Acoustic properties of ultrasound contrast agents

Safety of contrast agents is reported in the years after. Both the intracoronary use of sonicated Renografin as well as intravenous use of commercial product as Albunex and Lechovist has been investigated. Thereafter more pathophysiologic studies were performed. Ten Cate described the possibilities to determine the stenosis of the left anterior descending coronary artery by the contrast outwash in the interventricular septum and Cornel who incidentally reported the Thebesian vein outflow in humans visualised by echo contrast. Cheiriff and his group described myocardial perfusion studies to determine coronary flow reserve before and after Percutaneous Transluminal coronary angioplasty (PTCA). Coronary collateral perfusion after myocardial infarction or PTCA can be assessed. Also, successful thrombolysis, resulting in a patent coronary artery, is often not accompanied by a return of normal perfusion or wall motionUltrasound contrast agents have been used in the medical diagnostic field for a number of years and for very different purposes. These agents have been employed when echo images proved inadequate or when further information about the blood flow was required. Originally, contrast agents were home-made, being produced simply by passing saline through a

Optical observations of acoustical radiation force effects on individual air bubbles

Previous studies dealing with contrast agent microbubbles have demonstrated that ultrasound (US) can significantly influence the movement of microbubbles. In this paper, we investigated the influence of the acoustic radiation force on individual air bubbles using high-speed photography. We emphasize the effects of the US parameters (pulse length, acoustic pressure) on different bubble\ud patterns and their consequences on the translational motion of the bubbles. A stream of uniform air bubbles with diameter ranging from 35 um to 79 um was generated and insonified with a single US pulse emitted at a frequency of 130 kHz. The bubble sizes have been chosen to be above, below, and at resonance. The peak acoustic pressures used in these experiments ranged from 40 kPa to 120 kPa. The axial displacements of the bubbles produced by the action of the US pulse were optically recorded using a high-speed camera at 1 kHz frame rate. The experimental results were compared to a simplified force balance theoretical model, including the action of the primary radiation force and the fluid drag force. Although the model is quite simple and does not take into account phenomena like bubble shape oscillations and added mass, the experimental findings agree with the predictions. The measured axial displacement increases quasilinearly with the burst length and the transmitted acoustic pressure. The axial displacement varies with the size and the density of the air bubbles, reaching a maximum at the resonance size of 48 um. The predicted displacement values differ by 15% from the measured data, except for resonant bubbles for which the displacement was overestimated by about 40%. This study demonstrates that even a single US pulse produces radiation forces that are strong enough to affect the bubble position

Acoustic modeling of shell-encapsulated gas bubbles

Existing theoretical models do not adequately describe the scatter and attenuation properties of the ultrasound contrast agents Quantison(TM) and Myomap(TM). An adapted version of the Rayleigh-Plesset equation, in which the shell is described by a viscoelastic solid, is proposed and validated for these agents and Albunex(®). The acoustic transmission and scattering are measured in the frequency band from 1-10 MHz. The measured transmission is used to estimate two parameters, the effective bulk modulus, K(eff) describing the elasticity, and the friction parameter, S(F), describing the viscosity of the shell. For the scattering, the difference between measurements and calculations is < 3 dB. For Quantison(TM), the effective bulk modulus is independent of the bubble diameter. For Albunex(®), it increases for decreasing bubble diameter. The nonlinear response of Quantison(TM) is minimal for acoustic pressures up to 200 kPa. For acoustic pressures above 200 kPa, the measured scattering abruptly increases. This increase reaches a level of 20 dB for an acoustic pressure of 1.8 MPa. This response cannot be predicted by the theoretical model developed in this article.Existing theoretical models do not adequately describe the scatter and attenuation properties of the ultrasound contrast agents QuantisonTM and MyomapTM. An adapted version of the Rayleigh-Plesset equation, in which the shell is described by a viscoelastic solid, is proposed and validated for these agents and Albunex. The acoustic transmission and scattering are measured in the frequency band from 1-10 MHz. The measured transmission is used to estimate two parameters, the effective bulk modulus, Keff, describing the elasticity, and the friction parameter, SF, describing the viscosity of the shell. For the scattering, the difference between measurements and calculations is <3 dB. For QuantisonTM, the effective bulk modulus is independent of the bubble diameter. For Albunex, it increases for decreasing bubble diameter. The nonlinear response of QuantisonTM is minimal for acoustic pressures up to 200 kPa. For acoustic pressures above 200 kPa, the measured scattering abruptly increases. This increase reaches a level of 20 dB for an acoustic pressure of 1.8 MPa. This response cannot be predicted by the theoretical model developed in this article

Harmonic chirp imaging method for ultrasound contrast agent

Coded excitation is currently used in medical ultrasound to increase signal-to-noise ratio (SNR) and penetration depth. We propose a chirp excitation method\ud for contrast agents using the second harmonic component of the response. This method is based on a compression filter that selectively compresses and extracts the second harmonic component from the received echo signal. Simulations have shown a clear increase in response for chirp excitation\ud over pulse excitation with the same peak amplitude. This was confirmed by two-dimensional (2-D) optical observations of bubble response with a fast framing camera. To evaluate the harmonic compression method, we applied it to\ud simulated bubble echoes, to measured propagation harmonics, and to B-mode scans of a flow phantom and compared it to regular pulse excitation imaging. An increase of approximately 10 dB in SNR was found for chirp excitation. The\ud compression method was found to perform well in terms of resolution. Axial resolution was in all cases within 10% of the axial resolution from pulse excitation. Range side-lobe levels were 30 dB below the main lobe for the simulated bubble echoes and measured propagation harmonics. However,\ud side-lobes were visible in the B-mode contrast images

