Microbubble contrast agents: a new era in ultrasound.
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Carcinoma, Hepatocellular↗
Biomedical subjects
D O Cosgrove
Publications and source records attributed to D O Cosgrove.
Developments in ultrasound contrast media.
Ultrasound microbubble contrast agents are effective and safe echo enhancers. An ingenious array of methods are employed to achieve stability and provide a clinically useful enhancement period. Microbubbles enhance ultrasound signals by up to 25 dB (greater than 300-fold increase) due to resonant behaviour. This is used to rescue failed Doppler studies and may be extended to image the microcirculation of tumours and the myocardium using non-linear modes. Functional studies open up a whole range of applications by using a variety of active and passive quantitation techniques to derive indices from the transit of contrast through a tissue of interest. This has been especially successful in the detection of liver metastases and cirrhosis and shows great promise as a clinical tool. It also has great potential in measuring microcirculatory flow velocity. The demonstration that some microbubbles are not just pure blood pool agents but have a hepatosplenic specific phase has extended the versatility of ultrasound. Imaging of this stationary phase with non-linear modes such as phase inversion and stimulated acoustic emission, has improved the sensitivity and specificity of ultrasound in the detection and characterisation of focal liver lesions to rival that of CT and MR.
Contrast Media↗
Development of three-dimensional power Doppler ultrasound imaging of fetoplacental vasculature.
To develop an off-line system for three-dimensional (3-D) ultrasound (US) reconstruction of fetoplacental vasculature using colour segmentation and reconstruction software and to determine sources of error in fully freehand ultrasound image acquisition. US images were acquired freehand with the Acuson Sequoia (5C 2-MHz transducer) using power Doppler. After digital transfer to a personal computer, CQ Analysis software (Kinetic Imaging Ltd, Liverpool, UK) was used to segment the colour information from these images, and the resulting 8-bit grey-scale images were used for 3-D rendering using commercial software (VoxBlast, Vaytek Inc., Fairfield, IA, USA). 2-D scanning, software and freehand acquisition accuracy were assessed using a linear test rig and distance and volume phantoms (Dansk Phantom Service Ltd); 2-D scanning accuracy was within 1.3%, and software reconstruction accuracy within 1% for x and y planes and up to 3% for the z plane. Fully freehand acquisition was associated with a 12% to 18% mean percentage error in distance measurement in the plane of acquisition. Volumetric reconstruction inaccuracy was between 1.5% and 19.7% for precisely separated images and between 16.2% and 39.2% for fully freehand image acquisition. Rendered 3-D US vascular images clearly delineated vascular anatomy within the placenta and cord. Fully freehand 3-D US does have a role in off-line reconstruction of vascular anatomy, although variability in the z plane precludes its use for volumetric measurement. (E-mail: a.welsh@ic.ac.uk)
Female↗
Do different types of liver lesions differ in their uptake of the microbubble contrast agent SH U 508A in the late liver phase? Early experience.
PURPOSE: To compare the uptake of SH U 508A in different types of liver lesions by using stimulated acoustic emission. MATERIALS AND METHODS: Thirty-seven patients with characterized lesions (metastasis, n = 17; hepatocellular carcinoma, n = 4; hemangioma, n = 9; focal nodular hyperplasia, n = 7) received 2.5 g SH U 508A. After 5 minutes, stimulated acoustic emission was elicited by using a previously described method. Liver and/or lesional differences were assessed with videodensitometry (objective conspicuity score), and two observers assessed each lesion by using a six-point scale (subjective conspicuity score). RESULTS: Metastases and hepatocellular carcinoma had low stimulated acoustic emission; median objective conspicuity scores were 70% and 68% (all scores were > or =43%), respectively, and subjective conspicuity scores were 2 or higher for both observers. Hemangiomas had reduced stimulated acoustic emission, with more variability; the median objective conspicuity score was 41% (range, 9%-72%), and the median subjective conspicuity scores were 2 (range, 1-4) and 3.5 (range, 1-5) for observers 1 and 2, respectively. Focal nodular hyperplasia had stimulated acoustic emission comparable to that of the liver in all cases; the median objective conspicuity score was -4.7% (all scores were <6%), and the subjective conspicuity score was 1 or lower for both observers. This finding completely separated focal nodular hyperplasia and malignancies. Significant differences were seen between focal nodular hyperplasia and all other lesion types (P < .05). CONCLUSION: Strong late-phase lesional uptake of SH U 508A is characteristic of focal nodular hyperplasia, is seen in some hemangiomas, and was not observed in malignancies.
