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PubMedDate not supplied

Focal hepatic lesions: contrast-enhancement patterns at pulse-inversion harmonic US using a microbubble contrast agent.

OBJECTIVE: To analyze the contrast-enhancement patterns obtained at pulse-inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine tumor vascularity and the acoustic emission effect. MATERIALS AND METHODS: We reviewed pulse-inversion images in 90 consecutive patients with focal hepatic lesions, namely hepatocellular carcinoma (HCC) (n=43), metastases (n=30), and hemangioma (n=17). Vascular and delayed phase images were obtained immediately and five minutes following the injection of a microbubble contrast agent. Tumoral vascularity at vascular phase imaging and the acoustic emission effect at delayed phase imaging were each classified as one of four patterns. RESULTS: Vascular phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of metastases, and peripheral nodular enhancement in 71% of hemangiomas. Delayed phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic, decreased enhancement in 93% of metastases; and hypoechoic and reversed echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement patterns were associated with a specificity of 91% or greater, and 92% or greater, respectively, and with positive predictive values of 71% or greater, and 85% or greater, respectively. CONCLUSION: Contrast-enhancement patterns depicting tumoral vascularity and the acoustic emission effect at PIHI can help differentiate focal hepatic lesions.

Adult↗
PubMed2006

Microbubble-enhanced ultrasound exposure improves gene transfer in vascular endothelial cells.

AIM: To explore the effects of ultrasound exposure combined with microbubble contrast agent (SonoVue) on the permeability of the cellular membrane and on the expression of plasmid DNA encoding enhanced green fluorescent protein (pEGFP) transfer into human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs with fluorescein isothiocyanate-dextran (FD500) and HUVECs with pEGFP were exposed to continuous wave (1.9 MHz, 80.0 mW/cm(2)) for 5 min, with or without a SonoVue. The percentage of FD500 taken by the HUVECs and the transient expression rate of pEGFP in the HUVECs were examined by fluorescence microscopy and flow cytometry, respectively. RESULTS: The percentage of FD500-positive HUVECs in the group of ultrasound exposure combined with SonoVue was significantly higher than that of the group of ultrasound exposure alone (24.0% +/- 5.5% vs 66.6% +/- 4.1%, P < 0.001). Compared with the group of ultrasound exposure alone, the transfection expression rate of pEGFP in HUVECs was markedly increased with the addition of SonoVue (16.1% +/- 1.9% vs 1.5% +/- 0.2%, P < 0.001). No statistical significant difference was observed in the HUVECs survival rates between the ultrasound group with and without the addition of SonoVue (94.1% +/- 2.3% vs 91.1% +/- 4.1%). CONCLUSION: The cell membrane permeability of HUVECs and the transfection efficiency of pEGFP into HUVECs exposed to ultrasound are significantly increased after addition of an ultrasound contrast agent without obvious damage to the survival of HUVECs. This non-invasive gene transfer method may be a useful tool for clinical gene therapy of hepatic tumors.

Cells, Cultured↗
PubMedDate not supplied

[Interaction between microbubbles and ultrasound. Present and future applications of contrast agents].

The way in which microbubbles (MB) increase the acoustic signal of blood was discovered incidentally during a hemodynamic study 30 years ago. Since then, new techniques and materials have been developed, looking for possible applications. Stability of MB has been increased, their size has been diminished, and interactions between MB and ultrasound have been understood. In this paper, we show the ways in which MB have been demonstrated or, at least, suggested to be useful in the fields of cardiological diagnosis and treatment.

Contrast Media↗
PubMed2006

Radiofrequency ablation of liver tumors: the role of microbubble ultrasound contrast agents.

