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PubMed2002

Study of coronary flow reserve with intravenous use of microbubbles (contrast echocardiography) and adenosine: protocol for clinical application in patients suspected of having coronary heart disease.

OBJECTIVE: To test the feasibility, safety and accuracy of the adenosine protocol in the study of myocardial perfusion with microbubbles contrast echocardiography. METHODS: 81 pts (64 male, 60+11 years) were submitted to contrast echocardiography with PESDA (sonicated solution of albumin 20%-1ml, dextrose 5%-12ml and deca-fluorobutane gas-8ml) to study the myocardial perfusion at rest and after bolus injection of adenosine (6 to 18mg) and to coronary angiography within 1 month each other. For each patient 3 left ventricle perfusion beds were considered (total of 243 territories). 208 territories were analyzed and 35 territories were excluded. PESDA was continuously infused (1-2ml/min), titrated for best myocardial contrast. Triggered (1:1) second harmonic imaging was used. RESULTS: Coronary angiography showed 70 flow limiting (> 75%) lesions and 138 no flow limiting lesions. At rest an obvious myocardium contrast enhancement was seen in at least 1 segment of a territory in all patients. After adenosine injection an unquestionable further increase in myocardial contrast was observed in 136 territories (99%) related to no flow limiting lesions, lasting < 10 s, and a myocardial perfusion defect was detected in 68 territories (97%) related to flow limiting lesions. It was observed only 4 false results. There were no serious complications. CONCLUSION: Myocardial perfusion study with PESDA and adenosine protocol is a practical, safe and accurate method to analyze the coronary flow reserve.

Adenosine↗
PubMed2003

Prediction markers for respiratory distress syndrome: evaluation of the stable microbubble test, surfactant protein-A and hepatocyte growth factor levels in amniotic fluid.

Surfactant treatment in infants with respiratory distress syndrome (RDS) has decreased neonatal mortality. With the advent of this therapy, it has become important to predict accurately the fetal lung maturity of a fetus before delivery. We evaluated the stable microbubble test (SMT), surfactant protein-A (SP-A) and hepatocyte growth factor (HGF) in amniotic fluid as predicting markers for RDS. Of 55 amniotic fluid samples obtained by amniocentesis from women less than 37 weeks pregnant, the SMT values were as follows: sensitivity 76.5%, specificity 84.2%, positive predictive value 68.4%, negative predictive value 88.9% and overall accuracy 81.8%. For SP-A, the values were 88.2%, 65.8%, 53.6%, 92.6% and 72.7%, respectively. If we used both SMT and SP-A, we could diagnose with 100% accuracy that a case with measurements of SMT > or = 2 and SP-A > or = 420 ng/ml would not complicate with RDS (24/24). However, the RDS diagnostic accuracy of HGF does not equal to those of SMT and SP-A levels. We concluded that the rapidity, simplicity and reliability of SMT was very useful during 24-36 weeks of gestation as a bedside procedure to predict fetuses likely to develop RDS. We also noted the additive effect of SP-A in improving the accuracy of lung maturity diagnosis.

Amniotic Fluid↗
PubMed1992

Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors.

Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions.

Carbon Dioxide↗
PubMed2001

Detection of parenchymal abnormalities in acute pyelonephritis by pulse inversion harmonic imaging with or without microbubble ultrasonographic contrast agent: correlation with computed tomography.

The purpose of this study was to evaluate the ability of pulse inversion harmonic imaging with or without microbubble ultrasonographic contrast agent in depicting renal parenchymal changes in acute pyelonephritis. The study population included 30 patients with acute pyelonephritis and 10 healthy volunteers. Pulse inversion harmonic imaging with or without contrast agent was compared with conventional ultrasonography and tissue harmonic imaging in terms of detection and conspicuity of renal abnormalities. The detection and conspicuity of renal parenchymal abnormalities in acute pyelonephritis on tissue harmonic imaging, pulse inversion harmonic imaging, and contrast-enhanced pulse inversion harmonic imaging were significantly better than those on conventional ultrasonography. In 2 of 10 healthy volunteers all 4 techniques yielded false-positive diagnoses of parenchymal abnormalities. In conclusion, tissue harmonic imaging and pulse inversion harmonic imaging are sensitive techniques for depicting renal parenchymal lesions in acute pyelonephritis. Despite relatively lower specificities and negative predictive values, these techniques are thought to be useful for the depiction of subtle parenchymal changes in acute pyelonephritis.

