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Contrast echocardiography: effects of microbubbles on coronary blood flow and left ventricular hemodynamics.

Contrast echocardiography is currently being used to define and quantitate myocardial perfusion at the time of cardiac catheterization. Limited and conflicting data exist regarding the physiologic effects of microbubble-containing contrast agents. In the present study, coronary blood flow measured using an electromagnetic flow meter, blood pressure, and heart rate responses were studied in six dogs. An ECG-gated power injector was used to deliver 7 to 9 ml of sonicated and nonsonicated solutions (saline, Renografin-76, dextrose 50% and 70%, and sorbitol 70%) through an intra-aortic catheter placed above the aortic cusps. Paired injections of sonicated and nonsonicated agents were compared to determine whether the presence of microbubbles affected the physiologic response to these agents. Simultaneous recordings of two-dimensional cross-sectional images of the left ventricle were obtained. Data are expressed as percentage of change from preinjection control values. Within 10 seconds of an injection, decreases in coronary blood flow occurred in a range from -1 to -10% compared with preinjection control values. Coronary blood flow increased between 10 and 25 seconds postinjection within a range from +11 to +29%. Systemic blood pressures rose during injections and then declined below control values within 10 seconds. The magnitude of the decline in systolic blood pressure ranged from -5. to -18%. Diastolic blood pressure declined in a range from -13 to -33%. Within 20-30 seconds postinjection, systemic blood pressure rose above control values. The magnitude of the systolic and diastolic blood pressure rise ranged from +4 to +11%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial contrast echocardiography: examination of intracoronary injections, microbubble diameters, and video-intensity decay.

Contrast echocardiographic assessment of blood flow within the myocardium requires standardization of contrast agents and echo image analysis. Sonicated contrast solutions containing small and relatively stable microbubble ultrasound reflectors were injected into coronary arteries of five dogs, and a newly developed computer assisted densitometric analysis of myocardial echo intensity decay was examined. The sonicated solutions included sorbitol 70%, dextrose 70%, and dextrose 50%, and myocardial contrast echo data were analyzed by applying an exponential decay index (T-1/2) to the digitized time intensity curves obtained with videodensitometric techniques. In 30 intracoronary injections selected for further analysis, sonicated sorbitol 70% demonstrated the most physiologic myocardial transit time with the smallest variability (6.0 +/- 2.0 seconds). Sonicated dextrose 70% and dextrose 50% solutions exhibited significantly prolonged and more variable transit times (11.4 +/- 4.0 seconds and 13.9 +/- 5.0 seconds). The results of this study suggest that appropriate echo contrast solutions with small microbubble diameters are critical to satisfactory echocardiographic assessment of myocardial blood flow, and that objective analysis of contrast two-dimensional echocardiographic images can be achieved with computer-assisted videodensity algorithms featuring standardized echo analysis of the time intensity data.

Animals↗

Stable microbubble test for predicting the occurrence of respiratory distress syndrome.

To predict the development of respiratory distress syndrome (RDS) in premature neonates who might benefit from early administration of surfactant, the clinical applicability of stable microbubble (SM) test was prospectively evaluated. Fifty-nine preterm neonates with the gestational ages of less than 37 weeks were studied. SM test was performed on gastric aspirates obtained within 30 minutes after birth. The number of microbubbles was correlated with later development of RDS. With a cut-off value of less than 10 microbubbles/mm2, the SM test showed a positive predictive value of 76.0% (19/25) and a negative predictive value of 97.1% (33/34), while sensitivity and specificity were 95.0% (19/20) and 84.6% (33/39), respectively. The overall accuracy was 88.1% (52/59). It was concluded that use of the SM test on gastric aspirates immediately after birth is a rapid, simple and reliable procedure for identifying those neonates with surfactant deficiency who may benefit from prophylactic surfactant therapy.

Gastric Juice↗

Utility of Doppler-detectable microbubbles in the diagnosis and treatment of decompression sickness.