Radiofrequency ablation (RFA) is currently indicated for the treatment of primary and metastatic hepatic malignancies. Real-time ultrasound (US) is generally used during the procedure to guide electrode placement, but for evaluating the results of treatment, contrast-enhanced computed tomography and magnetic resonance imaging have traditionally been considered more effective. This view has changed, however, with the recent development of contrast-enhanced ultrasound (CEUS) (eg, using sulfur hexafluoride microbubbles), which can provide valuable information on the effects of RFA more rapidly and economically than computed tomography or magnetic resonance imaging without exposing the patient to ionizing radiation. In our center, CEUS is performed in patients with liver tumors before and immediately after RFA, in selected cases during the procedure as well, and in the follow-up. Between January 2003 and June 2005, we performed CEUS on 350 patients scheduled for RFA of primary or metastatic liver tumors. In 14 (13.4%) of the 96 patients whose disease was metastatic, CEUS revealed lesions that had been missed on the conventional US examination. In most of these cases, the result was a more complete treatment performed under CEUS guidance. In the remaining 2 (14%) of 14, the results of the examination allowed us to avoid subjecting the patient to useless treatment. In our experience, the use of CEUS also improved the management and follow-up of patients undergoing interstitial therapy.

Catheter Ablation↗
PubMed2006

The kidney: imaging with microbubble contrast agents.

Conventional ultrasonography of the kidney is faced by limitations due to the poor contrast of B-mode imaging for parenchymal disease and limited sensitivity of color Doppler for the detection of intracortical capillaries and deep pedicular vessels. Ultrasound contrast agents (USCAs) overcome these limitations, allowing the development of new applications for renal blood flow imaging and quantification. These improvements result from the increased acoustic response obtained from the microbubbles, as well as from the development of pulse sequences for bubble-specific imaging. In radiology, the liver has been considered as the primary target for contrast because USCAs allow both detection and characterization of focal lesions. The kidney has been less studied because USCA kinetics do not provide the same obvious potential for tumor characterization, and most clinical trials for contrast-enhanced renal imaging were conducted using color Doppler. Despite this, the kidney offers promising applications as USCAs improve the detection of abnormal microvascular and macrovascular disorders. Contrast-enhanced US may become the modality of choice for diagnosis of renal artery stenosis and detection of a perfusion deficit, as well as for characterization of indeterminate renal lesions, atypical cystic lesions, and the identification of acute pyelonephritis.

Contrast Media↗
PubMed2006

[Echogenic phospholipids-based gas-filled microbubbles as delivery system of antisense oligodeoxynucleotides].

AIM: To investigate the feasibility of transfer antisense oligodeoxynucleotides (AS-ODNs) by the phospholipids-based gas-filled microbubbles (PGM) under ultrasound activation. METHODS: An antisense oligodeoxynucleotides sequence ZL combined with luciferase reporter plasmid was used. A breast cancer cell line SK-BR-3 was exposed to different conditions to investigate the effects of such factors as ZL concentration, PGM concentration, mechanical index (MI) and ultrasound exposure duration on transfection efficiency and cell viability. The transfection efficiency and cell viability by other lipid vectors such as lipofectamine and liposome were also tested, whose results were comparied with that of PGM. Transfection efficiency was detected by fluorescence microscopy. Cell viability was verified by PI (propidium iodide) assay. RESULTS: Among the factors tested, ultrasound exposure duration, MI and PGM concentration had obvious impacts on transfection efficiency and cell viability. The results showed that the optimal ultrasound condition was the exposure to ultrasound at MI 1.0 for 30 s with 2% PGM concentration, which gave an overall transfection efficiency of 78% +/- 10%, increased nearly 18 folds over the transfection by PGM (4.0%) or lipofectamine (4.3%) without ultrasound. Under same ultrasound conditions, different vectors showed significant difference in transfection efficiency while there are similar results in cell viability. CONCLUSION: Under proper ultrasound conditions, PGM can markedly enhance AS-ODNs transfection efficiency.

Breast Neoplasms↗
PubMed1998

Prediction of idiopathic respiratory distress syndrome by the stable microbubble test on gastric aspirate.