Acute Disease↗
PubMed2004

[Differential patterns of contrast enhancement in different focal liver lesions after injection of the microbubble US contrast agent SonoVue].

PURPOSE: To identify differential contrast enhancement patterns in different focal hepatic lesions after injection of the microbubble contrast agent SonoVue using high or low acoustic power imaging. MATERIAL AND METHODS: Forty-seven focal hepatic lesions (1-8 cm) were detected in 45 patients at unenhanced gray-scale ultrasound (US) and evaluated by color Doppler (CD) US with spectral analysis of tumoral vessels. Lesions were subsequently evaluated by US contrast specific modes after IV bolus administration of 2,4-4,8 ml of SonoVue, by intermittent high acoustic power (18 patients) or by continous low acoustic power imaging (27 patients), during arterial, portal and late phase. Subjective evaluation of lesions appearance before and after SonoVue injection was performed. For final diagnosis multiphasic helical CT (21 patients) and/or fine needle US guided biopsy (24 patients) were considered as the reference procedures. RESULTS: Final diagnoses comprised 22 hepatocellular carcinomas (HCCs; 1,5-6 cm), 2 macroregenerative nodules (RNNs; 1-2 cm), 10 metastasis (2-3,5 cm), 10 hemangiomas (2-6 cm) and 3 focal nodular hyperplasias (FNHs; 1-3 cm). On CD evaluation HCCs revealed peripheral basket shaped (12/22) or intranodular (10/22) arterial pattern while, after SonoVue injection HCCs revealed diffuse contrast enhancement during arterial phase with contrast washout during portal and late phase. Metastases did not reveal flow signals on CD or contrast enhancement after SonoVue injection, except for 2 metastases which revealed peripheral and central vessels on CD and a diffuse contrast enhancement during arterial phase, appearing hypoechoic to the adjacent liver during portal and late phase. RNNs revealed dotted contrast-enhancement during portal and late phase with isoechoic appearance to the adjacent liver. Hemangiomas revealed some peripheral venous flows on CD and a peripheral nodular contrast enhancement during arterial phase with a centripetal fill-in during portal and late phase. FNHs revealed low resistance peripheral or central arterial vessels and a diffuse contrast enhancement during arterial phase, preceded or not by central spoke wheel shaped contrast enhancement, and a persistent iso-hyperechogenicity during portal and late phase. CONCLUSIONS: SonoVue injection has showed to identify differential contrast enhancement patterns in different focal hepatic lesions.

Adult↗
PubMed1985

[Prenatal assessment of fetal lung maturity by the stable microbubble method--fundamental and clinical study].

Diagnostic value of RDS was investigated by the Stable Microbubble Method. When this method was applied to the tracheal fluid of fetuses in rabbit (28 days of gestation), the PV curve and lung-thoracic compliance showed mature patterns in the test results for weak, medium, and strong as compared with those for zero and very weak in which they showed an immature pattern. Results by this method correlated with the DSPC level in human amniotic fluid, and were little affected by the contamination of meconium or fresh plasma. Amounts of DSPC were 0.69 +/- 0.05 (mg/dl, Mean +/- SE) in zero, 1.19 +/- 0.15 in very weak, 3.99 +/- 5.06 in weak, 6.58 +/- 2.01 in medium, and 7.70 +/- 1.15 in strong test results. The coefficient of correlation was 0.56 (p less than 0.01). In the clinical study, when the mature level was arbitrarily defined as weak, the diagnostic accuracy was 76.8%, false negative rate was 0%, and false positive rate was 27.5%. If the mature level was defined as very weak, the diagnostic accuracy was 94.2% and the false positive rate was 3.4%. But the false negative rate increased to 18.8%. The diagnostic accuracy of this method was higher than the double shake test (72.2%), and was as high as the measurement of the DSPC level (92.0%).

Amniotic Fluid↗
PubMed1985

A new method for assessing right-sided heart pressures using encapsulated microbubbles--a preliminary report.

