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Biomedical subjects

R Schlief

Publications and source records attributed to R Schlief.

At least 19 recordsLinked to original sources

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

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

Quantitative echo contrast concentration measurement by Doppler sonography.

The hypothesis investigated in this study is that Doppler ultrasound can be used to make quantitative echo contrast concentration measurements in flow systems. Our motivation was to demonstrate the utility and some of the pitfalls of using scattered ultrasound intensity to quantify echo contrast in chambers and vessels. Doppler ultrasound was used rather than conventional imaging techniques because of its natural association with the assessment of flow in chambers and vessels. We compared the intensity of audio Doppler to various steady-state concentrations echo contrast in a carefully controlled in vitro flow system. A total of 62 paired audio Doppler intensity and echo contrast concentration measurements were made. A weak positive correlation was found between the absolute echo contrast concentration and audio Doppler intensity (r = 0.510, p = 0.001). The correlation was weak because of the many unknowns and effervescent nature of microbubble echo contrast agents. However, audio Doppler intensity was shown to correlate strongly with the relative concentration of echo contrast over short time periods (r = 0.958, p = 0.0001). The results show that Doppler intensity can be used to quantitatively measure the relative, but not the absolute concentration of echo contrast in in vitro flow systems.

Contrast Media

Volumetric arterial flow quantification using echo contrast. An in vitro comparison of three ultrasonic intensity methods: radio frequency, video and Doppler.

The two hypotheses presented in this paper are: (1) absolute and relative volumetric flow rates in vessels can be measured by echo contrast time-intensity curves; and (2) echo contrast time-intensity curves generated by different ultrasound backscatter intensity techniques have equivalent capability for flow measurements. A nonpulsatile flow system was built for quantitative ultrasound backscatter measurements from bolus echo contrast injections using two different volumes of mixing. A total of 49 echo contrast bolus injections were made at various flow rates (0.44-2.59 L/min). Ultrasound backscatter time-intensity curves were generated by ultrasound radio frequency, video and Doppler techniques. The rate of backscattered ultrasound intensity washout for each technique (WASHOUT RATE), and relative change in WASHOUT RATE (delta WASHOUT RATE) were compared to the volumetric flow rate (FLOW) and changes in flow rate (delta FLOW), respectively. The relationship between WASHOUT RATE, FLOW and the volume of contrast mixing was studied. A linear relationship was demonstrated between WASHOUT RATE and delta WASHOUT RATE and the corresponding FLOW and delta FLOW by all three methods (r > 0.90 for all comparisons). The WASHOUT RATE was found to depend on the FLOW and the volume of contrast mixing, but the delta WASHOUT RATE was equal to the delta FLOW and independent of the volume of mixing. Time-intensity curves can be generated from different ultrasound backscatter intensity techniques and the WASHOUT RATE correlates well with FLOW. delta FLOW can be determined directly from the corresponding delta WASHOUT RATE. Doppler ultrasound, because of its natural association with the assessment of flow in chambers and vessels, is uniquely suited to assessment of arterial volumetric blood flow in vitro.

Arteries

Enhancement of mitral regurgitation and normal left atrial color Doppler flow signals with peripheral venous injection of a saccharide-based contrast agent.

OBJECTIVES: The saccharide ultrasound contrast agent SHU 508 A was used to test the hypothesis that an intravenous, transpulmonary contrast method can enhance color Doppler flow signals in the left atrium in a clinically useful manner. BACKGROUND: Color Doppler display of mitral regurgitation may be unreliable because of variable signal to noise ratios that are at times poor. Traditional contrast agents enhance color Doppler flow signals in the right heart chambers. This study describes our observation of a recently developed contrast agent, SHU 508 A, capable of pulmonary transit after peripheral venous injection. METHODS: Control subjects (n = 10) and patients with suspected mitral regurgitation (n = 23) were studied by color Doppler flow imaging before and after 3-g intravenous doses of SHU 508 A. Reference grading of mitral regurgitation (0 to 3) was formulated from left ventricular angiography. In the four-chamber view of the left atrium, we selected for analysis the systolic frame with the maximal retrograde jet of mitral regurgitation (aliased/blue) and the diastolic frame with the maximal color coding from anterograde pulmonary venous flow (red) for planimetry and for grading the intensity of the color Doppler signal (0 to 5). RESULTS: The score of the color Doppler signal intensity increased by > or = 2.5 after 3 g of SHU 508 A (p < 0.001). Flow detection improved, as shown by the increased jet area of mitral regurgitation (> or = 170%), after 3 g of SHU 508 A (3 +/- 3 vs. 12 +/- 8 cm2, p < 0.001) and by a > or = 200% increase in normal anterograde flow area (p < 0.001) in both the mitral regurgitation group and the control group. After contrast enhancement, the correlation between angiographic grading and the relation of jet area to the left atrial area increased from r = 0.79 to r = 0.91. CONCLUSIONS: Contrast-mediated increased echogenicity of the left atrial blood pool improves the signal to noise ratio of Doppler images of mitral regurgitation and anterograde atrial flow. The technique is safe and simple and seems to minimize variability due to instrument design and anatomic signal attenuation.

