Changes in the echoes from ultrasonic contrast agents with imaging parameters.

Current harmonic imaging scanners transmit a narrowband signal that limits spatial resolution in order to differentiate the echoes from tissue from the echoes from microbubbles. Because spatial resolution is particularly important in applications, including mapping vessel density in tumors, we explore the use of wideband signals in contrast imaging. It is first demonstrated that microspheres can be destroyed using one or two pulses of ultrasound.

Optical and acoustical observations of the effects of ultrasound on contrast agents.

Optimal use of encapsulated microbubbles for ultrasound contrast agents and drug delivery requires an understanding of the complex set of phenomena that affect the contrast agent echo and persistence. With the use of a video microscopy system coupled to either an ultrasound flow phantom or a chamber for insonifying stationary bubbles, we show that ultrasound has significant effects on encapsulated microbubbles. In vitro studies show that a train of ultrasound pulses can alter the structure of an albumin-shelled bubble, initiate various mechanisms of bubble destruction or produce aggregation that changes the echo spectrum.

Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles.

Rationale And Objectives: During echo examinations with microbubble contrast, individual "dots" of ultrasound reflection can be visualized. To address the question whether these signals represent individual microbubbles, very dilute suspensions of ultrasound contrast agents or individual microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging.

Methods: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system.

Targeted in vivo labeling of receptors for vascular endothelial growth factor: approach to identification of ischemic tissue.

Background: A method for identifying tissue experiencing hypoxic stress due to atherosclerotic vascular disease would be clinically useful. Vascular endothelial growth factor-121 (VEGF121) is an angiogenic protein secreted in response to hypoxia that binds to VEGF receptors overexpressed by ischemic microvasculature. We tested the hypothesis that VEGF receptors could serve as markers for ischemic tissue and hence provide a target for imaging such tissue with radiolabeled human VEGF121.

Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles.

On a time-domain representation of the Kramers-Kronig dispersion relations.

The development of Kramers-Kronig dispersion relations is typically carried out in the frequency domain. An alternative approach known as the time-causal theory develops dispersion relations for media with attenuation obeying a frequency power law through analysis in the time domain [T. L.

Kramers-Kronig relations applied to finite bandwidth data from suspensions of encapsulated microbubbles.

In this work, the Kramers-Kronig (K-K) relations are applied to experimental data of resonant nature by limiting the interval of integration to the measurement spectrum. The data are from suspensions of encapsulated microbubbles (Albunex) and have the characteristics of an ultrasonic notch filter. The goal is to test the consistency of this dispersion and attenuation data with the Kramers-Kronig relations in a strict manner, without any parameters from outside the experimental bandwidth entering in to the calculations.

Broadband time-domain reflectometry measurement of attenuation and phase velocity in highly attenuating suspensions with application to the ultrasound contrast medium Albunex.

We describe a technique for broadband measurements of the attenuation coefficient and phase velocity of highly attenuating liquid suspensions. To validate the technique we apply it to the ultrasound contrast agent Albunex at concentrations ranging from 0.69 x 10(6) particles/mL to 364 x 10(6) particles/mL.

On the applicability of Kramers-Kronig relations for ultrasonic attenuation obeying a frequency power law.

In the recent literature concern has been raised regarding the validity of Kramers-Kronig relations for media with ultrasonic attenuation obeying a frequency power law. It is demonstrated, however, that the Kramers-Kronig dispersion relations for application to these types of media are available. The developed dispersion relations are compared with measurements on several liquids, and agreement is found to better than 1 m/s over the experimentally available bandwidth.

Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes.

Background: Albumin microbubbles that are used for contrast echocardiography persist within the myocardial microcirculation after ischemia/reperfusion (I-R). The mechanism responsible for this phenomenon is unknown.

Methods And Results: Intravital microscopy of the microcirculation of exteriorized cremaster muscle was performed in 12 wild-type mice during intravenous injections of fluorescein-labeled microbubbles composed of albumin, anionic lipids, or cationic lipids.

Broadband measurement of the scattering-to-attenuation ratio for Albunex at 37 degrees C.

