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PubMed1998

Sonographic evaluation of focal nodular hyperplasias (FNH) of the liver with a transpulmonary galactose-based contrast agent (Levovist).

Focal nodular hyperplasias (FNH) are hypervascular, benign focal liver lesions. Differentiation of FNH from other focal liver lesions is of clinical importance. The purpose of this study was to examine the impact of a new, transpulmonary echo-enhancing agent SHU 508A (Levovist) and recent Doppler techniques in the sonographic evaluation of FNH. 43 patients with 61 focal nodular hyperplasias of the liver were examined with grey scale ultrasound and power Doppler ultrasound. Levovist, a galactose-air-microbubble suspension was administered intravenously in all patients, either by bolus injection (400 mg ml-1) or continuous pump-infusion (300 mg ml-1). Visualization of the feeding vessels and vascularity of the lesions were evaluated. The resistance indexes (RI) in the feeding vessel and the hepatic artery were assessed and compared with the diameters of the FNH. The mean diameter of FNH was 4.3 cm (+/- 1.0). Echo enhanced power Doppler ultrasound was superior to unenhanced power Doppler ultrasound in the detection of the feeding artery (85% vs. 98%) in FNH and depicted the internal vascular architecture more clearly, especially in lesions located in the left lobe of the liver. Lesions smaller than 3 cm did not show a characteristic vascular architecture with echo enhanced Doppler ultrasound. The resistance index of the feeding artery (mean: 0.51 +/- 0.08) is significantly (p < 0.0001) lower than that of the hepatic artery (mean 0.65 +/- 0.06) with a mean difference of -0.14 +/- 0.01 in the same patient. The RI of the feeding artery significantly decreased as the size of the FNH increased, whereas RI differences between the hepatic artery and the feeding artery increased with lesion size. Intravenous (i.v.) bolus injection of the contrast agent will depict the hypervascular nature of FNH more clearly than i.v. infusion, although the latter will significantly prolong the diagnostic window. In conclusion, i.v. infusion of Levovist improves the visualization of the feeding artery and the radiating vascular architecture in FNH located in the left lobe of the liver due to improved signal-to-noise ratio and results in more effective suppression of motion artefacts. Although echo enhanced Doppler ultrasound improves the detection of the low resistance arterial feeding vessel in small FNH, it will not, however, reveal a specific vascular pattern in these lesions.

Adult↗

PubMed2002

Hepatocellular adenoma: diagnostic difficulties and novel imaging techniques.

We report the case of a 30-year-old eastern European female who presented with right upper quadrant pain. Clinical examination was unremarkable and liver function tests were normal. CT identified a 5 cm lesion in segment V of the liver, which was of homogeneous low density with no calcification or significant enhancement. MRI showed the lesion to be hypointense to liver on T(1) weighted sequences and isointense on T(2) weighted sequences. Rapid arterial enhancement with gadolinium-DTPA faded without leaving a definite central scar. Ultrasound showed the lesion to be echogenic with minimal vascularity. Administration of a liver-specific microbubble contrast agent showed low uptake relative to the surrounding liver. Phosphorus-31 MR spectroscopy, localized to the lesion itself, revealed a markedly increased phosphomonoester resonance with a decreased phosphodiester resonance, compatible with increased cell turnover. Biopsy confirmed the lesion to be a hepatocellular adenoma. The diagnosis of a hepatic adenoma is difficult with tissue diagnosis the gold standard, but it may be suggested by a combination of imaging modalities. We have described two new imaging techniques not previously described in characterization of hepatic adenomata, namely ultrasound with contrast agent and MR spectroscopy.

Adenoma↗

PubMed2006

Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study.

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

Adult↗

PubMed2005

Fringe probing of gas-liquid interfacial film in a microcapillary tube.

