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PubMed1997

New developments in ultrasound systems for contrast echocardiography.

Contrast echocardiography (CE) has evolved significantly in the past decade. Contrast agents and the hardware and software used to detect them and display optimal images have developed in tandem. Not only are hardware and contrast agents available that allow left ventricular cavity enhancement, but recent research points to the usefulness of CE for the evaluation of myocardial perfusion in the cardiac catheterization laboratory and operating room. Advances in ultrasound technology, such as transient harmonic imaging and integrated backscatter, coupled with the development of newer contrast agents that contain smaller, more stable microbubbles capable of transpulmonary passage for intravenous injection, promise a vast increase in the applications of CE in clinical practice.

Contrast Media↗

PubMed2006

Clinical utility of contrast-enhanced echocardiography.

Over the past three decades, echocardiography has become a major diagnostic tool in the arsenal of clinical cardiology for real-time imaging of cardiac dynamics. More and more, cardiologists' decisions are based on images created from ultrasound wave reflections. From the time ultrasound imaging technology provided the first insight into a human heart, our diagnostic capabilities have increased exponentially as a result of our growing knowledge and developing technologies. One of the most intriguing developments that brought about a decade-long combination of expectations and disappointments was the introduction of echocardiographic contrast agents. Despite repeated waves of controversy regarding the readiness of this technology for clinical use, it has overcome multiple hurdles and currently provides useful clinical information that helps cardiologists to diagnose heart disease accurately. Since the initial reports on the use of ultrasound contrast media such as agitated saline or renografin, the major advances in the field of contrast echocardiography have included (1) the development of stable perfluorocarbon-filled microbubbles, frequently referred to as second-generation contrast agents; and (2) the development of contrast-targeted nonlinear imaging modes, such as harmonic imaging, pulse inversion, and power modulation, which allow consistent real-time visualization of these agents. These contrast agents in conjunction with the new imaging technology constitute powerful tools that improve our ability to evaluate left ventricular function and myocardial perfusion, and allow differential diagnosis of thrombi and intravascular masses. In this manuscript, we briefly review some of the literature that has provided the scientific basis for the use of echocardiographic contrast agents in the context of these important variables.

Contrast Media↗

PubMed1995

Preliminary effects of in vitro lipid exposure on absorbable poly(ortho ester) films.

Bioabsorbable films show promise in preventing postoperative interfacial tissue adhesion. Absorbable polymers in film form are generally more sensitive to chemical environments, due to their large surface area to volume ratio. The in vivo environment contains lipids such as cholesterol, triglycerides, and phospholipids, which are known to affect the degradation of permanent and absorbable polymeric biomaterials. Preliminary investigations of in vitro lipid exposure of bioabsorbable poly(ortho ester) (POE) films for implant use are described. POE has been studied previously for use in controlled drug delivery and fracture fixation. Six-week in vitro exposure of 65:35 POE films to a cholesterol emulsion (1 g/L) showed no apparent difference in hydrolytic degradation rates of mechanical properties or mass loss compared to deionized water exposed films. Decreases of 28 and 6% in inherent viscosity were observed after 5 weeks for cholesterol and deionized water exposed films, respectively, suggesting cholesterol may have some effect. Further examination of the data, due to sample variation, revealed that clear, uniform films showed only minor changes in mass loss and mechanical properties after 6 weeks in either of the in vitro media. But slightly cloudy films possessing microscopic bubbles showed accelerated degradation in both media, indicating the effect of cholesterol was inconclusive due to sample variation. Control of the microbubble formation process could have utility in controlling hydrolytic degradation of POE films.

Biocompatible Materials↗

PubMed1991

Improved biocompatibility of silicone rubber by removal of surface entrapped air nuclei.

Biomaterials activate the complement system which is important since C3a promotes platelet aggregation and release, and C5a activates neutrophils that may augment coagulation. Tiny air nuclei (microbubbles) are found in the surface roughness of biomaterials on exposure to a liquid, therefore two interfaces exist: (a) a blood/biomaterial, and (b) a blood/air interface. Experiments were carried out that documented that air bubbles activate complement and augment in vitro platelet aggregation in human plasma. The air nuclei were removed from the surface of silicone rubber by a technique termed denucleation to determine if complement activation and platelet aggregation could be reduced. We observed a significant reduction in C3a and C5a in the plasma samples incubated with denucleated silicone rubber as compared to the control samples (p less than 0.001, ANOVA). The plasma incubated with the denucleated silicone caused reduced platelet aggregation as compared to the plasma incubated with the control silicone when added to a platelet suspension (p less than 0.001, ANOVA). Surface chemical analysis by x-ray photo-electron spectroscopy (XPS) showed no change in the silicone rubber surface after the denucleation procedure.

