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Maturity of fetal lungs tested by production of stable microbubbles in amniotic fluid.

Lung surfactant in amniotic fluid, and hence the maturity of the fetal lungs, can be assessed by observation of stable microbubbles (less than 15 micron diameter). Bubbles are formed by agitation with a Pasteur pipette and examined in hanging drops under the 10 x power of a microscope. Either after a count of bubbles, or after a general survey of hanging drops, the fluid is given a stable microbubble rating. A 'strong' rating indicates that the idiopathic respiratory distress syndrome will not occur after delivery, and that the lecithin/sphingomyelin ratio will indicate maturity. Complete absence of stable microbubbles suggests a high risk of respiratory trouble for the newborn infant, as does a weak or lower rating in the 30 to 37 week gestational age group. The test takes 5 to 10 minutes to perform, is cheap and easy, is not affected by blood, but may be affected by meconium. If a 'strong' rating is found, measurement of the L/S ratio can safely be omitted.

Amniotic Fluid

The lung as a filter for microbubbles.

A new ultrasonic Doppler device has been used noninvasively over the femoral artery of anesthetized dogs to prove that it can detect carefully calibrated microbubbles of 14--189 micrometers diam when these are infused directly into the aorta. The same evaluated technique has then been employed to detect any bubbles escaping into the arterial system when gas was infused into the venous system either as microbubbles or as a bolus. Results from 18 dogs showed that, under normal conditions, the lungs are a superb filter for bubbles and that any cutoff diameter is less than 22 micrometers. However, bubbles escaped entrapment when the lungs were severely overloaded with gas (20 ml) or were pretreated with a pulmonary vasodilator (aminophylline). The dog preparation and arterial Doppler device appear to be ideal for future studies to determine what other factors might compromise the capability of the lungs to filter microbubbles. Physiological parameters showed dramatic changes when bubbles were detected as escaping into the arterial system by comparison with their effect when retained within the lungs. Changes in respiration profile indicated that they may offer a useful index of the degree of venous embolization and, hence, a warning of impending overload leading to arterial embolization.

Air

Microbubbles as a contrast agent for neurosonography and ultrasound-guided catheter manipulation: in vitro studies.

Tissue-equivalent ultrasound phantoms, including models of the ventricular system and cyst phantoms, may be useful for developing expertise in both biopsy procedures and shunt catheter placement that use ultrasound guidance. These phantoms have been constructed (1) to assess the ability to position biopsy needles and manipulate shunt catheters with conventional angiographic guidewires and (2) to evaluate the usefulness of microbubbles as an ultrasound contrast agent. Optimal catheter and needle position and catheter patency are demonstrated with microbubbles generated by hand injection of small volumes of saline, a safe ultrasound contrast agent that, to our knowledge, has not been previously exploited in neurosonography. Microbubbles can define biopsy needle location without direct imaging of the biopsy needle; they can also define the extent of communication or separation of fluid-filled or loculated spaces.

Air

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness.

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95% confidence interval [95% CI] = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (> 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95% CI = 0.89-0.95), compared to those with early onset (< or = 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Adult

M-mode ultrasonic detection of microbubbles following saturation diving: a case report and proposal for a new grading system.

An M-mode ultrasound system was used to obtain a reliable method for the evaluation of microbubbles caused by decompression. When the probe is focused in the outflow tract of the right ventricle it is easy to recognize a linear configuration of the echoes caused by the microbubbles. A quantitative study of microbubbles can be done by counting the number of linear echoes per second. Application of this method is reported following saturation diving decompression. We think the reported method is worthy of further use.

Decompression

A method for production of N2 microbubbles in platelet-rich plasma in an aggregometer-like apparatus, and effect on the platelet density in vitro.

