Stimulated acoustic emission imaging ("sono-scintigraphy") with the ultrasound contrast agent Levovist: a reproducible Doppler ultrasound effect with potential clinical utility.
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Adult↗
Biomedical subjects
R Schlief
Publications and source records attributed to R Schlief.
A mathematical model for the assessment of hemodynamic parameters using quantitative contrast echocardiography.
A mathematical model for the assessment of hemodynamic parameters using quantitative echocardiography is presented. The method involves the intravenous injection of an ultrasonic echo contrast agent. The relative enhancement of the backscattered ultrasound intensity is measured as a function of time (the time-intensity curve). From this measurement, the volume flow rate (cardiac output) and the mixing volume are calculated. Relevant acoustic properties of the ultrasound contrast agent are discussed. An in vitro experiment is performed to corroborate the theory presented.
Calibration↗
Prolongation and optimization of Doppler enhancement with a microbubble US contrast agent by using continuous infusion: preliminary experience.
PURPOSE: To investigate whether continuous infusion of an echo-enhancing contrast agent for up to 15 minutes can provide uniform and prolonged enhancement. MATERIALS AND METHODS: Six volunteers each received one bolus and three infusions of a microbubble contrast agent over 6-15 minutes at (a) a standard rate (mean, 2.08 mL/min), (b) a fast rate at twice the standard rate, and (c) a slow rate at half the standard rate. Spectral Doppler intensitometry of the femoral artery was performed for all infusions. Spectral Doppler ultrasound (US) scans of the femoral artery and color Doppler US scans of the carotid artery were subjectively assessed. RESULTS: All infusions provided an equilibrium plateau of constant prolonged enhancement starting after 1-2 minutes and lasting until the end of the infusion. Enhancement at the plateau was +13 dB (slow rate), +17.1 dB (standard rate), and +18.3 dB (fast rate) compared with baseline. Saturation artifacts with infusions were markedly fewer than those with bolus injections. Dose effectiveness (duration of enhancement that measured at least 7.5 dB per gram of contrast agent) was markedly improved with the infusions, from 0.8 min/g for the bolus to 2.6 min/g for the slow infusion. CONCLUSION: Continuous infusion of the microbubble contrast agent provided prolonged and uniform enhancement of Doppler signals and improved image quality by minimizing saturation artifacts.
Adult↗
Assessment of fetal and placental blood flow in primates using contrast enhanced ultrasonography.
Ultrasonographic contrast agents that stay within the vascular space and do not cross the placenta may permit differentiation between the maternal and fetal portions of the placenta and may be clinically useful for diagnosis of placental abnormalities. This study was performed to assess the effects of Levovist (Schering AG, Berlin) on the placental circulation and to determine whether hemodynamic effects on the fetus occur. Ten studies were performed in five pregnant macaques (median weight, 9.15 kg; range, 6.15 to 11 kg; median gestational age, 121 days; range, 34 days to term) under anesthesia. Gray scale, color, and duplex Doppler sonographic scans of the fetus and placenta were acquired using a 5 MHz curved array transducer. Fetal heart rate, resistive index, and systolic-diastolic ratios were measured in the fetal middle cerebral artery, aorta, umbilical artery, and uterine artery before and after administration of contrast agent. The following dose regimen was tested: 5 ml of physiologic saline solution followed by 0.1 ml/kg of 300 mg/ml Levovist (diagnostic dose), 0.5 ml/kg of 400 mg/ml Levovist (maximum dose), and 5 ml physiologic saline solution. The order of diagnostic dose and maximal dose was randomized among animals. Color enhancement of the basal portions of the placenta was documented after administration of contrast agent. Heart rate and middle cerebral artery systolic-diastolic ratio did not change between baseline and injections. A 7% decrease of the resistive index from baseline to maximum dose was measured in the uterine artery (not significant). A 7.7% decrease in the systolic-diastolic ratio from baseline to maximum dose was recorded in the umbilical artery. However, an identical change was measured after saline solution was injected. The resistive index in the aorta increased by 2.6% from baseline to maximum dose, a change that was not significant (P > 0.5). Ultrasonographic contrast enhancement of the maternal circulation in placenta is demonstrated to be without significant effects on the fetal circulation as measured in this limited population.
Analysis of Variance↗
An investigation of the relationship between ultrasound echo enhancement and Doppler frequency shift using a pulsatile arterial flow phantom.