Air↗

PubMed2004

Pitfalls in the detection of lipid vectors in neural cell culture and in brain tissue.

Lipid particles (liposomes and lipid-coated microbubbles) are currently studied as vectors for drug delivery to the central nervous system. The visualization of these particles is usually based on their labeling with a lipophilic fluorescent dye (3,3'-dioctadecycloxacarbocyanine perchlorate) or staining with Oil Red O. The purpose of this article was to highlight the difficulties and pitfalls encountered with the use of these techniques in the detection of lipid particles in neural cell cultures and in brain tissue. In vitro and in vivo studies were conducted on different neural cell cultures (rat and human tumors, microglial cells) and animal models of brain lesion (lipopolysaccharide and quinolinic acid-induced lesion, induced brain tumor). The cells or brain slices were observed with optical microscopy after staining with Oil Red O, fluorescent microscopy, or scanning electron microscopy. Intra and extracytoplasmic lipid particles (stained with Oil Red O or autofluorescent or visualized by scanning electron microscopy) were naturally found in the cells and tissues studied. Intracytoplasmic lipid microparticles were present in tumoral and microglial cells. These lipid microparticles were also observed with some extracytoplasmic lipid droplets in the induced brain lesions. These images could be misinterpreted as lipid vectors if the cells or animals would have been treated with such a vector.

Animals↗

PubMed2001

Contrast-enhanced color Doppler sonography of uveal melanomas.

PURPOSE: The purpose of our study was to evaluate the use of the galactose microbubble-based contrast agent Levovist in color Doppler sonography of uveal melanomas. We also evaluated the use of the resistance index and pulsatility index in differentiating tumor-associated vessels from normal vessels in patients with uveal melanomas. METHODS: In this prospective study, 40 patients with uveal melanoma were examined with color Doppler sonography before and after the administration of the contrast agent Levovist. The Doppler signals were recorded from both the tumor and the orbit and were evaluated quantitatively and qualitatively. RESULTS: Tumor-associated vessels were detected without contrast enhancement in 36 of 40 patients and with contrast enhancement in 38 of 40 patients. The spectral characteristics of the Doppler signals did not change after the injection of Levovist. There were no differences-qualitative or quantitative-in Doppler signals between normal and tumor-associated vessels. CONCLUSIONS: The injection of Levovist slightly improved the detection of small vessels in uveal melanomas and the orbit but did not help to differentiate between normal vessels and tumoral vessels. The differentiation of a solid tumor from subretinal hemorrhage or effusion was improved.

Adult↗

PubMedDate not supplied

Flash-echo gray-scale imaging in the subtraction mode for assessing perfusion of small hepatocellular carcinoma.

PURPOSE: The aim of this study was to evaluate the effectiveness of using flash-echo imaging (FEI) in the subtraction mode to assess the vascularity of small hepatocellular carcinomas (HCCs) that had been unsatisfactorily assessed with power Doppler sonography. METHODS: Between May 2000 and April 2001, we prospectively assessed nodular small HCCs using FEI in the subtraction mode after power Doppler sonography resulted in unsatisfactory images. After microbubble contrast was injected, we used the FEI technique to assess tumor perfusion in the arterial, portal, and delayed phases. RESULTS: Our study population comprised 14 patients (10 men and 4 women) whose ages ranged from 31 to 79 years (mean, 61 +/- 13.7 years) and whose tumors ranged in size from 0.8 to 3 cm (mean, 1.8 +/- 0.5 cm). Power Doppler sonography was unable to assess tumor vascularity in 6 cases because of interference by heart pulsation, and it failed to detect a color signal in the other 8 cases. All tumors were enhanced with FEI. In the arterial phase, 7 of the 14 tumors (50%) showed hyperperfusion relative to liver parenchyma enhancement, 5 of 14 (36%) showed isoperfusion, and 2 of 14 (14%) showed hypoperfusion. In the portal phase, 3 of the 14 tumors (21%) showed isoperfusion, and the other 11 (79%) showed hypoperfusion. In the delayed phase, all 14 tumors showed hypoperfusion. CONCLUSIONS: Despite heart pulsation and slow vascular flow, FEI in the subtraction mode was sensitive and effective in assessing the perfusion of small HCCs.