We evaluated the usefulness and accuracy of the stable microbubble test (SMT) performed on gastric aspirates of neonates to predict idiopathic respiratory distress syndrome (IRDS) and compared the results with those of the shake test, using the clinical characteristics of IRDS as the gold standard for the diagnosis of IRDS. One hundred forty paired samples of gastric aspirates, obtained within 1 hour of delivery from neonates with gestational ages between 27 and 42 weeks (mean, 36.6+/-3.5 weeks) and birth weights between 800 and 4,090 grams (mean 2,571+/-826 grams ) were evaluated. The sensitivity and specificity of the SMT with a predefined cut-off value of less than 20 bubbles/mm2 were 94.7% and 95%, respectively, with a positive and negative predictive value of 75% and 99.1%, respectively. The positive predictive value and specificity were increased to 100% in premature neonates. These values, especially the positive predictive value and specificity, were much higher than those obtained with the shake test. We conclude that the SMT on gastric aspirates obtained within 1 hour of delivery is a rapid and simple procedure to identify those neonates who will develop IRDS and who may benefit from prophylactic exogenous surfactant replacement.

Chi-Square Distribution↗
PubMed2002

Detection of air microbubbles in the internal jugular vein after intravenous injection of contrast agent for the diagnosis of patent foramen ovale.

The use of agitated air and saline, injected intravenously, combined with monitoring of the middle cerebral artery using transcranial Doppler sonography, is an effective method for detecting paradoxic cerebral embolism caused by right-to-left intracardiac shunting. This technique is particularly useful in patients with a patent foramen ovale. In patients without temporal acoustic windows, the method can be modified by using sonographic monitoring of the common carotid artery. Observation of saline-contrast microbubbles in the internal jugular vein during this procedure suggests incompetence of the ipsilateral internal jugular valve. This noninvasive method may thus be useful for studying the competence of the internal jugular valve.

Aged↗
PubMedDate not supplied

Characterization of focal liver lesions using contrast-enhanced sonography with a low mechanical index mode and a sulfur hexafluoride-filled microbubble contrast agent.

PURPOSE: To characterize focal liver lesions (FLLs) using real-time contrast-enhancedsonography (CEUS) with a low mechanical index mode and a sulfur hexafluoride-filled microbubble contrast agent. METHODS: CEUS was performed in 190 patients with FLLs, including hepatocellular carcinoma (HCC) (n = 107), liver metastasis (n = 21), intrahepatic cholangiocarcinoma (ICC) (n = 7), liver hemangioma (n = 37), focal nodular hyperplasia (FNH) (n = 11), regenerative nodule (n = 6) and liver lipoma (n = 1). The cadence contrast pulse sequencing technique and the contrast agent SonoVue(R) were used for CEUS examination. The enhancement patterns during the arterial, portal, and late phases were evaluated. RESULTS: HCC showed hyperenhancement in 100 (93.5%) of 107 nodules during the arterial phase and hypoenhancement in 102 (95.3%) during the late phase. Liver metastases showed homogeneous enhancement in 8 of 21 (38.1%) nodules and a peripheral regular rim-like enhancement in 11 of 21 (52.4%) nodules during the arterial phase and marked hypoenhancement in 16 of 21 (76.2%) nodules during the late phase. ICC exhibited irregular rim-like enhancement in 4 of 7 (57.1%) nodules during the arterial phase and hypo-enhancement in 7 of 7 (100%) nodules during the late phase. Hemangioma showed peripheral nodular hyperenhancement, and progressive centripetal enhancement was seen in 35 of 37 (94.6%) lesions during the arterial phase. All 11 cases of FNH exhibited homogeneous hyperenhancement during the arterial phase and hyperenhancement (n = 1) or isoenhancement (n = 9) during the late phase. The sensitivity, specificity, and positive predictive value, respectively, were 88.8%, 89.2%, and 91.3% for HCC; 81%, 100%, and 100% for liver metastasis; 57.1%, 100%, and 100% for ICC; 94.6%, 100%, and 100% for liver hemangioma; and 90.9%, 97.8%, and 71.4% for FNH. CONCLUSIONS: Low-mechanical index CEUS permits real-time, complete assessment of vascularity in FLLs, which in turn facilitates their characterization.

Adult↗
PubMed2002

Fetal gene transfer by intrauterine injection with microbubble-enhanced ultrasound.

