Sonicated Albumin Microspheres Research Articles

Contrast echocardiography enhances tricuspid but not mitral reguargitation

Tricuspid regurgitation refers to a systolic leak of blood between the right ventricle and right atrium, across the tricuspid valve. Doppler echocardiographic examination of large numbers of normal individuals has shown that trivial tricuspid regurgitation is extremely common. Measurement of the peak velocity of the regurgitant frequency spectrum on Doppler echocardiography is of considerable clinical importance since it may be used to calculate peak right ventricular and, consequently, peak pulmonary systolic pressure. Doppler recording of the frequency spectrum of a tricuspid regurgitation jet optimally shows a smooth, parabolic, sharply demarcated envelope. In many individuals with trivial tricuspid regurgitation, however, this frequency spectrum is incomplete and its envelope is poorly demarcated. Such inadequate signals do not allow measurement of the spectrum's peak velocity. Like other contrast agents, air-filled microspheres composed of sonicated human serum albumin enhance reflection of Doppler ultrasound and thus have the potential to enhance incomplete tricuspid regurgitation spectra. Furthermore, since sonicated albumin microspheres can cross the pulmonary circulation intact, they have the potential to enhance mitral regurgitation spectra. The purpose of our study was to investigate whether injection of sonicated albumin microspheres enhances incomplete tricuspid and mitral regurgitation frequency spectra to a diagnostic quality. Sonicated albumin microsphere injection enhanced tricuspid regurgitation spectra to optimal quality in 11 of 15 patients (73%). Microsphere injection caused a minor degree of enhancement of the mitral regurgitant spectrum in 1 patient, but did not optimize the spectra in any of 10 patients tested. Saline contrast injection optimally enhanced tricuspid regurgitation spectra in all 8 patients in whom it was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of sonicated albumin microspheres in perfusion and vein graft patency assessments

This study was designed to identify a concentration of sonicated albumin microspheres that is safe, useful in determining graft patency, and provides an estimate of regional myocardial perfusion. The study included 8 patients between 50 and 72 years of age who were undergoing coronary artery bypass grafting. All patients were hemodynamically stable with left ventricular ejection fractions greater than or equal to 0.35. None had congestive heart failure or myocardial infarction within 4 months prior to the study. All had normal baseline neurologic and renal functions, and none had experienced allergic reactions to blood products or contrast dyes. A standard median sternotomy was performed for exposure of the heart at surgery, and saphenous veins were harvested and used for grafting. Intraoperative epicardial echocardiography (EE), always in the left ventricle short-axis at midpapillary level, was performed before and after grafting to determine regional myocardial wall motion. Sonicated albumin microspheres were prepared and injected into a single vein graft using an 18-gauge needle; 20 x 10(6), 100 x 10(6), and 200 x 10(6) microspheres were injected into the first graft sequentially. All other vein grafts were injected once with the dose that gave optimal contrast enhancement in the initial graft studied. In each patient, a minimum of 3 and maximum of 5 injections were performed, and graft perfusion was studied using EE. Graft flow, blood pressure, and electrocardiographic (ECG) measurements were continuously monitored, with a final EE performed after weaning the patient off cardiopulmonary bypass to assess wall motion. Preliminary results showed that no patient had adverse effects during or after the study and all remained hemodynamically stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of mean pixel intensity to concentration of sonicated albumin microspheres: Effects of ultrasound system settings

Myocardial contrast echocardiography (MCE) is a recently developed technique to assess myocardial perfusion. Previous studies have shown that MCE frequently underestimates coronary reserve as compared with other methods. Previous reports have suggested that some of the limitations of MCE are due to the nonlinear processing algorithms of the ultrasound systems. Therefore we designed an in vitro model to study the effects of various processing algorithms and levels of acoustic power (AP) on the relation between concentration of echocontrast and mean pixel intensities. A beaker containing a commercially produced, diluted solution of sonicated albumin microspheres was imaged with a commercial Hewlett Packard ultrasound system, and mean pixel intensities were determined with an off-line computer system. The solution was imaged at a wide range of APs (40-10 dB) and time gain compensation (40-60 dB). Concentration versus intensity curves were generated using all possible combinations of compression and processing algorithms available on the ultrasound system used. Contrast effect diminished rapidly when exposed to high AP. Lower powers had less effect on contrast intensity duration, with no effect seen below 20 dB. Changes in time gain compensation did not affect contrast intensities. Regardless of the processing algorithm examined, the relation between concentration of echocontrast and mean pixel intensities was near linear in the first two to three concentrations; thereafter, the curves flattened during increasing concentrations of contrast. At higher concentrations, acoustic shadowing produced a decrease in pixel intensities.(ABSTRACT TRUNCATED AT 250 WORDS)