Adult↗

PubMed2004

Splenic hamartoma: presentation on contrast-enhanced sonography.

Splenic hamartoma is a rare benign tumor of the spleen. It is usually found incidentally at autopsy or splenectomy. We report a case of splenic hamartoma that was discovered during medical workup for vague upper abdominal pain. Abdominal sonography demonstrated a well-demarcated, slightly hypoechoic splenic solid mass; the mass was markedly enhanced on color Doppler sonography after injection of microbubble contrast agent. This finding may help to distinguish splenic hamartomas from other relatively common splenic tumors, such as hemangiomas or metastases.

Contrast Media↗

PubMed2006

Contrast-enhanced sonographic findings in a case of hepatobiliary cystadenoma with intracystic bleeding.

Intracystic slow bleeding is very difficult to diagnose using conventional sonography; consequently, a new sonographic technique has been sought. We present a histologically proven hepatobiliary cystadenoma with intracystic bleeding in which contrast-enhanced sonography (CEUS) showed microbubbles oozing from the cyst wall into the cystic cavity 10 minutes after intravenous injection of contrast medium. CEUS is an important diagnostic tool for diagnosing liver tumors, but the CEUS finding of slow intracystic bleeding has not been reported. Our observation suggests that this technique may be a new diagnostic tool for this purpose.

Contrast Media↗

PubMed2002

Targeted imaging using ultrasound.

The discipline of medical imaging is expanding to include both traditional anatomic modalities and new techniques for the functional assessment of the presence and extent of disease. Current FDA-approved ultrasound contrast agents are micron-sized bubbles with a stabilizing shell. Microbubble contrast agents can be used to estimate microvascular flow rate in a manner similar to dynamic contrast-enhanced magnetic resonance imaging (MRI). The concentration of these agents within the vasculature, reticulo-endothelial, or lymphatic systems produces an effective passive targeting of these areas. Liquid-filled nanoparticles and liposomes have also demonstrated echogenicity and are under evaluation as ultrasound contrast agents. Actively targeted ultrasound relies on specially designed contrast agents to localize the targeted molecular signature or physiologic system. These agents typically remain within the vascular space, and therefore possible targets include molecular markers on thrombus, endothelial cells, and leukocytes. The purpose of this review is to summarize the requirements, challenges, current progress, and future directions of targeted imaging with ultrasound.

Animals↗

PubMed1987

Microsecond-long flash photography of laser-induced ablation of biliary and urinary calculi.

High-speed flash photographs of laser-induced fragmentation of biliary and renal calculi under water were obtained using one-microsecond-long dye-laser pulses for both illumination and ablation. The photographs show the presence of a bubble with irregularities on the surface that suggest the early presence of debris or microbubbles. Fragmentation occurs before the bubble collapses, suggesting that fragmentation is due to laser-induced acoustic transients rather than to collapse of a laser-induced cavitation bubble.

Cholelithiasis↗

PubMed2005

Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy.

BACKGROUND AND OBJECTIVE: We developed a new approach that enhances selective photothermolysis of tumor through laser activation of synergistic phenomena around nanoclusters, which are self-assembled into cancer cells. STUDY DESIGN/MATERIALS AND METHODS: In vitro verification of this approach was performed by laser pulse irradiation (420-570 nm and 1064 nm; 8-12 nanosecond; 0.1-10 J/cm2) of MDA-MB-231 breast cancer cells targeted with primary antibodies to which 40-nm gold nanoparticles were selectively attached by means of secondary antibodies. Photothermal (PT) radiometry, thermolens techniques, electron microscopy, atomic force microscopy, silver and gold enhancing kits, and viability test (Annexin V-propidium iodide) were employed to study nanoparticle spatial organization, the dynamics of microbubble formation, and cell damage. RESULTS: The assembly of gold nanoclusters on the cell membrane was accompanied by increased local absorption and red-shifting as compared to cells that did not have nanoclusters. These effects were amplified by a silver-enhancing kit and pre-irradiation of cells with low laser-pulse energy. Finally, a significant increase in laser-induced bubble formation and cancer cell killing was observed using near-IR lasers (1064 nm). A cancer cell antigens was used to provide target specificity for nanoclusters formation making the cancer cells sensitive to laser activation. CONCLUSION: The described approach uses relatively small and simple gold nanoparticles offering more effective delivery to target. In addition, the further self-assembling of these nanoparticles into nanoclusters on live cells provides significant enhancement of laser-induced cell damage. These nanoclusters (gold "nanobombs") can be activated in cancer cells only by confining near-IR laser pulse energy within the critical mass of the nanoparticles in the nanoclusters.