A new noncatheter method for measuring pressures of the right side of the heart uses specially manufactured microbubbles of carbon dioxide injected into the peripheral venous system. Sudden expansion of these bubbles in the cardiac chambers causes bubble oscillations at a frequency that is primarily a function of surrounding pressure. The oscillations are recordable by a microphone on the chest wall. The preliminary experience has been in dogs and further development is needed before we can begin clinical testing of the method. In its current form, the potential for measuring higher systolic pressures seems better than that for lower diastolic pressures.

Animals↗
PubMedDate not supplied

Differential diagnosis of renal lesions with US-angiography using intra-arterial CO2 microbubbles.

To differentiate renal masses, 58 patients with renal masses (39 men and 19 women, aged 23-81 years [mean age 60 years]) underwent US-angiography with intra-arterial infusion of carbon dioxide (CO2) microbubbles during conventional angiography; 32 patients had renal cell carcinomas; nine, transitional cell carcinomas; nine, renal complicated cysts; four, angiomyolipomas; two, acute focal bacterial nephritis and hematomas. Renal masses were classified into six enhancement patterns of US-angiography. Thirty-one (97%) renal cell carcinomas were histologically alveolar type and demonstrated the well-enhancement pattern. All nine renal complicated cysts showed the non-enhancement pattern. Although transitional cell carcinomas did not show definite neovascularity on conventional angiography, they were classified as the well-enhancement pattern in 4/9 (44%) and poor-enhancement pattern in 5/9 (56%) on US-angiography. Four angiomyolipomas were homogeneously enhanced. Complicated cysts were clearly differentiated from renal cell carcinomas by the enhancement pattern on US-angiography. But the differentiation between renal cell carcinomas and angiomyolipomas was difficult. US-angiography is useful for detecting fine neovascularity of renal lesions and also for the differentiation or renal cell carcinomas from complicated cysts or transitional cell carcinomas during conventional angiography.

Angiomyolipoma↗
PubMed1997

Opacification of the thoracic aorta after venous injection of sonicated albumin microbubbles. Implications for aortic dissection.

This study was designed to assess the feasibility of thoracic aorta opacification after intravenous injection of sonicated albumin microbubbles in patients with and without aortic dissection. Twenty-one patients were studied by transesophageal echocardiography. In 11 patients without aortic dissection, the opacification of the left ventricular outflow tract, aortic root and descending aorta was evaluated. Ten patients with aortic dissection were studied to assess perfusion of the true and false lumen. The left ventricular outflow tract, aortic root and descending aorta were opacified in all patients, with a systolic increase in contrast at visual analysis and at videodensitometry. The differentiation between false and true lumen was improved and was crucial in 1 case of type A chronic dissection. The intimal tear was detected in 7/9 cases by color Doppler vs 9/9 cases by contrast echocardiography. The noninvasive ultrasound opacification of thoracic aorta is feasible and may improve the diagnosis of aortic dissection.

Adult↗
PubMed1997

[Percutaneous ethanol injection therapy by ethanol mixed with CO2 microbubble for hepatocellular carcinoma].

One of the shortcomings of percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC) is that many sessions are necessary to accomplish the treatment. This may be caused by which the ultrasonography (US) image does not reflect correctly to the kinetics of injected ethanol into HCC nodule. It is considered that number of treatment sessions are able to be reduced if we just enough injected labelled ethanol under US into HCC nodule. Therefore, we tried PEIT by ethanol mixed with CO2 microbubble (CO2 ethanol). The injected CO2 ethanol was aquired as hyperechoic image without strong acoustic shadow to the end of injection. Consequently we could reduce the number of treatment sessions to almost 1 for lesions < or = 3 cm in diameter and markedly reduce total dose of injected ethanol. The detectable rate of CO2 ethanol leaked out HCC nodule was high. No serious complication occurred. There have been only 1 lesion of local recurrence and no case of intrahepatic and peritoneal dissemination for 11.5 months on average of observation after PEIT by CO2 ethanol (CO2PEIT). These findings suggest that CO2PEIT is useful method for reducing the number of treatment sessions and total dose of injected ethanol, moreover preventing complication by ethanol leakage.

Carbon Dioxide↗
PubMed1998

[Diagnosis of small hepatocellular carcinoma by US angiography with intraarterial CO2 microbubbles imaging].