An optical diagnostic technique has been developed to measure the gas-liquid interfacial film thickness in microcapillary two-phase flows. The spatial frequencies from the multiscattering measured with a CCD camera are used to determine the slug diameter and film thickness. It is found that, with an optimized optical orientation angle, the spatial frequency method shows great accuracy in the measurements. To demonstrate the capability of the newly developed method, a validation experiment was conducted in water-air and water-honey mixture-air two-phase flows. We measured the spatial frequency variations when the microbubble and slug were pulsating by utilizing a highly accurate signal processing technique and a five-point interpolation method. This newly developed optical method is easy to implement, and it will be a useful technique for two-phase flow measurements.

Journal Article↗

PubMed1992

Ultrasonographic approach to diagnosing hydropneumothorax.

Ultrasound results for 11 patients with HPN confirmed by CXR were compared with those for 100 healthy subjects. The observation of the hyperechogenic line of the pleuropulmonary surface (normal subjects) showed back-and-forth respiratory movements in every case which we call the "gliding sign." Ultrasonographic signs were shown in all patients with HPN. Visualizing the gassy effusion above the pleural fluid, the disappearance of the "gliding sign" (n = 11) indicates PN. The image of the HPN allows in addition a "curtain sign" which depicts the movement of air/fluid level (n = 11), the pulmonary collapse being calculated across the liquid window whose echostructure is analyzed. A "polymicrobullous" image (n = 2) caused by air microbubbles within the fluid effusion, is reported. We conclude that echography appears to be a new approach to diagnosing HPN, which is particularly useful during or after ultrasonically guided procedures including pleural drainage, and should be recognized by sonographers.

Adult↗

PubMed1994

Atrial-esophageal fistula shown by transthoracic echocardiogram.

Nontraumatic atrial-esophageal fistula is a catastrophic problem usually diagnosed postmortem and almost invariably fatal. We report the first case of a patient in whom the diagnosis of atrial-esophageal fistula was made from a transthoracic echocardiography antemortem. Echocardiography showed multiple microbubbles in the left atrium and ventricle emanating from the posterior aspect of the left atrium adjacent to the pulmonary veins. The literature is reviewed and the significance of the case and the echocardiogram is discussed.

Echocardiography↗

PubMed2006

Hemodynamic changes induced by recreational scuba diving.

OBJECTIVE: Cardiac changes induced by scuba diving were investigated using Doppler echocardiography. MATERIAL AND METHODS: Ten healthy scuba divers dove to a mean depth of 34.3 +/- 2.7 m of sea water (113 +/- 9 feet) and a mean duration of 25.3 +/- 3.5 min. RESULTS: One hour after the dive, microbubbles could be detected in the right-heart chambers of all subjects. Left atrial and left ventricular (LV) diameters significantly decreased after the dive. Cardiac output, assessed by aortic blood flow, remained unchanged. Heart rate increased and stroke volume (SV) decreased after the dive. LV filling was assessed on transmitral profile. An increase of the contribution of the atrial contraction to LV filling was observed. Right cavity diameters were unchanged, but an increase of the right ventricular/right atrial gradient pressure was found. CONCLUSION: The diving profile studied promotes a rather important bubble grade in all volunteers. A significantly reduced cardiac diameters and SV was found by our hemodynamic study 1 h after diving. Two factors can explain these results: low volemia secondary to immersion, and venous gas embolism induced by nitrogen desaturation. Consequently, restoration of the water balance of the body should be considered in the recovery process after diving.

Adult↗

PubMed1982

M-mode and two-dimensional echocardiography in congenital absence of the pericardium.

The M-mode and two-dimensional echocardiographic features of congenital absence of the pericardium are described in two cases that had been confirmed by clinical and radiological data. The M-mode echocardiogram showed right ventricular dilatation and abnormal systolic motion of the interventricular septum. Echo contrast studies with peripheral injection of saline solution revealed normal persistence of microbubbles in the right side of the heart. Two-dimensional short axis parasternal views showed some dilatation of the right ventricle, with anterior displacement of the left ventricular cavity in systole, which appeared to be wider than the posterior motion of the interventricular septum towards the posterior wall. The resulting positive motion of the interventricular septum toward the transducer could account for the abnormal pattern seen in the M-mode echocardiogram. Congenital absence of the left pericardium has particular echocardiographic features not diagnostic for the anomaly. However, the M-mode and two-dimensional echocardiographic studies, used in conjunction with the echocontrast techniques, seem to help in the differential diagnosis and for excluding associated anomalies.

