Blood-pool enhancement with SH U 508 A. Results of phase II clinical trials.
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Contrast Media↗
Biomedical subjects
R Schlief
Publications and source records attributed to R Schlief.
The effects of the microbubble suspension SH U 454 (Echovist) on ultrasound-induced cell lysis in a rotating tube exposure system.
Human erythrocytes resuspended at different hematocrits in autologous plasma at 37 degrees C were exposed to the therapeutic intensities of continuous-wave 0.75-MHz ultrasound in vitro in a rotating tube exposure apparatus designed to maximize the destructive effects of cavitational activity. Provided that large numbers of additional gas bubbles had not been introduced during the various preparative and manipulatory procedures, the addition of Echovist at final concentrations comparable with those currently being used for clinical investigations resulted in a statistically significant increase in the amount of cell lysis in vitro in those samples having hematocrits less than 2%. The amount of cell lysis produced at any given ultrasound intensity decreased with increasing hematocrit in both the controls and the cell suspensions containing Echovist until it was virtually zero in both cases at hematocrits of 5.5% or greater. The addition of Echovist to samples that already contained large numbers of stabilized gas bubbles and/or had hematocrits greater than 5.5% produced no detectable cell lysis even at ultrasonic intensities as high as 3 W/cm 2 spatial average, temporal average (SATA). It is therefore unlikely that Echovist would cause appreciable amounts of cell lysis when the gas bubbles were being exposed to ultrasound under the conditions used for clinical investigations in vivo.
Adult↗
Echo contrast agents improve flow display of color Doppler: in vitro studies.
Flow detection by color Doppler is impaired by low velocity of flow and increasing attenuation and depth of ultrasound penetration. The effects of increased echogenicity on flow detection (Toshiba SSH 65A) were thus studied in a flow model, which yielded similar strengths of Doppler signals as seen in the clinical routine, by adding microbubble solutions to the blood analog fluid (45% aqueous glycerin) and comparing signal strength (score 0-5) prior to and after contrast. The flow within the plexiglass tube with less than 3 degrees angle of coincidence for Doppler interrogation was laminar with a parabolic velocity profile at physiological velocities and pressures. In comparison with various contrast agents at a flow velocity of 18 cm/sec and 19 dB attenuation, flow was not detectable in control color Doppler, after 4 mL of the blood analog fluid, and after 4 mL of an agitated saline solution 9 mg/mL, but visible after 4 mL of Echovist, a polysaccharide solution with reproducible bubble size and concentration and after 4 mL of an agitated polygelatin solution. Increasing concentration of Echovist (50-400 mg/mL) improved flow detection. Echovist 200 mg/mL enhanced the score by 1.1 + -0.6 for velocities 5-20 cm/sec (P less than 0.01), by 1.6 + -0.8 for 40-100 cm/sec (P less than 0.001), and by 1.1 + -0.6 for velocities greater than 150 cm/sec (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Flow Velocity↗
Air microbubbles as a contrast medium in transcranial Doppler sonography. A pilot study.
An insufficient signal-to-noise ratio is a significant limiting factor in assessing intracranial hemodynamic parameters by transcranial Doppler sonography. To establish the feasibility and validity of signal enhancement in transcranial Doppler sonography, stabilized air microbubbles bound to galactose microparticles as a carrier (SHU 454) were used in an animal model. The disadvantage of a short-lasting effect is caused by instability of the contrast medium and a consequent reduced capacity to pass through the lung. Eight pigs received SHU 454 intraarterially in various concentrations and forms of application during transcranial monitoring of the middle cerebral artery with a 2 MHz pulsed ultrasound device. The effect was reproducible, dependent on the dose and application modalities. The best results were obtained with low concentrations (100 mg of microparticles/ml of suspension) and low injection speeds (0.5-1.0 ml/sec) into the common carotid artery by injection pump, reaching a homogeneous average enhancement of 6 to 12 dB over at least 5 minutes. Histological examination of the brain showed no evidence of air embolization. Further development requires a stable solution with similar properties and an ability to pass through the lung, therefore being suitable for intravenous application in humans.
