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Dissolution of multicomponent microbubbles in the bloodstream: 1. Theory.

The problem of dissolution of a bubble in the bloodstream is examined. The bubble is assumed to be filled with a mixture of a sparingly water-soluble gas (osmotic agent) and air. The dissolution of the bubble has three definite stages. In Stage 1, the bubble quickly swells in air. The swelling ratio depends on the surface tension, blood pressure, level of oxygen metabolism and initial mole fraction of osmotic agent in the bubble. In Stage 2, the osmotic agent slowly diffuses out of the bubble. The squared radius decreases nearly linearly with time, at a rate proportional to the Ostwald coefficient and diffusivity of the osmotic agent. In Stage 3, the partial pressure of the osmotic agent becomes so high that it condenses into a liquid. In order to prolong the lifetime of 5-micron bubbles in the bloodstream from < 1 s (as found with pure air), the osmotic agent must have a low Ostwald coefficient (< or = 10(-4)) and a relatively high saturated vapor pressure at body temperature (> or = 0.3 atm = 3 x 10(4) Pa).

Air↗

Effect of high-intensity focused ultrasound on whole blood with and without microbubble contrast agent.

Using human whole blood samples with and without contrast agent (CA), we evaluated the effect of exposures to focused, continuous wave (CW) 1.1-MHz ultrasound for durations of 10 ms to 1 s at spatial average intensities of 560 to 2360 W/cm2. Cavitation was monitored with a passive cavitation detector and hemolysis was determined with spectroscopy. In whole blood alone, no significant cavitation, heating or hemolysis was detected at any exposure condition. Conversely, cavitation and hemolysis, but not heating, were detected in whole blood with CA. A CA concentration as low as 0.28 microL CA per mL whole blood at an intensity of 2360 W/cm2 for 1 s resulted in measurable cavitation and a 6-fold increase in hemolysis compared to shams. Cavitation and hemolysis increased proportional to the concentration of CA and duration of exposure. In samples containing 4.2 microL CA per mL whole blood exposed for 1 s, a threshold was seen at 1750 W/cm2 where cavitation and hemolysis increased 10-fold compared to exposures at lower intensities. HIFU exposure of whole blood containing CA leads to significant hemolysis in vitro and may lead to clinically significant hemolysis in vivo.

Albumins↗

Echocardiographic contrast agents: effect of microbubbles and carrier solutions on left ventricular contractility.

Recently, there has been a resurgence of interest in the use of contrast-enhanced echocardiography as a means of noninvasively assessing myocardial perfusion. However, if injections of echocardiographic contrast agents are to be used for this purpose it is essential that they are not intrinsically toxic to the heart. In this study, the left ventricular end-systolic wall stress-rate-corrected velocity of fiber shortening relation, a load independent index of contractility, was studied in nine dogs. Two-dimensional and targeted M-mode echocardiographic as well as central aortic pressure tracings were made during echocardiographically gated, pressure- and volume-controlled aortic root injections of nonsonicated and sonicated Renografin-76, saline and dextrose 70% (n = 6), and sonicated and hand-agitated Renografin-76/saline mixture (n = 5). Two of nine dogs received all agents. Off-line computer videodensitometric analysis documented myocardial perfusion. In all cases, data were obtained at control and 5 and 15 seconds after injection. Additional data were collected at 25 seconds after injection for the Renografin-76/saline mixture. Alterations in contractility were measured relative to control as changes in rate-corrected velocity of fiber shortening after afterload (measured as end-systolic wall stress) was eliminated as a confounding variable. Under no condition did saline or Renografin-76 cause alterations in left ventricular contractility. Nonsonicated and sonicated dextrose 70% increased left ventricular contractility at 15 seconds but not at 5 seconds after injection. Hand-agitated Renografin-76/saline mixture induced a negative inotropic effect at 5 and 15 seconds after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial contrast echocardiography in acute myocardial infarction using aortic root injections of microbubbles in conjunction with harmonic imaging: potential application in the cardiac catheterization laboratory.

