shu-508 and perflutren

The development of new contrast agents and new imaging methods has lead to an emerging field of applications for myocardial contrast echocardiography (MCE) in patients suffering from chronic ischemic heart disease. Echo contrast allows the assessment of myocardial perfusion (MP) by imaging the coronary microcirculation. Several echocardiographic modalities are available, the main difference between them being the acoustic power needed to perform the study. MP is evaluated by assessing the changes in myocardial videointensity that occur after intravenous contrast injection. Evaluation of these patients is performed by using different techniques. Evaluation of coronary stenosis may be performed by using stress tests or without its use. Coronary artery stenosis > 50% of the coronary luminal diameter reveals a decreased hyperemic response when myocardial oxygen demand is increased. Different methods to evaluate the presence of relevant coronary stenosis have been developed: evaluation of myocardial blood flow reserve, evaluation of myocardial blood volume, and evaluation of the transmural distribution of myocardial blood flow. The combination of wall motion analysis with MCE assessment has been demonstrated to achieve the best balance between sensitivity (86%) and specificity (88%), with the highest accuracy (86%). Without the need of any stress, the ratio systolic/diastolic myocardial blood volume has been described to increase with the presence of a epicardial coronary stenosis and it may be measured by MCE. Myocardial viability is also one of the potentials of MCE. Microvascular integrity, demonstrated by MCE, is an indicator of preserved viability and predicts functional recovery that has been validated in the setting of chronic left ventricular dysfunction secondary to chronic coronary artery disease and in the setting of post acute myocardial infarction left ventricular dysfunction.. contrast echocardiography provides an interesting tool that offers the potential of a complete evaluation of patients with chronic coronary artery disease. This includes both diagnostic and prognostic evaluation.

Topics: Albumins; Blood Volume; Chronic Disease; Contrast Media; Coronary Circulation; Coronary Disease; Echocardiography; Fluorocarbons; Humans; Microcirculation; Phospholipids; Polysaccharides; Prognosis; Sulfur Hexafluoride

Topics: Adult; Albumins; Child; Contrast Media; Endosonography; Female; Fluorocarbons; Humans; Image Enhancement; Liver; Male; Phospholipids; Polysaccharides; Sensitivity and Specificity; Sulfur Hexafluoride; Ultrasonography; Ultrasonography, Doppler

Topics: Albumins; Carcinoma, Hepatocellular; Cholangiocarcinoma; Contrast Media; Diagnosis, Differential; Fluorocarbons; Humans; Image Enhancement; Liver Neoplasms; Microbubbles; Phospholipids; Polysaccharides; Sulfur Hexafluoride; Ultrasonography, Interventional; Vesico-Ureteral Reflux

Liver metastases lead to a shortening of the HTT of an echo enhancer. Studies using SonoVue™ also showed a shortening of the HTT in healthy controls. Hence the HTT depends on the applied contrast agent. We examined whether the HTT of SonoVue™, Luminity™ und Levovist™ is useful to discriminate between patients with and without liver metastases.. We compared the arteriovenous HTT of Levovist™, Sonovue™ und Luminity™ in 20 patients with liver metastases and in 15 controls. An Acuson Sequoia™ ultrasound system was used. The HTT results from the difference of the arrival time of the microbubbles in the hepatic artery and a hepatic vein.. Using Levovist™ six patients and three controls had to be excluded from further analysis. The arrival time was undetectable. The mean HTT values in healthy controls were: Levovsit™ 14.75 sec (SD ± 2.53 sec), SonoVue™ 9.27 sec (SD ± 2.41 sec) and Luminity™ 9.2 sec (SD ± 2.34 sec). In patients the mean HTT values were: Levovist™ 9.89 sec (SD ± 1.04 sec), SonoVue™ 6.28 sec (SD ± 2.41 sec) and Luminity™ 6.33 sec (SD ± 1.37 sec). Using a cut off of 8 sec for SonoVue™ and Luminity™, the sensitivity to exclude liver metastases was 75% and 80%.. The mean HTT values of all contrast agents were shorter in patients. Levovist™ showed a longer HTT in patients and controls than Luminity™ and SonoVue™. Levovist™ showed the best separation between patients and controls but some patients and controls had to be excluded. The HTT could still be a useful tool to exclude liver metastases but the HTT depends on the contrast agent and the applied contrast technique.

Topics: Adult; Aged; Contrast Media; Female; Fluorocarbons; Humans; Image Enhancement; Liver Neoplasms; Male; Metabolic Clearance Rate; Middle Aged; Phospholipids; Polysaccharides; Reference Values; Sulfur Hexafluoride; Ultrasonography

The differences in time-related changes of liver images were compared quantitatively between Levovist and Definity. A total of 40 rabbits were assigned to eight groups according to the timing of taking enhanced liver images at 1, 3, 5, 7, 9, 11, 13 and 15 min by intermittent harmonic imaging using Levovist or Definity (30 microL/kg) and another 40 rabbits for Definity (50 microL/kg). Intensity changes between before and after enhancement in the portal vein (I-PV) and liver parenchyma (I-LP) were analyzed. I-PV was greater than I-LP at the 1- and 3-min phases of enhancement and I-LP became greater than I-PV with Levovist after 5 min. However, I-PV was higher than I-LP in all phases with Definity. Different time-intensity curves of these two agents will indicate discrete behaviors of microbubble hemodynamics in the liver; Levovist becomes accumulated in the liver, whereas Definity acts as a blood pool contrast agent, without accumulation.