Air↗
Hysterosalpingo-contrast sonography of the uterus and fallopian tubes: results of a clinical trial of a new contrast medium in 120 patients.
The feasibility, diagnostic efficacy, and patient tolerance of a new diagnostic modality, hysterosalpingo-contrast sonography (HyCoSy), were evaluated in a clinical study of 120 patients with suspected infertility. A new echogenic contrast medium for ultrasound was administered transcervically with conventional tools for hysterosalpingography or a balloon catheter. The flow of multiple fractions of the contrast medium through each fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe. All patent tubes were diagnosed correctly with HyCoSy, results comparing well with findings at hysterosalpingography or laparoscopy. With B-mode scanning only, sensitivity was 88% for the right tube and 90% for the left; specificity was 100% for each tube. The supplementary use of Doppler techniques (duplex, color Doppler) provided additional information in special cases of suspected tubal occlusion and led to an improvement in diagnostic accuracy. The contrast agent was well tolerated. HyCoSy demonstrates normal anatomy and tubal patency with high reliability and permits advance selection of patients in whom more invasive diagnostic procedures may be required.
Adult↗
Ultrasound contrast agents.
Two concepts of microbubble stabilization led to reproducible, industrially manufactured contrast agents, and to the transpulmonary stability of agents after intravenous injection. The albumin microencapsulation concept is represented by Albunex (Molecular Biosystems, San Diego, CA), the saccharide microparticle concept is represented by SH U 454 (Echovist and its transpulmonary derivative SH U 508 A, Schering AG, Berlin, FRG). In the past year, the first reported clinical studies of the transpulmonary agents have demonstrated their safety and efficacy. Further, the results of contrast-enhanced pulsed wave and color Doppler studies bring prospects of further improvements in vascular Doppler examinations. The patency of fallopian tubes was assessed with transvaginal scanning and transcervical injection of echogenic contrast agents. The feasibility of sonographic perfusion imaging of different organs (eg, myocardium, liver, tumors) was demonstrated using invasive injection techniques. Thus, ultrasound contrast agents are a new diagnostic tool in sonography and have a broad spectrum of potential indications.
Animals↗
Rat liver model for testing intraoperative echo contrast sonography.
The present animal experimental study showed that intraoperative hepatic ultrasonography using an echo contrast medium can visualize small hepatomas (with a diameter of between 3 and 15 mm) induced in the rat liver, although they were not recognizable with plain ultrasonography. A homogeneous increase in the echogenicity of the liver tissue was achieved by using an echo contrast medium (Echovist) based on galactose microparticles. Self-made bubble preparations such as those used in echocardiography were far less effective. When the dosage was optimal (0.01-0.003 ml/g liver weight with concentrations of 200 and 300 mg/ml Echovist), homogeneous contrast enhancement of the liver was achieved for at least 10 min after a single bolus injection via all routes of contrast administration (hepatic artery, portal vein, bile duct). As a result, hepatomas appeared as hypodense formations (portal vein and bile duct) or as hyperdense zones (hepatic artery).
Animals↗
[Dynamic contrast medium-aided ultrasound cavography in patients with a caval filter].
In 35 patients during 42 examinations, vena-caval blood flow was visualized by application of a new ultrasonic contrast medium (Echovist) via a dorsopedal vein. A caval filter had previously been implanted in 32 patients. In 94 out of 99 cases, application of the contrast medium allowed a diagnostically relevant enhancement of the echogenicity of the caval blood flow. In addition, the caval filters allowed altered flow geometry to be depicted in detail.
Adult↗
[Transvaginal contrast hysterosalpingo-sonography with the B-image procedure and color-coded duplex sonography for the assessment of fallopian tube patency].