Adult↗
Pulse-inversion mode imaging of liver specific microbubbles: improved detection of subcentimetre metastases.
Pulse-inversion mode (a new ultrasound mode) can be used to image the late liver-specific parenchymal phase of the microbubble contrast-agent Levovist. Scanning in pulse-inversion mode after Levovist improves the detection of liver metastases and reveals more lesions of smaller size than conventional ultrasonography and computed tomography.
Colorectal Neoplasms↗
Sonography of palpable breast cancer.
PURPOSE: Because of the increasing use of sonography to rule out cancer in women with palpable breast abnormalities, this study was performed to determine the rate of sonographically occult malignancy in this clinical setting. METHODS: Women who were recommended for biopsy based on mammographic and/or clinical findings underwent breast sonography. This study retrospectively analyzed the subset of patients with palpable malignant lesions. Lesions were classified as visible or occult on mammography and sonography. Patients without a tissue diagnosis of tumor were excluded. RESULTS: Of 1,346 masses that underwent biopsy or aspiration, 616 lesions were palpable, and of these, 293 were malignant. Sonography detected all 293 palpable malignant lesions (95% confidence interval for sensitivity, 99-100%). Eighteen lesions were mammographically occult. The median lesion size as determined by sonography was 1.8 cm; for the lesions that were mammographically occult, the median size was 1.6 cm. The most common histopathologic diagnosis for both groups of lesions was infiltrating ductal carcinoma. CONCLUSIONS: All palpable malignant breast lesions were visible by sonography in patients in whom a biopsy was recommended. However, we caution that until the false-negative rate of sonography for equivocal palpable abnormalities is determined prospectively, sonography cannot be accurately applied to rule out malignancy in this setting.
Adolescent↗
Ex vivo delineation of placental angioarchitecture with the microbubble contrast agent Levovist.
OBJECTIVE: The aim of this study was to delineate placental vasculature with the microbubble contrast agent Levovist (99.9% galactose and 0.1% palmitic acid; Schering AG, Berlin, Germany), with the ultimate goal of delineating placental vascular anatomy in utero. STUDY DESIGN: A placental lobule from each of 11 term human placentas was perfused on the fetal side of the circulation under physiologic conditions. Randomly assigned dose-concentration combinations of Levovist were administered through a chorionic artery into the corresponding placental lobule, and the resultant echoenhancement with power Doppler imaging was recorded for digital analysis. Interplacental variability was corrected for by averaging the results of three injections at each dose-concentration combination. RESULTS: Echoenhancement was seen at all dose-concentration combinations in the injected lobule but not in adjacent control lobules. The three dose-concentration combinations that achieved optimal maximal integrated intensity and duration of action for both chorionic vessel and villus enhancement were 100 microL/kg of 400-mg/mL Levovist, 200 microL/kg of 400-mg/mL Levovist, and 400 microL/kg of 200-mg/mL Levovist. CONCLUSION: Microbubble contrast injection into the fetal vasculature enabled power Doppler imaging echoenhancement both in chorionic vessels and within the villus tree. We speculate that fetal injection of contrast agent may be applied to the delineation of placental lesions or areas of interfetal transfusion, although its applicability will be hindered by the need for fetal blood sampling.
Blood Vessels↗
Ultrasonographic contrast media in the urinary tract.
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Contrast Media↗
[Stimulated acoustic emissions with the ultrasound contrast medium levovist: a clinically useful contrast effect with liver-specific properties].
PURPOSE: The purpose of this study was systematically to investigate stimulated acoustic emission (SAE) with the microbubble contrast agent Levovist (Schering AG, Berlin) in vivo with regards to reproducibility, distribution in various organs over time, dependence on technical factors, and influence on the delineation of focal liver lesions. PATIENTS AND METHODS: 2 intravenous injections of 1 g of Levovist were given to 2 dogs and 1-6 injections of 2.5 g Levovist to 5 healthy volunteers and 37 patients. The liver, spleen, large abdominal vessels, and kidney were intermittently scanned for up to 30 min. Studies were evaluated for the presence of SAE signals by 2 observers. In 20 patients with focal liver lesions (15 with metastases, 4 haemangiomata, 1 hepatocellular carcinoma, and 1 cyst) the influence on lesion visualization was also assessed. RESULTS: SAE effects, lasting up to 30 minutes, were seen in all subjects in the liver and spleen. Vascular and renal SAE signals were noted shortly after injection, lasting up to 6 minutes. SAE was absent or markedly reduced in focal liver lesions, which were seen as colour voids. This increased the conspicuity of focal lesions, and in 5 patients additional metastases were detected that could not be delineated on B-mode alone. CONCLUSION: A liver- and spleen-specific late phase of Levovist can be consistently demonstrated using SAE and the effect increases the conspicuity of focal liver lesions.