Topics: Animals; Contrast Media; Fluorocarbons; Image Processing, Computer-Assisted; Liver; Male; Microbubbles; Polysaccharides; Rabbits; Ultrasonography

Single intravenous administration of three different gas-carrier contrast agents used in ultrasound imaging to mice caused inflammation, necrosis, and ulceration of cecum and proximal colon (cecocolonic area) and focal necrosis in the liver. Similar intestinal lesions were also found in rats after treatment with a single iv administration of a gas-carrier contrast agent. Strain differences in the incidences of these lesions were found in both rats and mice. HsdHan:NMRI mice were among the most sensitive of the strains of mice studied. Even at the lowest dose of Sonazoid technically possible to inject in HsdHan:NMRI mice, lesions were found and a no-effect dose could not be determined. In a time-course experiment in HsdHan:NMRI mice, it was found that the lesions began to develop in the cecum and colon within 15 to 30 min after dosing. Lesions in the liver were first observed 120-240 min after dosing. Diet played a role in the etiology of the lesions, as HsdHan:NMRI mice given a diet with reduced amounts of cellulose and starch had reduced incidences of lesions, and when glucose was the only carbohydrate source, no lesions were observed. No intestinal or hepatic lesions were found in guinea pigs or rabbits after repeated intravenous administrations of Sonazoid. In dogs, minimal to mild granulocytic inflammation of the cecum and/or colon was found after daily repeated intravenous injections for 28 days, but not after daily repeated administration for 14 days nor after a single administration. It is proposed that the intestinal and hepatic lesions in rats and mice after a single intravenous injection of gas-carrier contrast agents are caused by a common mechanism: intravascular growth of gas-carrier agents in tissues with gas supersaturation, as occurs in the cecal wall of rats and mice. In this particular environment the growing gas bubbles cause ischemia and necrosis in the cecal and colonic wall and liver. This proposed mechanism of action is consistent with the absence of clinical reports indicative of intestinal and/or hepatic lesions in humans after administration of gas-carrier contrast agents.

Topics: Administration, Oral; Albumins; Animal Feed; Animals; Contrast Media; Dogs; Dose-Response Relationship, Drug; Female; Ferric Compounds; Fluorocarbons; Gases; Guinea Pigs; Injections, Intravenous; Intestinal Mucosa; Intestine, Large; Iron; Liver; Male; Mice; Mice, Inbred Strains; Necrosis; Oxides; Polysaccharides; Rabbits; Rats; Rats, Inbred Strains; Species Specificity; Ultrasonography

Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0 ml/kg) or Levovist (300 mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0 ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting.

Topics: Animals; Blood Vessels; Contrast Media; Dose-Response Relationship, Drug; Endothelium, Vascular; Fluorocarbons; Hemorrhage; Injections, Intravenous; Male; Microcirculation; Microspheres; Polysaccharides; Rats; Rats, Wistar; Splanchnic Circulation; Ultrasonography

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.

Topics: Animals; Chemical Phenomena; Chemistry, Physical; Contrast Media; Dogs; Echocardiography; Fluorocarbons; Image Enhancement; Microspheres; Polysaccharides; Pressure; Time Factors

Although ultrasound contrast microbubbles theoretically could serve as tracers for the noninvasive quantification of blood flow, results have been inconsistent. Accurate quantification may be limited by ultrasound energy-mediated microbubble destruction. This study examined the effect of different ultrasound delivery parameters on microbubble destruction.. Experiments were performed in an in vitro hydraulic perfusion model consisting of a thin-walled rubber tube encased in agar. Ultrasonic parameters tested during different parts of the experiment were (1) intensity, (2) duration, and (3) frequency. Four ultrasound contrast agents: Aerosomes MRX115 (ImaRx Pharmaceuticals Corp., Tucson, AZ), Imagent AF0150 US (Alliance Pharmaceutical Corp., San Diego, CA), Levovist (Berlex Laboratories, Wayne, NJ), and Echogen (Sonus Pharmaceuticals, Bothel, WA) were imaged with three different ultrasound systems: ATL Ultramark AM-9 HDI, Vingmed 800 and Hewlett-Packard 2500.. Microbubble destruction and reductions in reflectivity were noted in all agents tested. Although no significant reductions in counts or reflectivity occurred at 0.3 W/cm2 with any agent, exposure to 25 W/cm2 produced more than 80% reductions in both microbubble counts (P < 0.0001) and reflectivity (P < 0.0001). Declines in reflectivity were increased by longer exposure to ultrasound (P < 0.0001); slower flow through an ultrasound beam (P < 0.0001); continuous, rather than intermittent, imaging (P = 0.0002); use of a higher pulse repetition rate (P < 0.0001); and exposure to 2.5 MHz, rather than 7.5 MHz, ultrasound (P < 0.0001).. Ultrasound energy-mediated destruction of contrast microbubbles is a function of many factors, including ultrasound intensity, duration, and frequency. Optimization of ultrasound delivery parameters may be used to maximize or minimize the destruction of ultrasound contrast agents.

Topics: Contrast Media; Echocardiography; Fluorocarbons; Models, Theoretical; Polysaccharides