OBJECTIVES: The aim of this study was to evaluate myocardial contrast echocardiography using aortic root injections with harmonic imaging in experimental acute myocardial infarction to determine the potential of this approach in the cardiac catheterization laboratory. BACKGROUND: It would be desirable to have an adjunctive procedure that could evaluate myocardial perfusion at the time of cardiac catheterization in patients with acute myocardial infarction. A single injection of contrast medium in the aortic root would provide complete information on myocardial perfusion in a cross section of the heart. High quality images would provide on-line assessment of myocardial perfusion without recourse to image processing. These data could be very valuable for determining patient management. METHODS: Perfusion defects on myocardial contrast echocardiography were measured during coronary occlusion and reflow, using fundamental and harmonic imaging in both continuous and intermittent modes in nine open chest dogs. These defects were compared with risk area on technetium-99m autoradiography and infarct size on tissue staining. RESULTS: Whereas harmonic imaging increased myocardial video intensity by more than twofold (p < 0.001) compared with fundamental imaging after aortic root injection of contrast medium, intermittent imaging was not superior to continuous imaging. The improved signal to noise ratio of harmonic imaging allowed on-line definition of risk area (r = 0.98) and infarct size (r = 0.93) without recourse to off-line processing. Similar results could be obtained with fundamental imaging only after off-line processing. CONCLUSIONS: Aortic root injection of contrast medium coupled with harmonic imaging can be used to provide accurate on-line assessment of risk area and infarct size during acute myocardial infarction. These results have important implications for the catheterization laboratory.

Adenosine↗

Reduction in left ventricular cavitary attenuation and improvement in posterior myocardial contrast with higher molecular weight intravenous perfluorocarbon-exposed sonicated dextrose albumin microbubbles.

Although intravenous perfluoropropane-exposed sonicated dextrose albumin (C3SDA) produces myocardial contrast, the posterior myocardium cannot be visualized with epicardial or transthoracic imaging because of excessive left ventricular cavitary contrast. We hypothesized that higher molecular weight, less diffusible gases such as perfluoropentane-exposed sonicated dextrose albumin (C5SDA) would produce equivalent anterior myocardial contrast at lower intravenous doses with less cavitary attenuation. To test this hypothesis, we compared the anterior and posterior peak myocardial videointensity after 0.06 ml/kg intravenous injections of C3SDA and 0.015 to 0.030 ml/kg intravenous injections of C5SDA in seven open-chest dogs. The ability of C5SDA to detect posterior myocardial perfusion abnormalities was also tested. Despite the lower dose, intravenous C5SDA produced equivalent anterior myocardial contrast but significantly higher posterior myocardial contrast (2.6 +/- 1.9 units peak myocardial videointensity C5SDA versus 0.6 +/- 0.9 units C3SDA; p < 0.0001) because of less acoustic shadowing. The visual detection of posterior ischemia with intravenous C5SDA was also significantly improved. We conclude that increasing the molecular weight of the perfluorocarbon gas in sonicated dextrose albumin will significantly improve the detection of posterior perfusion abnormalities.

Animals↗

Destruction of contrast microbubbles during ultrasound imaging at conventional power output.

Inhomogenous opacification of cardiac chambers has been frequently observed after intravenous administration of long-persisting echocardiographic contrast agents. We observed this phenomenon to be most pronounced at high acoustic powers with incomplete opacification of the left ventricular apex and left ventricular outflow tract. Reducing the acoustic energy to which the contrast was exposed by decreasing transmit power or intermittently suspending insonification resulted in homogenous opacification of the entire left ventricular cavity. We systematically examined the effect of varying insonification power on the persistence of three investigational ultrasound contrast agents in both in vitro and in vivo models. We found an inverse relationship between the insonifying power and the persistence of the contrast agents. Contrast intensity decay could be reduced either by decreasing exposure to ultrasound by minimizing the transmit power of the system or by intermittently suspending ultrasound generation (triggering). Minimization of ultrasound contrast exposure to ultrasound energy thus improves echocardiographic contrast duration and homogeneity.

Animals↗

B-mode enhancement of the liver with microbubble contrast agent: a blinded study in rabbits with VX2 tumors.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy of contrast material-enhanced sonography in the detection of liver lesions by using an animal model. MATERIALS AND METHODS: A total of 36 rabbits, 12 normal and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the study assignments. The sonographer assigned rabbits to four groups (no, one, two, more than two tumors) based on the number of lesions detected before and then after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments or pre- and postcontrast images were separated, randomized, and evaluated by a blinded reader. Necropsy served as the gold standard. RESULTS: Classification of rabbits as normal or tumor bearing on the precontrast images produced three false-positive results and three false-negative results for the blinded sonographer and six false-positive results and two false-negative results for the blinded reader. On postcontrast images, all rabbits were correctly classified by both observers. The correlation of the classification of whether rabbits had no, one, two, or more tumors relative to the pathologic classification on precontrast images was poor to fair (K = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111 for the reader), whereas the postcontrast correlation was good to excellent (K = 0.924 +/- 0.099 for the sonographer and 0.809 +/- 0.076 for the reader). CONCLUSION: AF0150 markedly increased the ability of the sonographer and the blinded reader to distinguish normal from tumor-bearing animals and improved the classification of rabbits with more than one liver tumor.

Animals↗