Harold B. Levene

Frequency and concentration dependence of the backscatter coefficient of the ultrasound contrast agent Albunex

A broadband ultrasonic measurement system has been utilized to characterize the concentration and frequency dependence of in vitro suspensions of Albunex® microspheres at concentrations ranging from 1.7×105 to 2.1×107 microspheres/mL and over a bandwidth of 1–16 MHz. The apparent backscattered power (not compensated for effects due to attenuation) was shown to increase with dose for lower concentrations of microspheres, but then to decrease rapidly with increasing concentration where attenuation effects become significant. Measurements of signal loss demonstrated that the attenuation grew exponentially with increasing concentration, so that a doubling of the number of microspheres led to a doubling of the value of the attenuation coefficient measured in dB/cm. This relationship was demonstrated over the entire system bandwidth. Compensation of the apparent backscattered power for the attenuation yielded the backscatter transfer function. This quantity was shown to be linearly proportional to concentration...

Quantitative measurements of second harmonic Doppler using ultrasound contrast agents

Quantitative measurements of second harmonic and first harmonic Doppler were carried out using two ultrasound contrast agents, Albunex and FS069. The RMS amplitudes of the Doppler shift spectra were measured as a function of the concentration of the agents, frequency and transmitted acoustic pressure. The results showed that, for a given lot of contrast agent investigated, FS069 was able to produce higher levels of first and, especially, second harmonic signals compared to Albunex. Under the same experimental conditions, the RMS Doppler amplitude (RDA) of FS069 was 3.8 +/- 0.8 dB higher than Albunex at first harmonic and 12.6 +/- 0.8 dB higher at second harmonic. The ratio of the second harmonic to first harmonic RDA, which we called R2/R1, decreases at a rate of 7 dB/MHz for both agents with increasing frequency. The difference in the value of R2/R1 between FS069 and Albunex at any frequency was approximately 4.5 dB. R2/R1 was found to increase linearly as a function of the transmitted acoustic pressure for both agents. Simulations using the Rayleigh-Plesset equation show a decrease of R2/R1 at a rate of 5 dB/MHz. Comparison of experimental results with theory indicates that the shell elasticity parameter may be an increasing function of the mean diameter of the bubbles.

A feasibility study on quantitating myocardial perfusion with Albunex®, an ultrasonic contrast agent

Quantitating regional myocardial perfusion has been the much sought-after but still elusive goal of many intensive investigations over the years. Videodensitometry of the variation of myocardial echogenicity in two-dimensional (2-D) echocardiograms as a function of time in conjunction with the injection of a bolus of an ultrasound contrast agent has been used clinically as a tool for a direct assessment of regional myocardial perfusion, despite that the precise relationship between tissue echogenicity observed on an image and the echoes detected by the ultrasonic probe is unknown. A study was undertaken to determine whether ultrasonic backscatter calculated from unprocessed radio frequency (RF) echoes returned from myocardium could be used to quantitate regional myocardium perfusion. A real-time ultrasonic scanner has been modified and interfaced to a microcomputer to acquire RF data at a rate up to 10 frames per second. Preliminary experimental data were obtained from four open-chest dogs following intracoronary injection of a bolus of Albunex and two dogs following intravenous injection with this modified scanner. On one hand, these results indicate that the integrated backscatter measured from the region of myocardium perfused by the coronary artery where Albunex is injected and selected for monitoring initially increases, reaches a peak, and then decreases as the contrast agent is washed out and that the magnitude of the peak is approximately linearly proportional to the volume concentration of Albunex microspheres injected, clearly demonstrating the feasibility of this approach for quantitating region myocardial perfusion. On the other hand, intravenous injections did not result in any appreciable change in myocardial backscatter in the left ventricle although a response could be observed in the left ventricular blood pool.

Some considerations on the measurements of mean frequency shift and integrated backscatter following administration of albunex

Ultrasonic contrast agents have been of heightened interest in recent years. More success has been achieved by agents consisting of micro bubbles, since only a few of these agents are capable of producing very strong ultrasonic backscattered signals for the enhancement of certain tissue structures. Recent investigations also demonstrate that an analysis of the radio frequency (RF) backscattered echoes by the contrast agents may lead to quantitative means for assessing tissue perfusion. In these studies, a parameter, mean frequency shift (MFS) of the RF signal, along with integrated backscatter (IB) has received the most attention. In an effort to better understand the physical mechanisms responsible for the observed mean frequency shift, we have performed experiments on 10 dogs following injections of Albunex (Molecular Biosystems, Inc.) into the left atrium, coronary artery and abdominal aorta, respectively, for investigations in the heart and kidney. The integrated backscatter and mean frequency (MF) of a region of interest (ROI) were calculated from the RF signal acquired with a modified real-time ultrasonic scanner. The results show consistently that the RF signals acquired from all regions of interest are greatly affected by the presence of the contrast agent in the path between the transducer and the ROI, which can cause either an upward or a downward shift of the MF. This could not be observed by video densitometry or a measurement of the IB alone. The MFS is the result of the resonant behavior of the micro bubbles, which is related to the frequency, ambient pressure, and physical properties of the bubbles including size distribution, surface tension and concentration. On the other hand, when there is no contrast agent present in the path, a downward frequency shift is seen.

Characterization of Albunex

Albunex® is an ultrasound contrast agent prepared by sonicating 5% human serum albumin to produce stable, air‐filled, albumin microspheres. It is an effective ultrasound contrast agent for use with echocardiography and other ultrasound radiology procedures. The characteristics of Albunex that are responsible for the clinically observed high echogenicity of Albunex are discussed. Albunex is composed of a high concentration of noncoalescing microspheres (400–500 μ/nl) with a mean diameter of ≈4 μm and a shell thickness of 30–50 nm, as determined by particle analysis, light microscopy, and electron microscopy. Attenuation and backscatter measurements as a function of ultrasonic frequency and amplitude are reported for varying concentration and size distributions of Albunex.

Recent theoretical and experimental results with AlbunexR, a contrast agent for diagnostic ultrasonography

AlbunexR is an ultrasound contrast agent prepared by sonicating 5% human serum albumin to produce stable, air‐filled, albumin‐coated microspheres. It is an effective ultrasound contrast agent for use during echocardiography and other ultrasound radiological procedures. Current research is directed toward understanding the physics of the interaction of ultrasound with AlbunexR in tissue. A theoretical model describing the dynamics of these bubbles has been developed by assuming a solid elastic shell. The shell (1) supports a strain that counters the effect of surface tension and thus stabilizes the bubble against dissolution; (2) increases the stiffness of the bubble and thus raises the resonance frequency of the bubble significantly; (3) increases the effective damping of the bubble and thus reduces the scattering cross section of the bubble markedly. Experimental measurements of speed of sound, attenuation coefficient, and backscatter coefficient have been made as functions of acoustic frequency and gas ...