A new multifrequency transducer for microemboli detection and classification

The classification of circulating microemboli as gaseous or particulate matter is essential to establish the relevance of detected embolic signals. Transcranial Doppler (TCD) technology has not yet fully succeeded in characterizing the composition of microemboli unambiguously. Recently, the authors proposed a new approach to detect, characterize and size gaseous emboli. The method is based on the nonlinear properties of gaseous bubbles. The application of this approach requires a dedicated transducer with the ability to transmit the adequate frequencies and simultaneously receive the high frequency scattered nonlinear components. The paper presents a multifrequency emboli transducer composed of two independent transmitting elements and a separate receiving part. The transmitting part can cover a frequency band between 100 kHz and 600 kHz. The reception of the signal is performed by a 110 /spl mu/m PVDF layer sensitive over a frequency band ranging from 50 kHz to 2 MHz. Experimental results show that a specific range of gaseous embolus size was detected by each transmitting element. Using the 130 kHz outer element in transmission, microemboli between 35 /spl mu/m and 105 /spl mu/m can be discriminated through their second harmonic or subharmonic emissions while gaseous microemboli between 10 /spl mu/m and 40 /spl mu/m were accurately classified using the 360 kHz inner element. The in vitro results demonstrate that nonlinear properties of microemboli combined with the new transducer offer a real opportunity to characterize and size microemboli

Air bubble in an ultrasound field:theoretical and optical results

The radial motion of a gas bubble has been widely investigated in various studies using different theoretical models. The aim of this study is to compare, qualitatively and quantitatively, the results obtained by optical recording with those of a theoretical model. Bubble oscillations were optically recorded using an ultrafast digital camera, Brandaris. The radius-time, R(t), curves are directly computed from 128 video frames. The resting diameters of the air bubbles were 26-100 /spl mu/m. The ultrasound field was defined as an 8 cycle pulse at a frequency of 130 kHz generating an acoustic pressure of 10-150 kPa. The time and the frequency response of the bubble radial motion were compared to the Keller model. From the results, it is concluded that the Keller model can be used to accurately predict the fundamental and harmonic behavior of gas bubbles

Remote manipulation of cells with ultrasound and microbubbles

Ultrasound in combination with contrast microbubbles has been shown to alter the permeability of cell membranes. This permeabilization feature is used to design new drug delivery systems using ultrasound and contrast agents. Although the exact underlying mechanisms are still unknown, one hypothesis is that oscillating microbubbles cause cell deformation resulting in enhanced cell membrane permeability. In this paper we show the actions of oscillating microbubbles on cultured cells under a microscope recorded with a fast framing camera at 10 million frames per second. Optical observations of microbubbles and cultured cells is possible through the use of a microscope mounted in front of the fast framing camera Brandaris128. The Brandaris128 is capable of recording a sequence of 128 images with a frame rate up to 25 million frames per second. Pig aorta endothelial cells were grown on the inside of an Opticell/spl trade/ container. A diluted suspension of experimental agents BR14 (Bracco Research, Geneva, Switzerland) was added. Ultrasound exposure consisted of one burst of 6 cycles at a frequency of 1 MHz and a P/spl I.bar/ of 0.5 MPa. During ultrasound transmission, the interactions between BR14 microbubbles and cultured cells were recorded using a frame rate of 10 million frames per second. Cell deformation as a result of vibrating microbubbles is studied. Cell deformation is quantified through measuring the displacement of the cells. Microbubble vibration is quantified by measuring its initial, maximal, and minimal radii. We observed that upon ultrasound arrival and microbubble oscillations, the cell membrane deforms up to a few micrometers in length as a result of the oscillation of the microbubble. The membrane deformation rate changes with the oscillation strength of the microbubble. During the sonication, changes in the cross-sectional distance of the cultured cells were observed due to microbubble vibrations. Depending on the maximal vibrations of the microbubble and the distance between the microbubble and the cell, the displacement of the cells varied form 0 to 20% of the cell size. This study reveals the action of oscillating microbubbles on cells. It is known that living cells sense mechanical forces thus there is no doubt that perturbation of the oscillating microbubbles results in profound alterations in the cellular content. This study is the beginning of revealing the functional relationships that lie beyond the remote manipulation of cells and ultrasound microbubble induced permeabilization of the cell membrane

Corrigendum to "In vivo characterization of ultrasound contrast agents: microbubble spectroscopy in a chicken embryo" (Ultrasound Med Biol 2012;38:1608-1617)

The authors regret that there was a mistake in reporting the mol% of the microbubble coating composition used. For all experiments, the unit in mg/mL was utilized, and the conversion mistake occurred only when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Shen et al. 2008; Kilic and Bolukcu 2018), not 328.53 g/mol. On page 1610, the sentence should read “The coating was composed of DSPC (84.8 mol%; P6517, Sigma-Aldrich, Zwijndrecht, The Netherlands); PEG-40 stearate (8.2 mol%; P3440, Sigma-Aldrich); DSPE-PEG(2000) (5.9 mol%; 880125P, Avanti Polar Lipids, Alabaster, AL, USA); and DSPE-PEG(2000)-biotin (1.1 mol%; 880129C, Avanti Polar Lipids).” This correction does not change the conclusions published in this work. The authors apologize for any inconvenience caused