Opacification and border delineation improvement in patients with suboptimal endocardial border definition on routine echocardiography: Results of a phase III trial of sonicated albumin microspheres

To determine whether contrast medium in the left ventricle improves endocardial border delineation, enabling better assessment of left ventricular (LV) wall motion, a 5% solution of sonicated albumin microspheres was administered in 30 adult patients who exhibited endocardial border drop-out of 20% or more on routine echocardiography. The investigator and two blinded reviewers evaluated efficacy using an opacification grading system of 0 to 3+, with 0 indicating no contrast effect and 3+ indicating full opacification of the left ventricle. A score of 2+ or greater indicated effective opacification. Border delineation improvement was defined as a change from grade A (not well delineated) to grade B, C, or D (well delineated) of at least 1 of 6 LV wall segments. All patients received an initial injection of 0.08 cc/kg. If this volume produced LV opacification of at least 2+, the patient received two additional injections of 0.14 cc/kg and 0.08 cc/kg, each given 5 minutes apart. Otherwise, the patient received a final injection of 0.22 cc/kg. In all cases, the patient's arm was raised after injection to enhance venous passage. The total number of patients exhibiting 2+ or greater opacification was 29 (97%) when graded by the investigator and 27 (90%) when graded by the blinded observers. The investigator noted improved border delineation in 90% of patients, and the blinded observers noted improvement in 97% (excluding 1 patient who would have received a higher dose of contrast agents if scored by a blinded observer). Investigator confidence in assessing LV wall motion improved in 24 (80%) of the 30 studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct video-microscopic observation of the dynamic effects of medical ultrasound on ultrasound contrast microspheres.

Ultrasound can cause destruction of microbubble contrast agents used to enhance medical ultrasound imaging. This study sought to characterize the dynamics of this interaction by direct visual observation of microbubbles during insonification in vitro by a medical ultrasound imaging system. Video microscopy was used to observe air-filled sonicated albumin microspheres adsorbed to a solid support during insonation. Deflation was not observed at lowest transmit power settings. At higher intensities, gas left the microparticle gradually, apparently dissolving into the surrounding medium. Deflation was slower for higher microsphere surface densities. Intermittent ultrasound imaging (0.5 Hz refresh rate) caused slower deflation than continuous imaging (33 Hz). Higher concentrations of microbubbles, lower ultrasound transmit power settings, and intermittent imaging each can reduce the rate of destruction of microspheres resulting from medical ultrasound insonation.

Sonography with sonicated albumin in the detection of vesicoureteral reflux

AbstractThe primary radiological procedures for diagnosing vesicoureteral reflux are fluoroscopic and radionuclide cystography. Ultrasonography, with no ionizing radiation, would be useful as a screening tool for the diagnosis of reflux due to its absence of radiation exposure. We evaluated the usefulness of ultrasonography with sonicated albumin in the diagnosis of vesicoureteral reflux. Sonicated albumin contains approximately 3 to 5 × 108 microspheres per ml., which are echogenic. Sonicated albumin was tested in vitro, alone, and in human and porcine urine to assess microsphere stability. Urine dilutions, specific gravity, temperature and pH were used as variables. The mode of delivery was also tested in vitro and in vivo. These studies showed that sonicated albumin microspheres were stable over a wide range of chemical variables and urine composition. Sonicated albumin produced an image of uniform echogenicity when it was pre-loaded into a Foley catheter and followed by saline infusion in vitro.Fluoro...

Sonography with Sonicated Albumin in the Detection of Vesicoureteral Reflux

The primary radiological procedures for diagnosing vesicoureteral reflux are fluoroscopic and radionuclide cystography. Ultrasonography, with no ionizing radiation, would be useful as a screening tool for the diagnosis of reflux due to its absence of radiation exposure. We evaluated the usefulness of ultrasonography with sonicated albumin in the diagnosis of vesicoureteral reflux. Sonicated albumin contains approximately 3 to 5 × 108 microspheres per ml., which are echogenic. Sonicated albumin was tested in vitro, alone, and in human and porcine urine to assess microsphere stability. Urine dilutions, specific gravity, temperature and pH were used as variables. The mode of delivery was also tested in vitro and in vivo. These studies showed that sonicated albumin microspheres were stable over a wide range of chemical variables and urine composition. Sonicated albumin produced an image of uniform echogenicity when it was pre-loaded into a Foley catheter and followed by saline infusion in vitro.Fluoroscopic cystograms, using standard radiopaque contrast media, in 5 Hanford mini-swine in which unilateral reflux had been created previously confirmed the presence of reflux unilaterally. Sonographic cystograms with various dilutions of sonicated albumin in 0.9% sodium chloride (1:100, 1:250, 1:500, 1:750 and 1:1,000) were performed. At a dilution of 1:100 sonicated albumin produced dramatic echogenicity in the bladder and refluxing ureters during sonographic imaging. The microspheres appeared to be stable for prolonged periods (more than 40 minutes), thus allowing for a careful sonographic assessment of the entire genitourinary tract. Sonicated albumin may be valuable for the sonographic detection of vesicoureteral reflux.