Transvaginal hysterosalpingo-contrast-sonography (HYCOSY), a new method for the direct assessment of tubal patency by means of ultrasonography, was employed in 68 women with infertility problems. In 67 cases, the findings were compared with hysterosal-pinography or chromolaparoscopy, performed either subsequently while the patient was still under the anaesthetic or later. The contrast demonstration of the Fallopian tubes was performed with the B mode procedure in 54 cases (Group 1) and by means of colour-coded duplex sonography in 14 (Group 2). In Group 1, the findings agreed completely in 39 cases, partially in 14 and not at all in one. In Group 2, in which 13 of the 14 cases were compared, the findings were identical in 9 cases and partially in 4. From the point of view of image documentation, the more vivid demonstration of free tubal passage in colour Doppler sonography compared to the simple B mode appears to be an advantage. Further studies are needed to determine whether contrast-perfused but dislocated tubes can be detected more easily and quickly with colour Doppler than in B mode.
Adolescent↗
Successful opacification of the left heart chambers on echocardiographic examination after intravenous injection of a new saccharide based contrast agent.
A new monosaccharide microparticle based echocardiographic contrast agent (SH U 508) was injected intravenously into five healthy male volunteers following which the heart was imaged in an apical four-chamber view. Volumes of 2, 4, 8, and 16 mL of SH U 508 were incrementally injected into each volunteer. Concentrations of 50, 100, 200, 300, and 400 mg microparticles per mL of suspension were used in five successive examinations. Left heart opacification of diagnostic value was obtained during the whole cardiac cycle with concentrations of 300 and 400 mg/mL. There was no interference in imaging of the left ventricular walls due to increased attenuation. SH U 508 showed a good tolerance. No side effect was observed and no clinical relevant changes were observed in the heart rate, blood pressure, ECG, blood chemistry, hematology or urinalysis findings. This new agent may greatly extend the role of cardiac ultrasound and may also permit the examination of the arterial circulation in other organs.
Adult↗
Improved sensitivity of color Doppler by SH U 454.
SH U 454, a suspension of galactose microparticles, provides microbubbles (97% less than 7 microns) in variable, reproducible concentrations. Its influence on color Doppler imaging was evaluated in a flow model study and in a clinical study. In the flow model, increasing attenuation (up to 11.4 dB/MHz) impaired the signal to noise ratio and decreased the sensitivity for detecting flow velocities. Thus, flow signals were obtained with flow velocities greater than 3 cm/s (0.1 dB/MHz), greater than 9 cm/s (5.7 dB/MHz) and greater than 17 cm/s (11.4 dB/MHz). After injection of SH U 454 (200 mg/ml), velocities down to 3 cm/s were detected even with high attenuation (11.4 dB/MHz). Color Doppler imaging was performed before and after intravenous injection of 2 ml, 3 ml and 4 ml of SH U 454 (200 mg/ml) in 22 adult patients, and the maximal color-coded areas of diastolic blood flow were determined in the right atrium and ventricle. In 19 of 22 patients, the displayed color-coded areas increased after injection of SH U 454. The diastolic blood flow was imaged on 14 +/- 8% (mean +/- 1 standard deviation) of the cross-sectional area of the right ventricle (4-chamber view) without SH U 454, compared with 39 +/- 15% with 3 ml of SH U 454 (p less than 0.001). For the right atrium, the area displayed by color Doppler increased from 9 +/- 13 to 62 +/- 25% (p less than 0.001). The variability of the measurements from patient to patient after injection of SH U 454 was 5.9 +/- 4% as compared with 10.7 +/- 6.9% without SH U 454 (p less than 0.05). These findings indicate that the intravenous injection of SH U 454 increases the sensitivity of color Doppler imaging for detection of blood flow by improving the signal to noise ratio.
Adult↗
[Contrast-color Doppler echocardiography. Improved right heart diagnosis following intravenous injection of Echovist].