Adult↗

PubMed2005

Intravenous alteplase for acute ischaemic stroke.

Thrombolysis with intravenous alteplase is the only validated and approved treatment for acute ischaemic stroke. It is currently licensed for use within 3 h of stroke onset. This treatment improves functional outcome without increasing mortality, although it can initially cause a devastating intracerebral haemorrhage. Risk factors for this complication have been identified and postmarketing studies have shown an acceptable safety profile when the guidelines for drug prescription and administration are rigorously applied. Intravenous alteplase is weakly effective in recanalising major intracranial artery occlusions and more potent strategies of reperfusion are needed. Ongoing clinical trials are evaluating alteplase combined with transcranial ultrasound and intravenous microbubbles, alteplase at reduced doses combined with intravenous glycoprotein IIb/IIIa inhibitors and intravenous alteplase at a reduced dose followed by intra-arterial recanalisation.

Brain Ischemia↗

PubMed2007

Strategies to achieve systemic delivery of therapeutic cells and microbes to tumors.

In order to more effectively treat cancer, targeted delivery of therapeutic agents will be needed. The creation of delivery vehicles capable of locating and entering tumors before delivering a therapeutic payload will, therefore, enable the design of more beneficial and less toxic treatment platforms. Although nanoparticles, microbubbles and liposomes may also partially address these issues, the use of biological agents as delivery vehicles presently holds much promise. Through the hijacking of natural pathogen or cell trafficking pathways it is possible to actively target such agents to the tumor; they are then capable of selective replication (multiplying their therapeutic potential) and may be directly cytolytic themselves and/or may be utilized to deliver therapeutic genes. These agents, such as oncolytic viruses, attenuated bacteria and eukaryotic cells (cellular immunotherapeutics and progenitor and stem cells) will be discussed along with the mechanisms employed to deliver them systemically to tumors, including disseminated disease and micrometsastases.

Animals↗

PubMed2003

Color Doppler sonography with contrast in the differentiation of ovarian tumors.

UNLABELLED: The objective of this study was to differentiate benign ovarian tumors from malignant ones before surgery using color and pulsed Doppler sonography, and to compare results obtained before and after use of contrast medium, thereby verifying whether contrast results in an improvement in the diagnostic sensitivity. METHODS: Sixty two women (mean age 49.9 years) with ovarian tumors were studied, 45 with benign and 17 with malignant tumors. All women underwent a transvaginal color Doppler ultrasonographic exam. A study of the arterial vascular flow was made in all tumor areas, as well as an impedance evaluation of arterial vascular flow using the resistance index. RESULT: Localization of the vessels in the tumor revealed a greater proportion of malignant tumors with detectable internal vascular flows (64%) than benign tumors with such flows (22%). There was a considerable overlap of these findings. The use of contrast identified a greater number of vessels with confirmation in the totality of tumors, but did not improve the Doppler capacity in tumoral differentiation. Malignant tumors presented lower values of resistance index than the benign ones, whether or not contrast was used. The cutoff value for resistance index that better maximized the Doppler sensitivity and specificity was 0.55. Through this value, an increase of the sensitivity after contrast use was obtained, varying from 47% to 82%, while specificity remained statistically unchanged. CONCLUSION: Although the injection of a microbubble agent improved the sensitivity of the method detecting vascularization of tumors, a positive finding for vascularization by this method was not clinically useful in the differentiation of benign and malignant ovarian tumors.

Adolescent↗

PubMed2004

Contrast echocardiography in the diagnosis of intrapulmonary vascular dilations in patients eligible for liver transplantation.