RATIONALE AND OBJECTIVES: Based on the echo-enhancing effect of microbubbles, various agents have been developed to improve the diagnostic confidence in patients with inadequate Doppler signals. In the clinical trials of the echo enhancer Levovist, there were a few isolated cases in which the maximum flow velocities of the enhanced Doppler spectra appeared to higher than the velocities in the nonenhanced baseline spectra. This raised the concern that echo enhancement could give a false indication of maximum flow velocity. This study investigated whether a systematic association between echo enhancement and velocity shift exists. METHODS: A pulsatile flow phantom that simulated the elasticity of blood vessels and the acoustic attenuation of extravascular tissue was used to compare enhanced with unenhanced Doppler spectra under accurately reproducible flow conditions. The experiments were carried out with varied sound attenuation and evaluated with dedicated spectral analysis software that included a special averaging tool. RESULTS: Levovist enhanced the Doppler signal by 16 to 31 dB, and the enhanced and unenhanced power spectra presented identical distribution of spectral power density under all flow conditions. CONCLUSIONS: The measurements gave no evidence that echo enhancement with Levovist falsifies the Doppler measurement of flow velocity.
Blood Flow Velocity↗
Color doppler ultrasound of liver lesions: signal enhancement after intravenous injection of the ultrasound contrast agent Levovist.
Patients with focal liver lesions (hemangioma, focal nodular hyperplasia, adenoma, hepatocellular carcinoma, metastatic lesions, focal fatty lesion) received the ultrasound contrast agent Levovist (300 mg/mL and 400 mg/mL) intravenously. This ultrasound contrast agent (a suspension of micrometer-sized microparticles of galactose and microscopic gaseous bubbles) can pass through the lungs without impairment. After the administration of Levovist, increased color flow signals were detected in the liver. Five of 6 patients with metastatic liver lesions showed previously undetected blood flow in the rim of the tumor. In 4 patients with hepatocellular carcinoma, enhanced signal intensity was observed in the vessels of the rim and in 3 of those patients in the center of the tumor. One patient with adenoma and one patient with focal nodular hyperplasia showed signal enhancement in the central area of the tumor. No signal enhancement was observed in hemangiomas, a focal fatty lesion, or in a carcinoid metastatic lesion. Levovist increased the echointensity of normal and tumor vessels in liver lesions. This new ultrasound contrast agent led to the detection of tumor vessels previously not detectable by conventional color flow imaging.
Adenoma↗
[Ultrasound contrast media. New perspectives in ultrasound diagnosis].
Ultrasound contrast agents have recently proven to be clinically useful in many different areas and with many different ultrasound modalities. B-mode contrast echocardiography and delineation of cavities with ultrasound contrast agents are already accepted. Based on the contrast agent Echovist, assessment of tubal patency is possible with hysterosalpingo contrast sonography (HyCoSy). A new generation of transpulmonary, stable ultrasound contrast agents such as Levovist offer potential for various Doppler applications. Ultrasound contrast agents act as signal enhancers in Doppler examinations and therefore help to overcome the limitations of insufficient Doppler signal intensity. Recently, clinical studies have shown [correction of shown.] Doppler examinations to have many clinical benefits. Contrast agents are useful in the assessment of high-grade stenosis or the delineation of small vessels and under difficult conditions. Ultrasound contrast agents also create new applications: analysis of tumor vascularization and delineation of the transcranial venous system are possible with contrast enhancement. Future developments in contrast-specific scanning ("harmonic imaging") and new contrast agents, including organ-specific contrast agents, are expected to make a significant impact in the years to come.
Contrast Media↗
The Doppler kinetics of microbubble echo contrast.
The right and left heart kinetics of a saccharide-based microbubble echo contrast agent were measured in 11 anesthetized dogs using Doppler intensity as a measure of microbubble concentration while controlling for the dose administered, weight of the subject and cardiac output. A two-phase Doppler time-intensity curve was noted in all vascular regions. A brief first pass effect (phase 1) was found to depend on the contrast dose, cardiac output and subject size. This was followed by a much longer nearly steady-state elevation in the Doppler intensity compared with baseline (phase 2). The kinetics of phase 2 were found to be the same in all vascular distributions and independent of cardiac output. The phase 2 kinetics depend on the contrast dose, subject size and elimination characteristics of the contrast agent. The clinically important conclusions are: (1) the magnitude of Doppler enhancement and duration of the contrast effect can be predicted using the simple formulas presented; (2) the flow-dependent portion of the arterial contrast effect is effectively over only a few seconds after intravenous injection; and (3) the kinetics of phase 2 are the same throughout the body.
Animals↗
Blood-pool echo enhancement after intravenous injection of galactose-based microbubbles: results from European phase III clinical trials in Doppler sonography.
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Contrast Media↗
Contrast enhancement in leg vessels.
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Animals↗
Developments in echo-enhancing agents.