The mechanisms involved in the interactions between microgasbubbles and platelets are not clear. The platelet aggregatory response to agonist-induced, receptor-mediated stimuli has been studied extensively. As a direct in vitro approach to elucidate the interaction between gas bubbles and platelets, N2 microbubbles were used as a platelet agonist in an experimental apparatus similar to an ordinary aggregometer. N2 microbubbles of varying number and size were produced in platelet-rich plasma (PRP) and incubated at 37 degrees C. The gas-liquid interface of the gas bubbles consists of plasma proteins and lipids. In stirred PRP a considerable decrease occurred in the platelet density, which could not be attributed to formation of citrate complexes with calcium and/or the corresponding reduction in the concentration of free calcium. Gas bubbles with a diameter in the range of 40-120 micron caused the greatest reduction in the platelet density. The platelet movements in PRP and the curvature of the N2 microbubble surface seemed more important for the interaction than the total gas bubble surface available for contact.

Analysis of Variance

Ultrasonic contrast study to indentify stomach tap water microbubbles.

In ultrasound scanning of the left upper quadrant of the abdomen, it is important to identify stomach contents which may appear as a cyst if the content is fluid or as a solid mass if the content is fluid with suspended food particles. By giving the patient a drink of two or three ounces of freshly drawn water, multiple strong echoes are produced from the fundus and the body of the stomach because of the microbubbles contained in recently agitated tap water and the microbubbles produced by the mixing effect of swallowing. These strong echoes will cause a "cystic" or "mass-like" appearance produced by the stomach contents to disappear. Thus, a false positive diagnosis is easily and rapidly avoided. The portion of the pancreas behind the stomach may also become more obvious. If the mass or cyst persists, the diagnosis of an abnormality is confirmed.

Diagnosis, Differential

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

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

Experimental frequency spectra of ultrasound transmission through two-dimensional ensembles of trapped microbubbles.

The frequency spectra of transmission coefficients for ultrasound passing through a sheet of gas-filled micropores have been measured using incident waves with amplitudes up to 2.4 x 10(4) Pa. It is found that as the amplitude of the incident wave is increased, the peak frequency of transmission loss through the two-dimensional trapped-bubble ensemble shifts to lower values by as much as 47%. The experiments indicate that the shifting is caused by the net displacements of air-water-membrane triple-phase lines and the air loss of the trapped bubble, which are due to the radiation force and microbubble production produced by the incident wave. Results of the experiments and possible theoretical explanations are discussed.

Ultrasonics

Hepatic tumors: US contrast enhancement with CO2 microbubbles.

Enhancement of hepatic tumors on sonograms by injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) was performed in 43 patients with various histologically confirmed hepatic tumors. Enhanced sonograms were classified into five patterns according to the relative changes of the echo levels between the tumor and the nontumorous parenchyma of the liver as a result of enhancement: hyperechoic change, isoechoic change, hypoechoic change with hyperechoic rim (rim sign), marginal spotty hyperechoic change, and internal spotty hyperechoic change. Eighty-eight percent of hepatocellular carcinomas showed hyperechoic change, 70% of metastatic tumors exhibited hypoechoic change with the rim sign. The marginal spotty hyperechoic change and the internal spotty hyperechoic change were specific for cavernous hemangioma and fibrous granuloma, respectively. This method of enhancement is useful in assessing the nature of liver tumors and in the detection of small nodules in the liver.

Carbon Dioxide

Hepatic focal nodular hyperplasia: specific findings at dynamic contrast-enhanced US with carbon dioxide microbubbles.

Dynamic contrast material-enhanced ultrasonography (US) with intraarterial infusion of carbon dioxide microbubbles was performed for four cases of histologically proved focal nodular hyperplasia (FNH) in four patients and for 167 cases of various hepatic nodules in 144 patients. No complications due to dynamic US were observed in any of the 148 patients. All FNH nodules were less than 3 cm in diameter. Consistent specific findings of FNH were not obtained with US, computed tomography, magnetic resonance imaging, radiocolloid scanning, or angiography in the four cases of FNH. In contrast, the characteristic vascular pattern (ie, early central hypervascular supply with centrifugal filling to the periphery at the arterial phase and a uniform or lobulated dense stain at the capillary phase) was observed in all four cases of FNH with dynamic US. This vascular pattern demonstrated in FNH with dynamic US was not seen in any of the 167 hepatic nodules, including 44 small hepatocellular carcinomas less than 3 cm in diameter. Therefore, the newly developed, dynamic contrast-enhanced US technique seems to be extremely sensitive and specific for diagnosing FNH and is useful in the differentiation of FNH from other hepatic tumors, especially hepatocellular carcinoma.