OBJECTIVE: To determine the importance of contrast echocardiography in the diagnosis of intrapulmonary vascular dilations (PVD) in patients with severe hepatic diseases, eligible for transplantation. METHODS: Transthoracic echocardiography (TTE) with second harmonic imaging was performed in 76 patients, among them 32 patients were consecutively undergone to a transesophageal study (ETE). Echocardiographic contrast was obtained from microbubbles derived from the injection of agitated saline solution, in venous peripheral access. Abnormal presence of contrast in the left cardiac chambers was considered positive, with a delay of 4 to 6 cardiac cycles, after initial opacification of the right cardiac chambers. RESULTS: PVD diagnosis was performed in 53.9% of the patients (41/76). Sensibility, specificity, positive predictive value, negative predictive value, and accuracy of the TTE in relation to the ETE was 75%, 100%, 100%, 80% and 87.5%, respectively. Echocardiography was positive in 37 (55.2%) of 67 nonhypoxemic patients, and in 4 (44.4%) hypoxemic ones. No cardiologic hemodynamic repercussions from intrapulmonary shunt were observed. CONCLUSION: The contrast echocardiography is efficient, easy to be used, and safe in the search for and identification of intrapulmonary vascular alterations in patients eligible for hepatic transplantation.

Adult↗

PubMed2006

Cavitation bioeffects.

Acoustic cavitation takes place when tiny gas bubbles oscillate, grow, and collapse in liquid under the influence of ultrasonic field. This study reviews cavitation bioeffects that are found both in vivo and in vitro when exposed to either low- or high-power acoustics. Proposed mechanisms are discussed here as well based on theoretical studies, simulations and test bench experiments. Bioeffects are induced in living tissue once the gas bubble is, for instance, within a blood vessel in close vicinity to the endothelium or to the red blood cells. Conditions for inducing various bioeffects are discussed - from severe damage, such as cell necrosis, to delicate alterations, such as increased permeability of cell membrane. Present and potential applications for therapeutic purpose from stone pulverization and tissue ablation to gene transfection and transdermal delivery are reviewed including the growing use of artificial microbubbles.

Acoustics↗

PubMed2006

Mechanism of porphyrin-induced sonodynamic effect: possible role of hyperthermia.

The biological effects of ultrasound have been investigated vigorously for various applications including the thermal coagulation of tissues, the opening of tight junctions, and localized gene or drug introduction. The synergistic cell killing effect of ultrasound and porphyrin derivatives, the so-called sonodynamic effect, holds promise for cancer treatment. Although several models to explain the sonodynamic effect have been proposed, its exact mechanism, especially in vivo, remains unknown. We examined the effect of a porphyrin derivative, protoporphyrin IX, on ultrasound-induced killing of HeLa cells. In some experiments, the intracellular protoporphyrin IX concentration was increased by 5-aminolevulinic acid treatment of the cells. Although extracellular protoporphyrin IX showed an enhanced cell killing effect by microbubble-enhanced ultrasound, intracellular protoporphyrin IX did not. On the other hand, intracellular protoporphyrin IX enhanced the cell killing effect of hyperthermia, which can be produced by ultrasound exposure, in a moderately acidic environment (pH 6.6). Because porphyrin derivatives are generally imported into the intracellular component in vivo, our results suggest that hyperthermia caused by ultrasound may play an important role in the sonodynamic effect induced by porphyrin derivatives.

Aminolevulinic Acid↗

PubMed2003

Hyperoxemic perfusion for treatment of reperfusion microvascular ischemia in patients with myocardial infarction.