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Albumins↗
Future prospects for echo-enhancing agents.
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Acoustics↗
Improvement of endocardial border delineation in suboptimal stress-echocardiograms using the new left heart contrast agent SH U 508 A.
Recent studies have shown that the saccharide based echocardiographic contrast agent SH U 508 A opacifies the left ventricle after i.v. injection, thus possibly improving endocardial border definition. This study was performed to determine whether SH U 508 A can enhance the wall motion analysis in suboptimal echocardiographic images at rest and following pharmacological stress. Ten male patients (mean 58 years) exhibiting > or = 30% endocardial border dropout were examined prior to a diagnostic left heart catheterization. Five patients were stressed with Dobutamine, 5 with Dipyridamole. The wall motion was assessed visually (qualitatively) as well as computer-aided (quantitatively). The concordance between left ventricular angiography as 'gold standard' and resting echocardiography regarding the wall motion analysis was significantly improved from 64.5% to 90.3% following the injection of SH U 508 A (p < 0.05). A delineation score (0 = not delineated, 1 = delineated) of 12 individual wall segments was used. The mean delineation score at baseline was 6.1 +/- 1.4 at rest and 6.6 +/- 1.9 during stress. SH U 508 A significantly (p < 0.01) increased the score to 9.6 +/- 1.9 and 10.3 +/- 1.7, respectively. The intraobserver variability for assessing the delineation score was significantly (p < 0.04) improved by SH U 508 A. SH U 508 A, however, did not improve the quantitative assessment of the left ventricular function. Only 40% of the patients could be analyzed following SH U 508 A injection. No severe adverse reactions were seen. SH U 508 A led to a significant, clinically important, improvement in the interpretation of stress echocardiograms in patients with inconclusive routine echocardiograms.
Adult↗
Improved Doppler signal intensity in coronary arteries after intravenous peripheral injection of a lung-crossing contrast agent (SHU 508A)
OBJECTIVES: We tested the hypothesis that SHU 508A, a new lung-crossing contrast agent capable of increasing the Doppler signal to noise ratio in the right heart as well as left heart cavities after intravenous injection, could increase Doppler signal intensity in coronary arteries, thus improving the feasibility and quality of transesophageal Doppler echocardiographic evaluation of coronary blood flow velocity. BACKGROUND: Coronary blood flow velocity can be evaluated by transesophageal Doppler echocardiography. However, an adequate Doppler tracing is obtainable in a relatively low percent of patients. METHODS: Transesophageal Doppler echocardiography of coronary arteries was performed in 35 patients before and after SHU 508A injection at four different dosages (200 mg/ml in 5 ml, 200 mg/ml in 10 ml, 300 mg/ml in 5 ml and 300 mg/ml in 10 ml). Color Doppler mapping of coronary flow and pulsed wave Doppler measurement of coronary blood flow velocity were attempted in all patients. RESULTS: Color Doppler flow mapping of 105 evaluated coronary segments (left main, left anterior descending and circumflex in 35 patients) was not detectable or was weak in 88% of patients before and 33% of patients after echo contrast injection (p < 0.0001); it was optimal (that is, well delineated with complete flow mapping of the explored vessel) in only 11% of patients before and 67% after echo contrast injection (p < 0.0001). In addition, pulsed wave Doppler signal quality improved after echo contrast injection: Pulsed wave Doppler recording of coronary blood flow velocity was not obtainable or was weak in 78% of cases before and 34% after echo contrast injection (p < 0.0001); pulsed wave Doppler recording of coronary blood flow velocity was optimal (that is, there was a complete and well defined outline of diastolic coronary blood flow velocity in 23% of cases before and 66% after echo contrast injection [p < 0.0001]. Both length and width of color Doppler mapping in the left anterior descending coronary artery increased after SHU 508A injection (from 5.75 +/- 5.32 and 1.51 +/- 1.17 to 17.04 +/- 8.76 and 4.21 +/- 1.78 mm, respectively, mean +/- SD, p < 0.0001). CONCLUSIONS: The feasibility and quality of recording coronary blood flow velocity by transesophageal Doppler echocardiography are considerably improved by intravenous injection of SHU 508A. The improved feasibility of this new semi-invasive method for evaluating coronary blood flow velocity and flow reserve can considerably increase its research and clinical utilization.
Aged↗
Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography.