Intrauterine injection of naked DNA expressing luciferase, green fluorescent protein (GFP), or beta-galactosidase (beta-gal) and fluorescein isothiocyanate-labeled oligodeoxynucleotide (FITC-ODN), in combination with microbubble-enhanced ultrasound (US), referred to as the "shotgun method" (SGM), produced high-level protein expression in fetal mice. With the SGM, luciferase expression increased approximately 10(3)-fold in comparison with expression after injection of naked DNA alone. Electron microscopic analysis demonstrated transient formation of pores on the skin surface after intraamniotic (i.a.) injection with the SGM. Widespread expression of GFP and beta-gal and delivery of FITC-ODN were observed in multiple fetal tissues adjacent to the injection points. PCR analysis indicated that germline transfection was only transient following intraperitoneal (i.p) injection, and there was no evidence of transfer of the reporter gene to the offspring. Thus, SGM might provide a useful means to clarify the molecular mechanisms of genetic diseases in utero, as well as a tool to develop gene therapies in utero.

Amnion↗
PubMedDate not supplied

Dynamic contrast-enhanced ultrasound with carbon dioxide microbubbles as adjunct to arteriography of liver tumors.

PURPOSE: The goal of the study is to evaluate utility of contrast-enhanced ultrasound (US) with carbon dioxide microbubbles in evaluation of hepatic lesions. METHODS: Twenty-eight patients with single or multiple hepatic lesions (11 hepatocellular carcinoma, 8 hemangiomas, 5 metastases, 1 adenoma, 1 focal nodular hyperplasia, 2 regenerative nodules) were examined. US exam was performed during intraarterial injection of 10 ml of CO2 through the same catheter employed for liver arteriography. The US exam was videotaped in its salient phases. Characteristics of enhancement were evaluated and correlated with histological findings or patient follow-up. RESULTS: Sonographic angiography clearly demonstrated vascularization of the lesions. Hepatocellular carcinoma, hemangioma, metastases, focal nodular hyperplasia, and regenerative nodules had very characteristic patterns. The injection of CO2 allowed detection of small additional nodules. CONCLUSION: Sonographic angiography can improve characterization and staging of hepatic tumors. Low cost and the simplicity of the technique should encourage further experimentation.

Angiography, Digital Subtraction↗
PubMed1995

Internalization of microbubbles by tumor cells in vivo and in vitro.

Lipid-coated microbubbles (LCM) administered intravenously (i.v.) to rats bearing brain tumor, specifically enhance tumor visualization by ultrasound [1]. In order to understand the basis for this observation, we have examined the interactions of LCM with glioblastoma (C6) and gliosarcoma (9L) tumor cells in vivo and in vitro. LCM and LCM labeled with the fluorescent lipophilic dye 3,3'-dioctadecyloxacarbocyanine perchlorate (diO) were administered to rats bearing brain tumor. LCM and diO-labeled LCM were found principally at the tumor site with no evidence of label in the surrounding normal brain tissue. Analysis of the tumor by confocal laser scanning microscopy revealed that labeled LCM were inside the tumor cells. Similar analysis of LCM interactions with C6 and 9L cells in culture showed that LCM first adsorb at the surface of the cells, and with time became localized inside the cells. Binding and internalization proceeded faster at 37 degrees C than at room temperature (RT). Staining of live cells with N-(3-((2,4-dinitrophenyl)amino)propyl)-N-(3-aminopropyl) methylamine dihydrochloride (DAMP), a dye that recognizes acidic compartments, showed that the majority of internalized LCM was associated with compartments containing DAMP. If the same uptake mechanism were operative in vivo, it would indicate that a portion of LCM bypasses the reticuloendothelial system and become endocytosed directly by tumor cells.

Animals↗
PubMed1993

Stable microbubble test for predicting the risk of respiratory distress syndrome: I. Comparisons with other predictors of fetal lung maturity in amniotic fluid.

With the advent of surfactant replacement therapy, there is an increasing need for a rapid test of predicting the development of respiratory distress syndrome (RDS). We evaluated the clinical usefulness of the stable microbubble (SM) test in predicting the development of RDS by comparison with other tests in amniotic fluid samples obtained within 12 h before delivery from 40 pregnancies between 23-35 weeks of gestation. These tests included the lecithin/sphingomyelin (L/S) ratio, disaturated phosphatidylcholine/sphingomyelin (DSPC/S) ratio, concentrations of lecithin, DSPC, and surfactant-associated proteins A and B, C (SP-A, SP-B,C). The cut-off value of each test for predicting RDS was determined at a point of maximum diagnostic accuracy. The overall diagnostic accuracy of the SM test was similar to that of other tests. However, both the SM test and the SP-B,C concentration had positive predictive values of 100%. We conclude that the rapid (< 10 min) and reliable information obtained by this test should encourage its use in defining a population of neonates with surfactant deficiency in a multicentre trial of prophylactic surfactant therapy.