In patients with acute myocardial infarction (AMI) primary angioplasty and stent placement is a more effective and better tolerated treatment than thrombolysis, and therefore, when logistics allow, this treatment is preferred and routinely used. However, successful reopening of an occluded coronary artery does not necessarily lead to recovery of left ventricular (LV) function. Post-AMI reduction in contractile function and ventricular remodeling may result in heart failure. There is evidence that reduced contractile function in the infarct zone is related to poor microvascular perfusion even after normalization of large-vessel flow by angiographic criteria following coronary recanalization. Failure to re-establish adequate tissue perfusion may be because of reperfusion injury, ischemia-induced microvascular damage, and plugging of the microcirculation by thrombus and plaque during mechanical recanalization. Experimental data support the hypothesis that reperfusion microvascular ischemia contributes to myocardial tissue injury over a prolonged time period. Hyperbaric oxygen therapy (HBO) attenuates microvascular dysfunction and reperfusion microvascular ischemia, as demonstrated in both experimental models and patients with AMI. However, treating patients in an HBO chamber or with a conventional oxygenator is impractical and difficult. Aqueous oxygen (AO) is a newly developed solution containing extremely high oxygen concentrations (1-3 ml O(2)/mL saline). The AO system mixes AO solution with a patient's blood from an arterial puncture and delivers the hyperoxemic blood to targeted ischemic myocardium via an infusion catheter for regional correction of hypoxemia and production of hyperoxemia. The system precisely controls the level of pO(2) without clinically significant microbubble formation. Hyperoxemic coronary infusion of AO in experimental models of AMI improved LV function and reduced infarct size compared with normoxemic controls,very likely as a result of microvascular blood flow improvement. The first clinical experiences with intracoronary infusion of AO solution demonstrated the therapy to be a safe and well tolerated in the setting of AMI after successful primary percutaneous transluminal coronary angioplasty. Its use was associated with significant progressive improvement in LV function as measured by ejection fraction and wall motion score index. Interestingly, such improvement was primarily due to functional recovery of infarct zone contractility. A larger randomized trial is currently underway to define the role of hyperoxemic coronary infusion in patients with AMI.

Animals↗

PubMed2004

Disintegrins.

The existence of disintegrins, non-enzymatic, small molecular weight proteins from viper venom, has been known for 2 decades, and their impact on cellular research has been substantial and far-reaching. Disintegrins have been the molecular scaffold used in the design of therapeutics for the prevention of thrombosis and cancer. Their sequencing has provided insights into the evolution of proteins over millennia. Production of recombinant disintegrin mutants and fusion proteins has allowed investigations into molecular mechanisms at work in cell-extracellular matrix interactions. Structural homologies with non-snake proteins have shown disintegrin-like molecules in species ranging from slime mold to humans. Intracellular signaling events have been elucidated through the use of venom disintegrins, including events related to programmed cell death, motility, cell proliferation and viral pathogenesis. Disintegrin sequences (protein or genes) have been placed in microbubbles and liposomes and been found to target neovascular endothelium and metastatic tumors in two mouse models. The purpose of this review is to highlight the members of this disintegrin family discovered since 1998 as well as the increased understanding of their usefulness in therapeutics and technical assays.

Amino Acid Sequence↗

PubMed1978

Ultrasonographic appearance of gas-containing abscesses in the abdomen.

This report describes the sonographic appearance of six gas-containing abdominal abscesses. Gas-containing abscesses may appear as densely echogenic masses with acoustical shadowing, but may also be seen merely as regions of acoustical shadowing or as an echogenic mass. A hypothesis is advanced that the appearance of gas-containing abscesses as echogenic masses may be due to a "microbubble" constrast effect.

Abdomen↗

PubMed1982

Real-time sonographic detection of vesicoureteral reflux in children.

Real-time sonography and the principle of contrast sonography were used for evaluation of vesicoureteral reflux in children. Fifty-five kidneys were examined during the filling phase of cystourethrography. Of 15 positive cystograms, with grade II or greater reflux, 13 sonograms were positive. A positive sonogram was defined as visualization of moving microbubbles within the renal collecting system and/or dilatation of the collecting system during the course of bladder filling. This method may prove to be of value in the management of children with vesicoureteral reflux, particularly because sonography provides good visualization of renal size and parenchymal scarring while simultaneously demonstrating reflux.

Child↗