PURPOSE: To study the potential of contrast material-enhanced transcranial color-coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization. MATERIALS AND METHODS: Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography. RESULTS: All lesions were hyperechoic on B-mode US scans except one grade 2 astrocytoma. The location and extent of hyperechoic lesions correlated well with findings on CT scans and MR images. After injection of contrast material, color Doppler flow signals were seen in nine of 14 low-grade lesions and 14 of 14 high-grade lesions. High-grade malignant tumors always had atypical arterial and venous Doppler spectra with irregular distribution of Doppler shift and signal intensities; these atypical flow patterns were also detected in some low-grade tumors. CONCLUSION: In addition to depiction of primary CNS tumors in B-mode, contrast-enhanced TCCS enables evaluation of vascularization associated with tumor parenchyma.
Adult↗
Doppler enhancement with SH U 508A in multiple vascular regions.
PURPOSE: To determine the magnitude and duration of peripheral vascular and cardiac Doppler signal enhancement after intravenous administration of contrast agent SH U 508A. MATERIALS AND METHODS: Suboptimal cardiac or peripheral vascular Doppler examinations were evaluated. A total of 75 intravenous bolus injections were made in 30 patients. Spectral audio Doppler intensity was measured throughout the duration of contrast effect. RESULTS: No clinically relevant adverse effects were noted, and Doppler enhancement was apparent in all cases. The diagnostic confidence of the investigators when scored before and after Doppler enhancement improved from 35% to 91% (P < .05). Doppler intensity increased more than 16 dB in all vascular regions investigated (P < .05). The contrast effect lasted for more than 120 seconds in the peripheral vascular and cardiac groups at equivalent doses. CONCLUSION: Intravenously administered SH U 508A is effective in markedly increasing cardiac, femoral arterial, and transcranial (cerebral arterial) Doppler signal intensity. The effect improves the clinical diagnostic confidence in cases of suboptimal unenhanced Doppler examinations.
Cerebral Arterial Diseases↗
Saccharide-based contrast agents. Characteristics and diagnostic potential.
Since about 1980 tiny bubbles of gas ("microbubbles") have been known to be highly effective in ultrasonography because of enhancing backscatter ultrasound. After about 25 years of experimental work, the first industrial US contrast agent was approved by health authorities, the galactose microparticle SH U 454-Echovist, Schering AG, launched on the German market in 1991. Its major limitation is represented by the fact that it does not pass the pulmonary barrier and is confined to right heart abnormalities. Therefore another agent has been developed, the transpulmonary derivative of Echovist the galactose-based agent with the code number SH U 508 A (Levovist) which is in the late phase of clinical development for cardiac B-mode and Doppler blood pool US enhancement. A wide number of application areas can be foreseen for this contrast agent, which has been used for a multicenter trial. More than 1,200 patients were included in a European phase-III multicenter trial aimed at assessing the diagnostic efficacy and safety of SH U 508 A (Levovist). The patients included in the study had diagnostically insufficient Doppler signal intensity at routine Doppler or color Doppler vascular imaging. In more than 95% of the patients Doppler signal enhancement was achieved with at least one dose at the scheduled regimen, even in peripheral vessels. Enhanced Doppler US allowed a diagnosis to be made in many patients who would have otherwise undergone more invasive procedures. The diagnostic confidence, evaluated on a numerical rating scale (0-100) increased from 25.2 +/- 22.8% (prevalue) to 77.7 +/- 22.2% after Levovist (mean value +/- standard deviation, as calculated for a subgroup of 513 patients). Repeated i.v. injections were well tolerated. No specific risk was found for patients in any disease group.
Contrast Media↗
Efficacy SH U 508 A (Levovist) as blood pool enhancer in the Doppler evaluation of multiple vascular regions.
SH U 508 A (Levovist) as a blood pool enhancer to investigate multiple vascular regions with Doppler ultrasonography. Thirty patients with sub-optimal cardiac or peripheral vascular Doppler exams received 75 intravenous contrast bolus injections in all to investigate the intensity and the duration of Doppler signal enhancement after the i.v. administration of an echo contrast agent - i.e., SH U 508 A (Levovist) by Schering AG, Berlin, Germany. All cases exhibited Doppler enhancement and the investigator's "diagnostic confidence" increased from 35% (precontrast) to 91% (post-contrast) (p < 0.05). Audio Doppler intensity was measured quantitatively and more than 16 dB enhancement was demonstrated in all the vascular regions under investigation (p < 0.05). Enhancement lasted more than 60 seconds in the peripheral vessels and 120 seconds in the heart vessels. No clinically relevant adverse reactions were ever observed. To conclude, i.v., -administered SH U 508 A (Levovist) is a valuable means of increasing cardiac, femoral arterial and transcranial (cerebral arterial) Doppler signal intensity. Enhancement is durable and improves the clinical diagnostic confidence in the patients with suboptimal Doppler findings.
Adult↗