BACKGROUND: Doppler-detectable microbubbles (DMB) are frequently used to evaluate altitude decompression stress. However, the role of DMB in the therapy of decompression sickness (DCS) has not been examined. HYPOTHESIS: The ability of Doppler to detect microbubbles during decompression (Doppler test) may be used in the diagnosis of DCS, and to aid clinical decisions about treatment options for DCS. METHODS: We examined the data on DMB and symptoms from NASA Database on DCS (n = 516). The accuracy of Doppler test was obtained from the Receiver Operating Characteristic (ROC) for DMB (grades I through IV), and efficacy was obtained by calculating predictive or post-test probabilities. Threshold analysis was used to obtain the probabilities for testing and/or treatment decisions. RESULTS: The Doppler test was useful for both screening and confirming DCS, when different criteria (grade I for screening; grade IV for confirming) were used for a positive test. Calculation of predictive values and threshold analysis showed that: 1) early recompression was the therapy of choice when post-test probability of disease was > 0.25 in individuals with non-specific pain at altitude, and early recompression with 100% oxygen for 2 h at site level was optimal therapy when this probability was > 0.33; 2) hyperbaric therapy was optimal when post-test probability was > 0.04 in individuals with uncertain symptoms post-flight. CONCLUSIONS: The Doppler test was of greater utility in excluding DCS than confirming its presence, and was useful in making therapeutic decisions on DCS when confronted with non-specific symptoms at altitude.

Aerospace Medicine↗

Prediction of idiopathic respiratory distress syndrome by the stable microbubble test on gastric aspirate.

We evaluated the usefulness and accuracy of the stable microbubble test (SMT) performed on gastric aspirates of neonates to predict idiopathic respiratory distress syndrome (IRDS) and compared the results with those of the shake test, using the clinical characteristics of IRDS as the gold standard for the diagnosis of IRDS. One hundred forty paired samples of gastric aspirates, obtained within 1 hour of delivery from neonates with gestational ages between 27 and 42 weeks (mean, 36.6+/-3.5 weeks) and birth weights between 800 and 4,090 grams (mean 2,571+/-826 grams ) were evaluated. The sensitivity and specificity of the SMT with a predefined cut-off value of less than 20 bubbles/mm2 were 94.7% and 95%, respectively, with a positive and negative predictive value of 75% and 99.1%, respectively. The positive predictive value and specificity were increased to 100% in premature neonates. These values, especially the positive predictive value and specificity, were much higher than those obtained with the shake test. We conclude that the SMT on gastric aspirates obtained within 1 hour of delivery is a rapid and simple procedure to identify those neonates who will develop IRDS and who may benefit from prophylactic exogenous surfactant replacement.

Chi-Square Distribution↗

Dynamic contrast-enhanced ultrasound with carbon dioxide microbubbles as adjunct to arteriography of liver tumors.

PURPOSE: The goal of the study is to evaluate utility of contrast-enhanced ultrasound (US) with carbon dioxide microbubbles in evaluation of hepatic lesions. METHODS: Twenty-eight patients with single or multiple hepatic lesions (11 hepatocellular carcinoma, 8 hemangiomas, 5 metastases, 1 adenoma, 1 focal nodular hyperplasia, 2 regenerative nodules) were examined. US exam was performed during intraarterial injection of 10 ml of CO2 through the same catheter employed for liver arteriography. The US exam was videotaped in its salient phases. Characteristics of enhancement were evaluated and correlated with histological findings or patient follow-up. RESULTS: Sonographic angiography clearly demonstrated vascularization of the lesions. Hepatocellular carcinoma, hemangioma, metastases, focal nodular hyperplasia, and regenerative nodules had very characteristic patterns. The injection of CO2 allowed detection of small additional nodules. CONCLUSION: Sonographic angiography can improve characterization and staging of hepatic tumors. Low cost and the simplicity of the technique should encourage further experimentation.

Angiography, Digital Subtraction↗

Internalization of microbubbles by tumor cells in vivo and in vitro.