Amniotic Fluid↗
PubMed1993

Stable microbubble test for predicting the risk of respiratory distress syndrome: II. Prospective evaluation of the test on amniotic fluid and gastric aspirate.

We determined prospectively if the stable microbubble (SM) test on gastric aspirate obtained at birth was as useful as that on amniotic fluid in predicting respiratory distress syndrome (RDS). One hundred and five paired samples of amniotic fluid obtained at delivery from 105 consecutive women with gestation of 35 weeks or less and gastric aspirates from their neonates obtained within 30 min of birth were studied. The SM test with the predefined cut-off value of less than 5 bubbles/mm2 for amniotic fluid and less than 10 bubbles/mm2 for gastric aspirate signified the risk of RDS with the positive predictive value of 100% and 96% and with the negative predictive value of 91% and 84%, respectively. We conclude that the SM test on both amniotic fluid and gastric aspirate obtained at birth is a rapid (< 10 min), simple and reliable procedure for predicting neonates who will develop RDS. It may be used as a bedside test to define a population of neonates with surfactant deficiency in clinical trials of prophylactic surfactant therapy.

Amniotic Fluid↗
PubMed2001

Microbubble potentiated ultrasound as a method of declotting thrombosed dialysis grafts: experimental study in dogs.

Intravenous perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles in the presence of low frequency ultrasound (LFUS) can lyse very small clots. We develop a similar method to declot full-size arteriovenous dialysis grafts. Dialysis grafts fashioned in three dogs were cannulated and ligated. After thrombosis, three declotting techniques were randomly applied: 1) direct injection of PESDA + LFUS; 2) direct injection of saline + LFUS; and 3) intravenous PESDA + LFUS. Declotting was graded by cine angiography scores of each third of the graft on a scale of 0-4 (maximum total score = 12). Twenty-six procedures showed mean patency scores of 11.1 for direct PESDA and 8.4 for i.v. PESDA, vs 4.9 for direct saline, p = <0.001. All eight direct PESDA injections achieved lysis and good flow, but none of 8 direct saline injections succeeded, p = <0.01. Intravenous PESDA succeeded in 4 of 10 procedures, p = <0.04 vs saline. Direct injection of PESDA with transcutaneous LFUS succeeds in lysing moderate-size clots and recanalizing thrombosed fistulas.

Animals↗
PubMed1997

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant.

UNLABELLED: Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. CONCLUSION: Surfactant therapy normalizes the surfactant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients.

Albumins↗
PubMed1988

Myocardial risk area and peak gray level measurement by contrast echocardiography: effect of microbubble size and concentration, injection rate, and coronary vasodilation.

Contrast agents were injected via the intracoronary route in eight dogs during two-dimensional echocardiographic imaging to determine the influence of microbubble size and concentration, injection rate, and coronary vasodilation on risk area and peak gray level measurement. At an injection rate at 13 cc/sec, the average background-subtracted peak gray level intensity of hand-agitated diatrizoate meglumine/diatrizoate sodium was significantly (p less than 0.01) higher than that of hand-agitated diatrizoate meglumine/diatrizoate sodium + 0.9% saline, sonicated diatrizoate meglumine/diatrizoate sodium, and sonicated 70% sorbitol. These differences were abolished by the use of 38 cc/sec injection rates and intracoronary injection of adenosine. Perfusion area determinations as assessed by planimetry were unaffected by the contrast agent used, the injection rate, or by intracoronary administration of adenosine. We conclude that risk area measurement by the ultrasound contrast technique is not affected by varying contrast agents, injection rates, or vasodilation. However, peak gray level intensity is variable among contrast agents and may result in variability of time-activity curve analysis.

Animals↗