We review the field of contrast agents in diagnostic ultrasound. The progress in the development of various classes of contrast agents such as free and encapsulated gas bubbles, colloidal suspensions, emulsions, and aqueous solutions is described. The mechanisms for production of backscatter contrast, as well as attenuation contrast and speed of sound contrast are explained. Finally, the potential advantages and disadvantages of various classes of contrast agents are compared.

Contrast agents in diagnostic ultrasound.

Two-dimensional contrast echocardiography. I. In vitro development and quantitative analysis of echo contrast agents

Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results.

Myocardial contrast echocardiography (MCE) is a new technique for assessing myocardial perfusion that uses intracoronary injections of microbubbles of air. Because these microbubbles have a mean diameter of 4.3 +/- 0.3 microns and an intravascular rheology similar to that of red blood cells (RBCs), we hypothesized that their mean myocardial transit rates recorded on echocardiography would provide an estimation of regional myocardial blood flow in the in vivo beating heart. Accordingly, blood flow to the left anterior descending coronary artery (LAD) of 12 open-chest anesthetized dogs (group I) was adjusted to 4 to 6 flows (total of 60 flows), and microbubbles and radiolabeled RBCs were injected into the LAD in a random order at each stage. The mean myocardial RBC transit rates were measured by fitting a gamma-variate function to time-activity plots generated by placing a miniature CsI2 probe over the anterior surface of the heart, and the mean myocardial microbubble transit rates were measured from time-intensity plots derived from off-line analysis of MCE images obtained during the injection of microbubbles. An excellent correlation was noted between flow (measured with an extracorporeal electromagnetic flow probe) and mean myocardial RBC transit rate (y = 2.83 x 10(-3)x + 0.01, r = .96, SEE = 0.02, P < .001). A close correlation was also noted between mean RBC and microbubble myocardial transit rates (y = 1.01x + 0.01, r = .89, SEE = 0.02, P < .001). Despite its theoretical advantages, a lagged normal density function did not provide a better fit to the MCE data than the gamma-variate function.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography. Comparison with radiolabeled red blood cells.

This review discusses the development, current applications, and therapeutic potential of ultrasound contrast agents. Microbubbles containing gases act as true, intravascular indicators, permitting a noninvasive, quantitative analysis of the spatial and temporal heterogeneity of blood flow and volumes within the microvasculature. These shelled microbubbles are near-perfect reflectors of acoustic ultrasound energy and, when injected intravenously into the bloodstream, reflect ultrasound waves within the capillaries without disrupting the local environment. Accordingly, microbubble ultrasound contrast agents are clinically useful in enhancing ultrasound images and improving the accuracy of diagnoses. More recently, ultrasound contrast agents have been used to directly visualize the vasa vasorum and neovascularization of atherosclerotic carotid artery plaques, thus suggesting a new paradigm for diagnosis and treatment of atherosclerosis. Future applications of these microscopic agents include the deliver of site-specific therapy to targeted organs in the body. Medical therapies may use these microbubbles as carriers for newer therapeutic options.

https://www.physiology.org/doi/pdf/10.1152/ajpheart.00134.2004

The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond

A new echocardiographic contrast agent, gelatin-encapsulated microbubbles, that an intramyocardial contrast effect, was evaluated as a marker for the detection of regions of abnormal myocardial perfusion in nine open-chest dogs. The gelatin-encapsulated microbubbles were injected into the aortic root under control conditions and during circumflex coronary artery occlusion. Myocardial perfusion was simultaneously assessed with radioactive microspheres. Echocardiographic contrast enhancement (ECE) was measured in footlamberts (Ft-L) from the videoscreen of an off-line playback system, using a commercially available light meter. A single short-axis section of the left ventricle was divided into octants to analyze myocardial perfusion. The equivalent regions of the echocardiographic image were analyzed for contrast enhancement and wall motion. An ECE > 0.3 Ft-L was seen in all 120 octants analyzed before circumflex coronary artery occlusion and in 48 of 51 (94%) octants with > 50% of normal zone flow during circumflex artery occlusion. An ECE ≤ 0.3 Ft-L identified 19 of 21 octants (with ≤ 50% normal zone flow and all 13 octants with ≤ 25% normal zone flow during coronary artery occlusion. In contrast, wall motion abnormalities (akinesis or dyskinesis) were seen in 13 of 51 octants (25%) with > 50% normal zone flow, and normal wall motion was seen in two of 21 octants (10%) with blood flow ≤ 50% of normal zone flow during circumflex coronary artery occlusion. We could not demonstrate a linear correlation between ECE and the absolute level of myocardial blood flow. We feel this was due to the limitations imposed by imaging an open-chest animal preparation, variation in the number of gelatin-encapsulated microbubbles used for each injection and variations in the echocardiographic gain settings among experiments. We conclude that contrast-enhanced two-dimensional echocardiography with gelatin-encapsulated microbubbles can accurately identify ischemic regions of the left ventricular myocardium. This technique is more accurate than wall motion analysis for detecting myocardial ischemia.

T M Mueller

Papers

Assessment of myocardial perfusion abnormalities with contrast-enhanced two-dimensional echocardiography.