The attenuation coefficient and backscatter coefficient of Albunex were measured over a wide range of concentrations and frequencies (at a temperature of 37 degrees C), and were used to calculate the scattering-to-attenuation ratio (STAR) value. Each of these quantities exhibited concentration dependence in agreement with predictions from simple scattering theory: the backscatter coefficient grew linearly with concentration, the power of the transmitted signal decreased exponentially with concentration due to attenuation, and the STAR was independent of concentration scaling. Because of the markedly differing concentration dependence, it is necessary to consider all of these quantities (not just the STAR value alone) when evaluating and comparing the potential efficacy of ultrasonic contrast agents.

Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles.

The goal of targeted imaging is to produce an enhanced view of physiological processes or pathological tissue components. Contrast agents may improve the specificity of imaging modalities through selective targeting, and this may be particularly significant when using ultrasound (US) to image inflammatory processes or thrombi. One means of selective targeting involves the attachment of contrast agents to the desired site with the use of a specific binding mechanism.

Effects of transducer frequency and output power on the ultrasonographic contrast produced by Optison using fundamental and harmonic imaging techniques.

This in vivo study demonstrated the effects of transducer frequency and output power on the sonographic contrast produced by Optison during continuous ultrasonographic imaging in both fundamental and harmonic modes. During fundamental imaging, Optison produced greater contrast intensity while imaging at higher transducer frequencies. However, in the harmonic mode, lower imaging frequencies caused Optison to produce more intense myocardial enhancement.

Targeting and ultrasound imaging of microbubble-based contrast agents.

Preparation and characterization of targeted microbubbles (ultrasound contrast agents) is described. Specific ligands were attached to the microbubble shell, and ligand-coated microbubbles were selectively attached to various targets, using either an avidin biotin model system or an antigen-antibody system for targeting to live activated endothelial cells. Firm attachment of microbubbles to the target was achieved.

Effects of inhaled gases on the ultrasound contrast produced by microspheres containing air or perfluoropropane in anesthetized dogs.

Rationale And Objectives: Inhaled gas mixtures with increased amounts of oxygen cause air containing ultrasound contrast agents to lose efficacy faster than during the inhalation of air. The authors hypothesized that contrast materials containing relatively insoluble gases would decrease the effects of inhaled gases on the ultrasound contrast.

Methods: Anesthetized dogs were ventilated with compressed air and different oxygen/nitrogen gas mixtures.

Direct video-microscopic observation of the dynamic effects of medical ultrasound on ultrasound contrast microspheres.

Rationale And Objectives: Ultrasound can cause destruction of microbubble contrast agents used to enhance medical ultrasound imaging. This study sought to characterize the dynamics of this interaction by direct visual observation of microbubbles during insonification in vitro by a medical ultrasound imaging system.

Methods: Video microscopy was used to observe air-filled sonicated albumin microspheres adsorbed to a solid support during insonation.

Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells.

Background: Preclinical atherosclerosis is associated with increased endothelial cell (EC) expression of leukocyte adhesion molecules (LAMs), which mediate monocyte adhesion during atherogenesis. Identification of cell-surface LAMs may uniquely allow assessment of endothelial function, but there are no in vivo methods for detecting LAMs. We tested a new microbubble designed to bind to and allow specific ultrasound detection of intercellular adhesion molecule-1 (ICAM-1).

Broadband measurements of phase velocity in Albunex suspensions.

The phase velocities in suspensions of Albunex, an ultrasound contrast agent, are determined using the technique of broadband phase spectroscopy. In these suspensions, phase velocities were measured as a function of Albunex concentration in Isoton II (buffered saline). The dispersion over the measurement bandwidth (1-15 MHz) grew with increasing Albunex concentration, exhibiting a 221-m/s change (17% increase) in phase velocity between 1.

Targeting of ultrasound contrast material. An in vitro feasibility study.

Purpose: It would be beneficial to design a targetable microbubble ultrasound contrast agent that would selectively bind to the areas of interest in the body and enhance the target organ in the ultrasound examination.

Material And Methods: We have studied the feasibility of targeting in a model system. We used avidin and biotin as a model ligand-receptor pair.

Ultrasound velocity, through bone predicts incident vertebral deformity.

We followed 130 postmenopausal women without evidence of vertebral deformity by lateral spine radiographs on entry into study for 2 years, and repeat spine radiographs were taken at the end of that time. Incident deformities occurring within this 2 year period were detected by two methods, a level-specific radiogrammetric approach and visual inspection by skilled clinicians. Fourteen incident deformities were detected by the radiogrammetric method, and 19 by the clinicians.