US angiography, enhanced with intraarterial CO2 microbubbles imaging, documented 40 nodules of hepatocellular carcinoma (HCC) lesser than 20 mm in diameter in 34 patients, which were convinced histopathologically. As to the imaging acuity of arterial vascularity in nodules, US angiography was compared with DSA and US color angio. The detection of arterial vascularity was possible in 34 (85.0%) of 40 nodules by US angiography, 26 (65.0%) by DSA, and 28 (70.0 %) by US color angio. US angiography was available for detection of HCC, particularly with small HCC lesser than 20 mm in size.

Carbon Dioxide↗
PubMed1998

[Clinical diagnosis of pancreato-biliary lesions by ultrasound angiography with intra-arterial infusion of carbon dioxide microbubbles].

Ultrasound angiography (USAG), sonographic imaging of the blood flow with intra-arterial infusion of carbon dioxide (CO2) microbubbles, was applied to pancreato-biliary lesions. Hypervascular pattern was observed in all cases of gallbladder elevated lesions except for debris balls. However, the vascular pattern of CO2 inflow that many arterial vessels were branching off into the lesion was characteristic for gallbladder carcinomas. The hemodynamics of solid tumors of the pancreas with USAG were divided into three patterns. Most of hypovascular nodules were duct cell carcinomas, while inflammatory pancreatic masses always exhibited isovascular except for two cases of hypovascular pattern. Furthermore, islet cell tumors showed hypervascular. In cases of mucin-producing cystic tumors of the pancreas, excrescent nodules or thickened septa within the lesions were identified as hypervascular. Other cystic tumors of the pancreas also presented peculiar hemodynamics. Therefore USAG is potentially useful for detecting various vascular patterns of pancreato-biliary lesions, contributory as a diagnostic tool in this area.

Carbon Dioxide↗
PubMed2006

Is microbubble-enhanced ultrasonography sufficient for assessment of response to percutaneous treatment in patients with early hepatocellular carcinoma?

The objective of this study was to assess the efficacy of contrast-enhanced ultrasonography (CEUS) with SonoVue to evaluate the response to percutaneous treatment (ethanol injection/radiofrequency) of hepatocellular carcinoma in comparison with spiral computed tomography (CT) immediately and 1 month after treatment. Forty-one consecutive cirrhotic patients with early stage tumor (not suitable for resection) were included. Spiral CT and CEUS were performed in all patients before treatment, in the following 24 h, and 1 month later. The results of each examination were compared with the 1-month spiral CT, considered the gold standard technique. The 24-h CEUS and the 24-h spiral CT sensitivity to detect residual disease were 27% and 20%, respectively. The 24-h CEUS and the 24-h spiral CT positive predictive value of persistent vascularization detection were 75% and 66%, respectively. The 1-month CEUS detected partial responses in ten out of 11 cases (91% sensitivity, 97% specificity, 95% accuracy). Spiral CT and CEUS performed in the 24 h following treatment are slightly useful to evaluate therapeutic efficacy. The 1-month CEUS has a high diagnostic accuracy compared with spiral-CT in the usual assessment of percutaneous treatment response.

Administration, Cutaneous↗
PubMed2006

Microbubble-enhanced hemorrhage control using high intensity focused ultrasound.

Our objective was to investigate whether hemorrhage control can be achieved faster when high-intensity focused ultrasound (HIFU) is applied in the presence of ultrasound contrast agents (UCA) as compared to HIFU only application. Incisions (3 cm long and 0.5 cm deep) were produced in the livers of anesthetized rabbits. UCA Optison (0.18 ml/kg) was injected into the mesenteric vein. A HIFU applicator (5.5 MHz, 6800 W/cm2 in situ) was scanned at a rate of 1-2 mm/s in one direction over the incision (with multiple passes if needed), until hemostasis was achieved. Hemostasis times were 59+/-23 s (n=21) in the presence of Optison and 70+/-23 s (n=29) without Optison. The presence of Optison produced on average 37% reduction in hemostasis times normalized to initial bleeding rates (p<0.05), as well as 60% faster formation of the coagulum seal over the incision (p<0.05). Gross and histological observations showed similar appearance of HIFU lesions produced in the presence of Optison and HIFU lesions produced without Optison. Our results suggest potential utility of UCA for increasing efficiency of HIFU-induced hemostasis of solid organ injuries.

