Myocardial perfusion imaging with contrast ultrasound.

This report reviews the development and clinical application of myocardial perfusion imaging with myocardial contrast echocardiography (MCE). This includes the development of microbubble formulations that permit the detection of left ventricular contrast from venous injection and the imaging techniques that have been invented to detect the transit of these microbubbles through the microcirculation. The methods used to quantify myocardial perfusion during a continuous infusion of microbubbles are described.

Treatment of deeply located acute intravascular thrombi with therapeutic ultrasound guided by diagnostic ultrasound and intravenous microbubbles.

Objective: We sought to determine the added value of simultaneous imaging of intravenously infused microbubbles that are being used to dissolve an intravascular thrombus with therapeutic ultrasound (TUS).

Methods: In a chronic canine arteriovenous graft occluded by a thrombus, TUS (1 MHz) was applied through a 6-cm-thick tissue-mimicking phantom (measured mean +/- SD peak negative pressure through the phantom, 958 +/- 104 kPa) during an intravenous infusion of either saline (n = 6 occlusions) or lipid-encapsulated microbubbles (ImaRx Therapeutics, Inc, Tucson, AZ). Therapeutic ultrasound was intermittently applied during the microbubble infusion either at set time intervals (n = 6 occlusions) or when simultaneous diagnostic ultrasound (DUS) indicated a sustained presence of microbubbles (n = 12 occlusions).

Therapeutic ultrasound for gene delivery.

In vitro and in vivo studies using perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles to enhance gene delivery are reviewed. In vitro studies show PESDA binds to oligonucleotides and that ultrasound can be used to deposit these nucleotides. In addition, in vitro studies show that drug release from microspheres is dependent on ultrasound transmission frequency as well as pulsed or continuous application.

Inhibition of carotid artery neointimal formation with intravenous microbubbles.

Because therapeutic gene products such as synthetic antisense oligodeoxynucleotides (ODN) bind to albumin-coated microbubbles, we sought to determine whether IV perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles could target their delivery to the carotid artery following balloon injury. In 5 pigs, the concentration of ODN taken up within the carotid vascular wall was found to be significantly increased when the IV antisense (ODN) was administered bound to PESDA (ODN-PESDA), and while transcutaneous low-frequency (20 kHz) ultrasound was applied over the carotid artery. Based on these results, a chronic model was then developed, in which 21 pigs received either IV ODN-PESDA, ODN alone, or control, following carotid balloon injury.

Myocardial contrast echocardiography: a new gold standard for perfusion imaging?

Recent developments have permitted myocardial contrast echocardiography (MCE) to become a new method of noninvasively assessing myocardial perfusion in humans. Preliminary studies of myocardial perfusion imaging during adenosine, dipyridamole, and dobutamine stress echocardiography have shown excellent agreement with either radionuclide uptake or quantitative angiography. This article reviews the recent advances in microbubble technology, ultrasound imaging, and myocardial physiology that have made contrast echocardiography a potential new gold standard for perfusion imaging in the new millennium.

Effect of a Residual Stenosis by Quantitative Angiography on the Myocardial Contrast Defect Observed Following Coronary Reperfusion Using Intermittent Harmonic Ultrasound Imaging and Intravenous Perfluorocarbon Ultrasound Contrast.

Intermittent harmonic imaging following intravenously injected perfluorocarbon-containing microbubbles can detect myocardial perfusion abnormalities caused by ischemia. It is unknown whether this technique can differentiate viable, ischemic myocardium from infarcted myocardium immediately following coronary reperfusion. The objective of this paper was to determine whether intermittent harmonic imaging with intravenous microbubbles could define myocardial perfusion abnormalities following reperfusion.

Role of intravenous ultrasound contrast in stress echocardiography.

Intravenous newer generation perfluorocarbon containing microbubbles have been shown to enhance endocardial borders, especially during harmonic imaging. Although this significantly improves the detection of wall-motion abnormalities during stress echocardiography, intermittent imaging consistently results in myocardial contrast following intravenous infusions or injections of perfluorocarbon microbubbles. Detection of myocardial perfusion abnormalities during both exercise and pharmacologic stress echocardiography appears to be feasible clinically with either intravenous injections or continuous infusions of microbubbles using intermittent harmonic imaging.