Adult

Small hepatocellular carcinoma: diagnosis with US angiography with intraarterial CO2 microbubbles.

Ultrasonographic (US) angiography enhanced with intraarterial CO2 microbubbles, a contrast material used in US imaging, was performed of 103 histologically proved hepatocellular carcinomas (HCCs) smaller than 3 cm in diameter in 95 patients. The detection rate for hypervascular HCC with US angiography was compared with the rate of detection with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil. Sensitivity in detection of hypervascular HCCs with US angiography was 86% (89 of 103 HCCs), compared with 63% (44 of 70 HCCs) detected with conventional angiography, 70% (23 of 33 HCCs) with DSA, and 82% (75 of 91 HCCs) with CT with iodized oil. US angiography depicted small hypervascular HCCs, especially those less than 1 cm in diameter, and helped clarify vascularity as isovascular or hypovascular in angiographically undetectable HCCs. Findings at US angiography assisted the choice of a therapeutic strategy for treatment of HCC, such as transarterial therapy, percutaneous ethanol injection therapy, or resection.

Angiography, Digital Subtraction

Microbubble elimination during priming improves biocompatibility of membrane oxygenators.

We tested the hypothesis that platelet loss following blood contact with foreign materials is partly related to the presence of microbubbles of gas (gas nuclei) trapped in surface defects on the membrane material. Extracorporeal membrane oxygenator perfusions were conducted in two groups of sheep, with use of standard priming techniques for the oxygenator in one group and a new vacuum priming technique in the other group. The vacuum priming technique was developed to eliminate gas nuclei from the oxygenator surface. With denucleation priming, platelet loss during perfusion was markedly reduced, as was thrombus formation on the membrane surface. The platelet particle-size distribution curve showed a shift consistent with platelet aggregation with the standard priming technique but not with the vacuum priming technique. We conclude that the elimination of trapped gas nuclei from the membrane surface during priming reduces the initial interaction between blood elements and the foreign surface.

Animals

Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors.

Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions.

Carbon Dioxide

[Prenatal assessment of fetal lung maturity by the stable microbubble method--fundamental and clinical study].

Diagnostic value of RDS was investigated by the Stable Microbubble Method. When this method was applied to the tracheal fluid of fetuses in rabbit (28 days of gestation), the PV curve and lung-thoracic compliance showed mature patterns in the test results for weak, medium, and strong as compared with those for zero and very weak in which they showed an immature pattern. Results by this method correlated with the DSPC level in human amniotic fluid, and were little affected by the contamination of meconium or fresh plasma. Amounts of DSPC were 0.69 +/- 0.05 (mg/dl, Mean +/- SE) in zero, 1.19 +/- 0.15 in very weak, 3.99 +/- 5.06 in weak, 6.58 +/- 2.01 in medium, and 7.70 +/- 1.15 in strong test results. The coefficient of correlation was 0.56 (p less than 0.01). In the clinical study, when the mature level was arbitrarily defined as weak, the diagnostic accuracy was 76.8%, false negative rate was 0%, and false positive rate was 27.5%. If the mature level was defined as very weak, the diagnostic accuracy was 94.2% and the false positive rate was 3.4%. But the false negative rate increased to 18.8%. The diagnostic accuracy of this method was higher than the double shake test (72.2%), and was as high as the measurement of the DSPC level (92.0%).

Amniotic Fluid