread function. The purpose and novelty of this paper is therefore to explore the sensitivity of a state-of-the-art deconvolution algorithm to uncertainty in the point-spread function. The point-spread function in our restoration algorithm is made shift invariant in the lateral dimension but shift dependent in the axial direction, and is modelled to match a 128-element 1D linear array often found in clinical use. We present simulated and in vitro sensitivity analyses of two-dimensional deconvolution while varying six parameters on which the point-spread function depends. Uncertainty in the ultrasound machine is analysed by varying the axial depths of lateral and elevational foci alongside height and width of transducer elements. Sensitivity to tissue influence is investigated by varying the speed of sound and frequency-dependent attenuation of the electro-mechanical impulse response. The results are analysed both quantitatively and in terms of the perceived image quality. First, the assessment of deconvolution using the logarithmic image amplitude is found to be a better indicator of the perceived improvement in the restoration. Secondly, the two most critical parameters for two-dimensional deconvolution are discovered to be the lateral focus and the speed of sound, because the success of deconvolution is perceived primarily in terms of deblurring. We also observed similar patterns for the simulation and in vitro experiment. Finally, we show that it is possible to restore in vivo ultrasound images using an assumed point-spread function and hence conclude that an exact point-spread function is not necessary for enhancing ultrasound image quality by deconvolution.     

Optical studies of atoms and ions in superfluid helium using a ccd-camera system

The spectroscopic study ions and atoms immersed into liquid helium can contribute to the understanding of the structure of pointlike defects in helium and their interaction with the superfluid phase as well. Ions and atoms serve as microprobes in the form of so calledbubble orsnowball type defects in the quantum fluid. The optical emission of these structures is recorded. From the optical spectra of previous experiments the influence of the surrounding helium on the electronic configuration of the impurity atoms or ions was examined. In this experiment the light emitted from the defect atoms is observed by a camera. The pictures obtained yield information about the distribution and the motion of the defect particles in the superfluid. As an example the fluorescence light resulting from the recombination of magnesium, barium and thallium ions with excess electrons in superfluid helium was recorded.     

Group velocity, phase velocity, and dispersion in human calcaneus in vivo

Commercial bone sonometers measure broadband ultrasonic attenuation and/or speed of sound (SOS) in order to assess bone status. Phase velocity, which is usually measured in frequency domain, is a fundamental material property of bone that is related to SOS, which is usually measured in time domain. Four previous in vitro studies indicate that phase velocity in human cancellous bone decreases with frequency (i.e., negative dispersion). In order to investigate frequency-dependent phase velocity in vivo, through-transmission measurements were performed in 73 women using a GE Lunar Achilles Insight commercial bone sonometer. Average phase velocity at 500 kHz was 1489 +/- 55 m/s (mean +/- standard deviation). Average dispersion rate was -59 +/- 52 m/sMHz. Group velocity was usually lower than phase velocity, as is expected for negatively dispersive media. Using a stratified model to represent cancellous bone, the reductions in phase velocity and dispersion rate in vivo as opposed to in vitro can be explained by (1) the presence of marrow instead of water as a fluid filler, and (2) the decreased porosity of bones of living (compared with deceased) subjects.     

In vivo 1H spectroscopic studies of human gastrocnemius muscle at 1.5 T

In vivo high resolution 1H magnetic resonance spectra are observed from the gastrocnemius muscle in 12 normal volunteers. The gross spectral features do not appear to significantly change from individual to individual. However, the number and the relative amplitudes of the resonances from the fatty acid chains are found to exhibit significant variation from normal to normal. The spectra observed on different occasions in the same individual exhibit very little variation. Our studies indicate that it is preferable to use the spin echo sequence with a long echo time to observe water-suppressed proton spectra from the muscle tissue.     

Mesons in the Constituent Quark Model

The quark-antiquark （q^-q） spectrum is studied by solving the Schrōdinger equation in the framework of nonrelativistic constituent quark model. An overall good fit to the experimental data of meson is obtained. The interactions between quark and antiquark consist of quadratic colour confinement-exchange, one-gluon-exchange, and Goldstone-boson-exchange potentials.