Adult↗
[Comparison of bolus and infusion of the ultrasound contrast media levovist for color doppler ultrasound of renal arteries].
PURPOSE: To investigate if the duration of Doppler enhancement of the ultrasound contrast agent Levovist can be prolonged by continuous infusion compared to bolus injections in patients. METHODS: 12 patients with suspected renal artery stenosis were included. Each patient received 1 or 2 bolus injections of 4 g each and a "fast" infusion of 3 ml/min (average dose: 7 g) of Levovist. In 8 patients an additional "slow" infusion of 1 ml/min (average dose 4.2 g) was given. The duration of "strong" Doppler signal enhancement and the visualization of vessels were compared. RESULTS: The duration of strong enhancement was substantially prolonged by the slow infusion (bolus 6:21 min, fast infusion: 8:57 min, slow infusion: 15:12 min, p < 0.001). The dose effectiveness (duration of strong enhancement per 1 g Levovist) was markedly improved from 0:57 min (bolus) to 3:36 min (slow infusion). Visualisation of the renal arteries was more complete with the slow infusion. CONCLUSION: Levovist infusions at 1 ml/min are superior to bolus injections in the assessment of renal arteries. They prolong the enhancement, make more efficient use of a given dose of contrast material and thus allow additional clinically relevant information to be obtained at reduced cost.
Adult↗
Twin fetuses: intravascular microbubble US contrast agent administration--early experience.
PURPOSE: To explore the feasibility of administering SH U 508A by using a single-needle procedure at ultrasonography (US) in twin pregnancies to confirm interfetal transfusion in monochorionic twins and delineate placental angioarchitecture in pregnancies with twin-twin transfusion syndrome. MATERIALS AND METHODS: Fourteen twin pregnancies were studied over 12 months: seven with monochorionic twins, including six with twin-twin transfusion syndrome; two of unknown chorionicity; and five with known dichorionic twins discordant for fetal karyotype or anomaly and undergoing selective feticide in the third trimester. Bolus injection of 100 microL/kg of estimated fetoplacental weight of 400 mg/mL of SH U 508A was performed in the intrahepatic vein of one twin, and evidence of interfetal transfusion was sought by means of digital analysis of power Doppler signals in the contralateral twin. RESULTS: Contralateral twin echo enhancement was seen in four of the nine ultimately histopathologically proved monochorionic twins. As expected, no evidence of echo enhancement in the contralateral twin was seen in any of the five dichorionic twin pregnancies. There was no evidence of fetal compromise associated with the procedure. CONCLUSION: These pilot results suggest that microbubbles can be used to demonstrate interfetal transfusion but not to delineate placental vascular anatomy.
Adult↗
Liver lesions: intermittent second-harmonic gray-scale US can increase conspicuity with microbubble contrast material-early experience.
The authors investigated the effect of intermittent second-harmonic gray-scale (ISHGS) ultrasonography (US) with SH U 508A microbubbles on the conspicuity of focal liver lesions. Twenty-three patients were included in the study. Images were analyzed subjectively and quantitatively. Objective lesion conspicuity was increased. In 12 of the 15 patients with liver malignancy, gray-scale defects were seen in previously unsuspected areas. ISHGS US may improve the sensitivity of US for liver lesions.
Adult↗
Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A-early experience.
Twenty consecutive patients with known liver malignancies underwent ultrasonography (US) in conventional B mode and in pulse-inversion mode in the late hepatic-specific parenchymal phase after intravenous administration of SH U 508A, a microbubble US contrast agent. Two experienced readers assessed subjective and objective conspicuity, number of lesions, and smallest lesion diameter in each mode. Subjective and objective conspicuity were improved with pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode than with conventional B mode, improving the detection of metastases less than 1 cm in size.
Adult↗
Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent.