Adult

Contrast-enhanced transcranial Doppler US with a new transpulmonary echo contrast agent based on saccharide microparticles.

The purpose of this first patient study (phase II) was to evaluate the clinical usefulness of a new echo contrast agent at transcranial Doppler ultrasonography (US). Twenty patients were selected from a group of 242 patients undergoing conventional transcranial Doppler US who had low (n = 18) or absent (n = 2) Doppler signals from the middle cerebral artery (MCA). The extent and duration of Doppler signal increase was measured in 30 MCAs and in 14 basilar arteries following the intravenous injection of a transpulmonary galactose microparticle suspension (SH U 508 A) at three concentrations (200, 300, and 400 mg/mL). Doppler waveform analysis became possible in 93% (28 of 30) of the MCAs following injection. The maximal increase in average Doppler signal intensity (11 dB at 200 mg/mL, 15 dB at 300 mg/mL, and 17 dB at 400 mg/mL) and the increase in average duration of the signal enhancement (163 seconds at 200 mg/mL, 219 seconds at 300 mg/mL, and 240 seconds at 400 mg/mL) depended on contrast agent concentration. Doppler waveform analysis became possible in 79% (11 of 14) of the basilar arteries. The intravenous injection of this new echo contrast agent markedly increases Doppler signal intensity in patients with nondiagnostic results at conventional Doppler US.

Basilar Artery

A transpulmonary contrast medium enhances the transcranial Doppler signal in humans.

BACKGROUND AND PURPOSE: Transtemporal insonation in transcranial Doppler sonography is often impaired by an insufficient signal-to-noise ratio, especially in elderly patients. A transpulmonary stable air microbubble suspension was injected intravenously in humans as an intracranial ultrasonic contrast agent. METHODS: In a clinical phase II study, 20 patients (15 women, 5 men; mean age, 65.5 +/- 11.5 years) presenting with clinical indications for transcranial Doppler investigation were examined. A total of 97 intravenous injections with different concentrations (200, 300, and 400 mg/mL of suspension) of air microbubbles bound to galactose microparticles as a carrier were performed. The signal enhancement of color-coded pulse curves of basal cerebral arteries was evaluated off-line in comparison to an integrated color-coded decibel scale, considering quality, quantity, and time course of enhancement requiring a 3-dB level above the native signal. The overall diagnostic information was assessed according to a reliability score. RESULTS: The first acoustic signal increase was registered after an average of 21 seconds. Time intervals for a dose-dependent peak intensity and maximal duration were 41.3 +/- 17.1 seconds and 118.0 +/- 69.8 seconds (200 mg/mL); 55.5 +/- 27.7 seconds and 237.0 +/- 112.3 seconds (300 mg/mL); and 66.1 +/- 31.8 seconds and 293.0 +/- 122.0 seconds (400 mg/mL), respectively. Duration of signal enhancement increased significantly (P < .05) with higher concentrations. The extent of signal enhancement during the whole pulse curve reached an average of 9.1 +/- 5.0 dB for 200 mg/mL, 12.0 +/- 5.4 dB for 300 mg/mL (significant on P < .05 level), and 13.1 +/- 5.6 dB for 400 mg/mL concentration (P = NS). Respective maximal intensity spots reached 17.5 +/- 6.0, 20.7 +/- 5.5, and 22.7 +/- 5.9 dB for increasing concentrations, respectively. Overall visual assessment of enhanced pulse curves for diagnostic reliability showed a sufficient result in 38.1% of all injections with 200 mg/mL, in 88.6% with 300 mg/mL, and in 84.2% with 400 mg/mL concentration. Minimal side effects occurring in 12.4% of all injections were all reversible. CONCLUSIONS: Transpulmonary stable air microbubbles bound to a galactose carrier represent a useful and safe contrast agent in case of an insufficient native signal in transcranial Doppler investigation.

Adult