Lipid-coated microbubbles (LCM) administered intravenously (i.v.) to rats bearing brain tumor, specifically enhance tumor visualization by ultrasound [1]. In order to understand the basis for this observation, we have examined the interactions of LCM with glioblastoma (C6) and gliosarcoma (9L) tumor cells in vivo and in vitro. LCM and LCM labeled with the fluorescent lipophilic dye 3,3'-dioctadecyloxacarbocyanine perchlorate (diO) were administered to rats bearing brain tumor. LCM and diO-labeled LCM were found principally at the tumor site with no evidence of label in the surrounding normal brain tissue. Analysis of the tumor by confocal laser scanning microscopy revealed that labeled LCM were inside the tumor cells. Similar analysis of LCM interactions with C6 and 9L cells in culture showed that LCM first adsorb at the surface of the cells, and with time became localized inside the cells. Binding and internalization proceeded faster at 37 degrees C than at room temperature (RT). Staining of live cells with N-(3-((2,4-dinitrophenyl)amino)propyl)-N-(3-aminopropyl) methylamine dihydrochloride (DAMP), a dye that recognizes acidic compartments, showed that the majority of internalized LCM was associated with compartments containing DAMP. If the same uptake mechanism were operative in vivo, it would indicate that a portion of LCM bypasses the reticuloendothelial system and become endocytosed directly by tumor cells.

Animals↗

Stable microbubble test for predicting the risk of respiratory distress syndrome: I. Comparisons with other predictors of fetal lung maturity in amniotic fluid.

With the advent of surfactant replacement therapy, there is an increasing need for a rapid test of predicting the development of respiratory distress syndrome (RDS). We evaluated the clinical usefulness of the stable microbubble (SM) test in predicting the development of RDS by comparison with other tests in amniotic fluid samples obtained within 12 h before delivery from 40 pregnancies between 23-35 weeks of gestation. These tests included the lecithin/sphingomyelin (L/S) ratio, disaturated phosphatidylcholine/sphingomyelin (DSPC/S) ratio, concentrations of lecithin, DSPC, and surfactant-associated proteins A and B, C (SP-A, SP-B,C). The cut-off value of each test for predicting RDS was determined at a point of maximum diagnostic accuracy. The overall diagnostic accuracy of the SM test was similar to that of other tests. However, both the SM test and the SP-B,C concentration had positive predictive values of 100%. We conclude that the rapid (< 10 min) and reliable information obtained by this test should encourage its use in defining a population of neonates with surfactant deficiency in a multicentre trial of prophylactic surfactant therapy.

Amniotic Fluid↗

Stable microbubble test for predicting the risk of respiratory distress syndrome: II. Prospective evaluation of the test on amniotic fluid and gastric aspirate.

We determined prospectively if the stable microbubble (SM) test on gastric aspirate obtained at birth was as useful as that on amniotic fluid in predicting respiratory distress syndrome (RDS). One hundred and five paired samples of amniotic fluid obtained at delivery from 105 consecutive women with gestation of 35 weeks or less and gastric aspirates from their neonates obtained within 30 min of birth were studied. The SM test with the predefined cut-off value of less than 5 bubbles/mm2 for amniotic fluid and less than 10 bubbles/mm2 for gastric aspirate signified the risk of RDS with the positive predictive value of 100% and 96% and with the negative predictive value of 91% and 84%, respectively. We conclude that the SM test on both amniotic fluid and gastric aspirate obtained at birth is a rapid (< 10 min), simple and reliable procedure for predicting neonates who will develop RDS. It may be used as a bedside test to define a population of neonates with surfactant deficiency in clinical trials of prophylactic surfactant therapy.

Amniotic Fluid↗

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant.

UNLABELLED: Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. CONCLUSION: Surfactant therapy normalizes the surfactant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients.

Albumins↗

Myocardial risk area and peak gray level measurement by contrast echocardiography: effect of microbubble size and concentration, injection rate, and coronary vasodilation.