BACKGROUND: Hepatic cirrhosis is accompanied by several haemodynamic changes including arterialisation of the liver, intrahepatic shunts, pulmonary arteriovenous shunts, and a hyperdynamic circulatory state. We postulated that the hepatic first pass of a bolus of an ultrasound contrast agent injected into a peripheral vein is accelerated in patients with cirrhosis. We investigated this first pass in patients with diffuse liver disease and in normal controls to assess whether it provides useful differential diagnostic information. METHODS: We enrolled 15 patients with biopsy-proven cirrhosis, 12 patients with biopsy-proven non-cirrhotic diffuse liver disease, and 11 normal controls. We carried out continuous spectral doppler ultrasonography of a hepatic vein from 20 s before to 3 min after a peripheral intravenous bolus injection of 2.5 g Levovist. The intensity of the doppler signal was measured and used to plot time-intensity curves. FINDINGS: Patients with cirrhosis showed a much earlier onset of enhancement (arrival time; mean 18.3 s) and peak enhancement (mean 55.5 s) than controls (49.8 s and 97.5 s) or patients with non-cirrhotic diffuse liver disease (35.8 s and 79.7 s). All patients with cirrhosis had an arrival time of the bolus of less than 24 s, whereas the arrival time was 24 s or more in 22 of the 23 other participants. Peak enhancement was higher in patients with cirrhosis (mean 48.7 units) than in the other two groups (12.5 and 12.3 units, respectively). We found highly significant differences between the patients with cirrhosis and each of the other two groups for all variables (p<0.005), whereas we found no significant differences between non-cirrhotic patients and controls. INTERPRETATION: Our preliminary study suggests that analysis of liver transit time of a bolus of ultrasound contrast agent provides useful information about haemodynamic changes in patients with cirrhosis. Measurement of the arrival time of the bolus allows discrimination of patients with cirrhosis from controls and from patients with non-cirrhotic diffuse liver disease, and has potential as a non-invasive test for cirrhosis.
Adult↗
Transit-time studies with levovist in patients with and without hepatic cirrhosis: a promising new diagnostic tool.
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Adult↗
Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease.
Quantitative studies were performed to investigate liver- specific uptake of the microbubble Levovist, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow-moving. These comprised studies of biodistribution comparing the liver and kidney in five normal volunteers, reproducibility in 34 patients, comparison between cirrhotics and controls (n = 9 each) and maximal depth of effect at different frequencies (180 measurements in 31 patients). Stimulated acoustic emission lasted beyond 30 min, with strongly liver-specific properties in each volunteer and was highly reproducible. No difference in the amount of SAE in the superficial liver was seen between cirrhotic and normal livers, but attenuation was higher in cirrhotics. This demonstrates a frequency-dependent effect on liver SAE penetration. We conclude that the liver uptake of Levovist lasts over 30 min, is reproducible, occurs even where diffuse liver disease is present and can be used to assess tissue attenuation in a novel fashion.
Adult↗
Improved imaging of liver metastases with stimulated acoustic emission in the late phase of enhancement with the US contrast agent SH U 508A: early experience.
PURPOSE: To see whether stimulated acoustic emission (SAE) in the liver parenchyma in the late phase of enhancement with SH U 508A increases the conspicuity of occult metastases at ultrasonography (US). MATERIALS AND METHODS: Eighteen patients with known hypo- or hypervascular hepatic metastases underwent US after SH U 508A administration, after a delay of at least 5 minutes, to ensure decay of blood pool enhancement. In 16 patients with visible metastases, conspicuity was compared on registered SAE and gray-scale scans by two blinded readers and by using computerized analysis of relative gray-scale and color Doppler conspicuity scores inside and outside the lesion. In nine patients, areas suspected of being involved but without definite gray-scale masses were imaged in the same way. Paired sections were analyzed by two blinded readers looking for parenchymal color defects without corresponding gray-scale masses; nine control images from three healthy volunteers were also included. RESULTS: Intense, transient parenchymal SAE was seen in all subjects. All metastases appeared as areas of reduced or absent signal. The conspicuity score was 80% for SAE versus 9% for gray-scale US (P < .001, Wilcoxon signed rank test). SAE-specific defects were seen in all patients but in none of the volunteers. Metastases seen on SAE but undetectable on gray-scale images were proved in three patients. CONCLUSION: SAE with SH U 508A improves the conspicuity of metastases. SAE-specific defects may reveal isoechoic or subtle metastases.
Biopsy↗