Flow patterns in the right heart are often difficult to visualize by color-coded Doppler flow imaging. The echogenicity of blood was increased in 48 patients by intravenous injection of 10 ml echovist (200 mg/ml), a saccharide solution with defined size and concentration of microbubbles. Its effect on improving color-coding was compared with the effect of agitated gelifundol (10 ml) in 21 patients with tricuspid valve regurgitation. The non-controlled size and concentration of microbubbles resulted in weaker or uncontrollably exaggerated color-coding in half of the patients. In eight normals biphasic atrial flow was visible only after injection of echovist. In 25 patients with tricuspid regurgitation the blue coded area of reflux was 25 +/- 21% of the atrial area from the parasternal approach and 10 +/- 9% from the apical approach without correlation of these results. After echovist the area of reflux was 57 +/- 31% (p less than 0.001) in the parasternal and 53 +/- 26% (p less than 0.001) in the apical approach (r = 0.83). This was paralleled by an increase of the severity of tricuspid regurgitation as defined by the length or area of reflux (p less than 0.01-0.001). The qualitative diagnosis was safely established in the five patients with VSD in the control color Doppler flow imaging, but only in three out of 10 patients with ASD, and in nine of 10 after injection of echovist. The intravenous injection of echovist, when using color-coded Doppler flow imaging for evaluation of right heart disease, facilitates the qualitative diagnosis of ASD and also of tricuspid regurgitation, particularly in the apical approach.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Improving color Doppler echocardiography of the right heart chambers following intravenous injection of SHU 454].
The echocardiographic contrast agent SHU 454 provides microbubbles of defined size (median 3 micron) in a solution of galactose and is available in different reproducible concentrations. In 22 patients with suspected tricuspid regurgitation, color flow mapping (CFM) Doppler echocardiography was performed before and after intravenous injection of 2-4 ml SHU 454. Without SHU 454 the diastolic blood flow was imaged on 13.6 +/- 7.5% (mean value + standard deviation) of the cross sectional area of the right ventricle (four-chamber view) in comparison to 39.0 +/- 15.0% with SHU 454 (p less than 0.001). For the right atrium, the area analyzed by CFM increased from 9.4 +/- 12.9% to 62.4 +/- 25.3% (p less than 0.001). The interindividual variability of measurements after injection of SHU 454 was 5.9 +/- 4.0% as compared to 10.7 +/- 6.9% without SHU 454 (p less than 0.05). These findings demonstrate that intravenous SHU 454 administration increases the detection of blood flow by CFM within the right heart.
Adult↗
Hemodynamic effects of microbubble echo contrast.
The dose-related hemodynamic effects of an active (bubble-rich) echo contrast agent were compared with those of a bubble-free contrast agent and saline solution to determine whether the microbubbles contained in the echo contrast agent are truly passive indicators in the circulation or whether they actively alter the hemodynamic state independent of the volume and osmotic loading associated with such injections. The study population consisted of 13 fully instrumented open-chest mongrel dogs. Four hundred ninety-two bolus injections were made of three different types: active contrast agent (Levovist, Schering AG, Berlin) (n = 333), saline solution (n = 112), and bubble-free contrast agent (n = 47). Levovist was administered in five dose ranges spanning 0.013 to 0.341 gm/kg and, like the saline solution, was administered in bolus volumes of 0.053 to 1.136 ml/kg. For each injection type, the percent change in hemodynamic parameters after administration of the bolus were calculated on the basis of the dose or volume of the injectate. Audio Doppler signal intensity was used to document the presence of bubbles in the injectate. Statistical significance was defined at the p = 0.05 level; clinical significance was defined as a greater than 15% change in a hemodynamic parameter. Statistically, but not clinically, significant changes were noted in almost all hemodynamic parameters regardless of injection type, and at all dose and volume ranges. Although statistically significant, injection of an active contrast agent in the human dose range resulted in a < 5% change in hemodynamic parameters. High doses of a contrast agent (active or bubble-free) increased the left atrial pressure and had associated changes in peripheral vascular hemodynamics because of the osmotic load. Clinically significant increases (> 15%) in pulmonary artery pressure and pulmonary vascular resistance were unique to the active contrast agent at high dose ranges. Standard doses of the active contrast agent changed the hemodynamics by less than 5% in healthy dogs. Transient clinically significant increases in pulmonary artery pressure and pulmonary vascular resistance are a unique side effect to high dose bolus injections of microbubble echo contrast agent.
Animals↗
Molecular recognition. Feeling for the bumps.
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Amino Acids↗