Contrast agents were injected via the intracoronary route in eight dogs during two-dimensional echocardiographic imaging to determine the influence of microbubble size and concentration, injection rate, and coronary vasodilation on risk area and peak gray level measurement. At an injection rate at 13 cc/sec, the average background-subtracted peak gray level intensity of hand-agitated diatrizoate meglumine/diatrizoate sodium was significantly (p less than 0.01) higher than that of hand-agitated diatrizoate meglumine/diatrizoate sodium + 0.9% saline, sonicated diatrizoate meglumine/diatrizoate sodium, and sonicated 70% sorbitol. These differences were abolished by the use of 38 cc/sec injection rates and intracoronary injection of adenosine. Perfusion area determinations as assessed by planimetry were unaffected by the contrast agent used, the injection rate, or by intracoronary administration of adenosine. We conclude that risk area measurement by the ultrasound contrast technique is not affected by varying contrast agents, injection rates, or vasodilation. However, peak gray level intensity is variable among contrast agents and may result in variability of time-activity curve analysis.

Animals↗

Microbubble image enhancement and pericardiocentesis.

When performing pericardiocentesis, if blood-stained fluid is aspirated, one must ensure that the aspirating needle is not within one of the cardiac chambers. To clarify the position of the needle some contrast material may be injected using X-ray screening and for this reason pericardiocentesis is often performed in the catheter laboratory, particularly if the effusion is small, loculated or the heart is in an unusual position. Ultrasound immaging is now commonly used to guide the aspirating needle and if blood-stained fluid is withdrawn we reinject a few millilitres and this outlines the space from which the fluid is withdrawn with microbubbles. This modification of ultrasound immaging adds to the safety of the procedure and allows difficult procedures to be carried out in the ward or intensive care unit, where X-rays screening is not easily available.

Adolescent↗

Applications of lipid-coated microbubble ultrasonic contrast to tumor therapy.

Lipid-coated microbubbles (LCM) make an excellent diagnostic ultrasonic contrast agent in experimental tumor systems. LCM have been shown to aggregate in brain tumors and subcutaneous tumors after intravenous administration, and to provide persistent image enhancement for many minutes. In this work, experimental subcutaneous Walker Carcinosarcoma is insonated after the bubbles are given intravenously. Selective necrosis, lymphocyte proliferation and hemorrhage within the tumor can be demonstrated. Preliminary data are given to demonstrate this phenomenon. The mechanism of the effect is discussed in the context of both heating and cavitation.

Animals↗

The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction.

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function.

Aged↗

Use of microbubble ultrasound contrast agent to demonstrate the iris valve effect in human eye bank eyes.

PURPOSE: To demonstrate that the interface between the normal iris and the lens surface functions as a flap valve. METHOD: Microbubble ultrasound contrast agent was injected into the anterior and posterior chambers of human eye bank eyes and the distribution of contrast imaged with high-frequency ultrasound. RESULTS: Contrast agent did not enter the posterior chamber when injected into the anterior chamber, but contrast agent injected into the posterior chamber easily flowed into the anterior chamber. CONCLUSIONS: The iris-lens interface normally functions as a flap valve, preventing retrograde flow from the anterior to the posterior chamber. A temporary increase in anterior chamber pressure thus results in iris concavity in pigmentary dispersion syndrome.

Adult↗

The acoustics of diagnostic microbubbles: dissipative effects and heat deposition.

We discuss the effectively detectable scattered intensity of ultrasound from diagnostic microbubble suspensions, taking dissipative mechanisms in the liquid medium into account. In particular, we conclude that neither non-linear wave steepening of the incident (driving) wave nor of the outgoing (scattered) wave has a large effect on the scattered signal from typical bubbles. It is shown that, paradoxically, the far-field solution of the wave field is sufficient to compute the magnitude of expected temperature rises in the medium due to acoustic heat deposition, although appreciable heating is limited to intermediate-field distances from the bubble surface.

Acoustics↗