Albumins↗
PubMed2004

Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles.

Local blood-brain barrier (BBB) opening is an advantageous approach for targeted drug delivery to the brain. Recently, it has been shown that focused ultrasound (US) exposures (sonications), when applied in the presence of preformed gas bubbles, caused magnetic-resonance (MR) proven reversible opening of the BBB in targeted locations. The cellular mechanisms of such transient barrier disruption are largely unknown. We investigated US-induced changes in endothelial cell fine morphology that resulted in the BBB opening in rabbits. To obtain evidence for the passage of blood-borne macromolecules through the opened transvascular routes, an immunocytochemical procedure for endogenous immunoglobulinG (IgG) was performed, in addition to the routine electron microscopy. An increased number of vesicles and vacuoles, fenestration and channel formation, as well as opening of some tight junctions, were seen in capillaries after low-power (0.55 W) sonication. Immunosignals presented in some of the vesicles and vacuoles, in the cytoplasmic channels and, so rarely, in intercellular clefts; immunosignals could also be seen in neuropil around the blood vessels. Damage to the cellular ultrastructure was not seen in these areas. However, cell destruction and leakage of IgG through defects of the endothelial lining took place at 3 W sonications. The data reveals that several mechanisms of transcapillary passage are possible after such sonications: 1. transcytosis; 2. endothelial cell cytoplasmic openings--fenestration and channel formation; 3. opening of a part of tight junctions; and 4. free passage through the injured endothelium (with the higher power sonications). These findings could be considered in further development of the strategy for drug delivery to brain parenchyma.

Animals↗
PubMed2004

Effect of shell type on the in vivo backscatter from polymer-encapsulated microbubbles.

This study compared in vivo enhancement from four different polymer-encapsulated ultrasound (US) contrast agents. The agents were produced with a rigid shell composed of the biodegradable block copolymer poly[D,L-lactide-co-glycolide] (PLGA) with the lactic and glycolic acid ratios 50:50, 75:25, 85:15 and 100:0 (i.e., increasingly hydrophobic shell compositions). Approximately the same bubble diameter (1.2 microm) and concentration (0.4 g/mL) were obtained for each agent. In four rabbits, audio Doppler signals were acquired from a 10 MHz cuff transducer placed around a surgically exposed vessel (contrast dose: 0.0125 to 0.15 mL/kg). In vivo dose responses were calculated off-line (in dB). Nine rabbit kidneys were imaged during contrast administration (0.1 mL/kg) in power Doppler and grey-scale pulse inversion harmonic (PIHI) modes using an HDI 5000 scanner (Philips Medical Systems, Bothell, WA). Time-intensity curves were produced and the time-to-peak, peak intensity, slope, area under the curve (AUC) and total duration of enhancement for each agent were compared. All agents produced marked Doppler enhancement with increasing duration from the 50:50 agent (48 +/- 10 s) to the 75:25 agent (166 +/- 46 s), the 85:15 agent (403 +/- 83 s) and with the 100:0 agent (603 +/- 93 s) lasting longest (p < 0.02). No other parameters changed significantly, except the AUC of the 85:15 agent, which was greater than that of the 50:50 agent (190.75 vs. 61.58; p = 0.02). The in vivo dose-response curves were similar for all agents, with mean enhancement up to 20.6 +/- 1.11 dB (p = 0.17). In conclusion, contrast duration increases by an order of magnitude as the lactic acid component in the polymer-encapsulated bubbles increases and the shell, thus, becomes increasingly hydrophobic.

Animals↗
PubMed2004

Ultrasound-induced microbubble coalescence.

We studied the interaction of ultrasound contrast agent bubbles coated with a layer of lipids, driven by 0.5 MHz ultrasound. High-speed photography on the submicrosecond timescale reveals that some bubbles bounce off each other, while others show very fast coalescence during bubble expansion. This fast coalescence cannot be explained by dissipation-limited film drainage rates. We conclude that the lipid shell ruptures upon expansion, exposing clean free bubble interfaces that support plug flow profiles in the film and inertia-limited drainage whose time scales match those of the observed coalescence.

Contrast Media↗