Assessment of renal blood flow with contrast ultrasonography.

Sonicated albumin microspheres, a digitalizing ultrasound system, and a mathematical model for flow were used to determine whether blood flow in the canine kidney could be assessed with contrast ultrasound. Albunex ultrasound contrast microspheres were injected into the aorta while ultrasound images of the kidney and aorta were recorded simultaneously. Ultrasound data were obtained during contrast injections at 93 different renal blood flow rates in nine dogs. Contrast dose was calibrated to ultrasound system response for both aortic and renal images. A linear relationship between microbubble concentration used and pixel intensity was established (r = 0.89 for aortic images and r = 0.91 for renal images). Renal blood flow was manipulated from baseline by means of a hydraulic renal artery occluder and by intravenous dopamine or fenoldopam infusion. Blood flow calculated with contrast ultrasonography was compared with direct measurement obtained with an electromagnetic flow probe at each flow rate. Direct measurement correlated with rates calculated with contrast ultrasonography (r = 0.84, 95% confidence limits from 0.75 to 0.90). Overall, calculations tended to overestimate absolute flow measurements, and overestimation of flow tended to be greater during pharmacologically manipulated flow rates. We conclude the changes and trends in renal blood flow can be serially assessed in vivo with contrast ultrasonography, but technical limitations of present commercial ultrasounds systems preclude absolute quantification at this time.

Contrast opacification of left ventricular myocardium following intravenous administration of sonicated albumin microspheres

Albunex is a new echocardiographic (2-D echo) contrast agent that traverses the pulmonary vasculature when injected intravenously in humans. We examined whether intravenous Albunex resulted in changes in myocardial intensity of sufficient magnitude to produce time intensity curves (TICs). Thirty mildly hypertensive patients were divided into three groups of 10. Each patient received three injections of intravenous Albunex (group I dosages: 0.01, 0.03, and 0.04 cm 3/kg; group II: 0.04, 0.06, and 0.08 cm 3/kg; group III: 0.08, 0.1, and 0.12 cm 3/kg) and two control injections of 5% human serum albumin while imaging with 2-D echo (phased-array; apical four-chamber). Fourty-three injections showed complete opacification of the left ventricle. Videointensity analysis of digitized end-diastolic frames produced myocardial TICs (total as well as background-substracted intensity curves) in 20 of 43 injections. By visual inspection, a myocardial contrast effect was seen in 10 of 43 injections. Detection of myocardial TICs was dose-related (0 of 7 in group I, 9 of 18 in group II, 11 of 18 in group III) and always paralleled the degree of left ventricular opacification. No myocardial contrast effect was observed in any patient during control injections of albumin or in any patient in whom the injection of Albunex did not result in left ventricular opacification. Thus myocardial opacification with intravenous Albunex can be detected simultaneously with good left ventricular opacification. The potential significance of the myocardial opacification observed is discussed.

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

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models.To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to + 3, with 0 indicating an absence of contrast effect and + 3 indicating full opacification of the cavities examined.All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opadfication ≥ + 2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related. In conclusion, this first multicenter clinical study of Albunex demonstrates that the contrast agent is safe when administered Intravenously and achieves significant transpulmonary passage in a majority of patients.

Sonicated Echocardiographic Contrast Agents: Reproducibility Studies

This article describes the production, analysis, and reproducibility of forming microbubbles for contrast ultrasound imaging. The sonication method used to generate microbubbles was tested by four independent observers, and a subsequent laser particle counter analysis of microbubble size and concentration determined the reproducibility of the method. The results indicated that the mean bubble size was 3.3 +/- 1.2 microns for the entire group, based on three trials of each of the four participants. The characteristics of the bubble size of the microbubbles between observers were assessed with a Poisson distribution with the reproducibility based on the sample mean for each observer's trials. Standardization and calibration of the laser particle counter was accomplished with commercially available latex spheres, sonicated albumin microspheres, and a Coulter counter analysis. Our results indicate that the sonication technique generates small microbubbles with a reproducible uniform size distribution. The method of microbubble production is reproducible and can be widely applied for use in contrast echocardiographic perfusion imaging of tissue in a variety of research and clinical studies.