Adenocarcinoma↗

PubMed2005

Utility of ultrasound stimulation for activation of pig oocytes matured in vitro.

The present study was carried out to examine the development of pig oocytes after exposing to ultrasound under various conditions. When oocytes were exposed to ultrasound in the sorbitol medium, the blastocyst formation rate was significantly (P < 0.01) higher than that of oocytes exposed in HEPES-TLP-PVA. Optison, an echo-contrast microbubble, prevented the development into blastocysts of oocytes exposed to ultrasound in the sorbitol medium (P < 0.01). The mean number of cells in the blastocysts developed from oocytes exposed to ultrasound with 10% duty cycle was significantly (P < 0.05) higher than that obtained by using ultrasound with 50% duty cycle. The blastocyst formation rate of oocytes exposed to ultrasound for 30 sec was significantly (P < 0.05) higher than that exposed for 10 sec. There were no significant differences in the rates of oocytes developed to the blastocyst stage and the mean numbers of cells in the blastocysts among different intensities of ultrasound. The pronuclear formation and second polar body extrusion rates of oocytes exposed to ultrasound did not differ from eclectically activated oocytes. Although there was no significant difference in the blastocyst formation rates between different activation methods, the mean number of cells in the blastocysts developed from oocytes activated by exposing to ultrasound was significantly (P < 0.05) higher than that obtained by applying electric pulses. The results of the present study showed that ultrasound stimulation can induce the nuclear activation and parthenogenetic development of pig oocytes matured in vitro.

Albumins↗

PubMed1993

Development and standardization of levothyroxine analysis by high-performance capillary electrophoresis.

This study demonstrates the development of a stability indicating capillary electrophoretic assay of levothyroxine. The optimum separation environment of the assay was determined by examining the effect of pH, buffer concentration, and sample additives on the levothyroxine peak resolution. Phosphate buffer (100 mM), pH 2.5, in a 27-cm capillary produced a satisfactory levothyroxine peak at approximately 10 min. An increase in the concentration of separation buffer increased the migration time and peak area of the levothyroxine peak. The peak symmetry was improved with the addition of methanol and acetonitrile in the sample matrix. However, acetonitrile and methanol concentrations above 25% produced current leakage, probably caused by the formation of microbubbles within the capillary. Standard plot of levothyroxine was established in the range of 3.75 to 60.00 micrograms/ml; with a sample size of 20 nl, this corresponds to 75-2000 micrograms of levothyroxine detected per run. Intra- and interday variability remained < 5% for the standard samples. Separation of levothyroxine from its possible deiodinated degradation products, triiodo- and diiodothyronine T3 and T2, was also obtained under these operating conditions.

Buffers↗

PubMed1996

Surface Tension of Aqueous Solutions of Electrolytes: Relationship with Ion Hydration, Oxygen Solubility, and Bubble Coalescence

The surface tension of aqueous solutions of simple inorganic electrolytes (36 in total) have been measured by the maximum bubble pressure method as a function of electrolyte concentration up to 1 M. In most cases the surface tension increased, however in a minority of cases, certain combinations of cations and anions had a negligible effect or decreased surface tension. Results were analysed in terms of surface tension/electrolyte concentration gradients (d(Deltagamma)/dc) and this parameter was found to correlate with the entropies of ion hydration, Jones-Dole viscosity coefficients and dissolved oxygen gradients. Calculation of Gibbs surface deficiencies for selected electrolytes were carried out using the raw surface tension data. Discussion of the surface tension/electrolyte concentration gradients was extended to the mechanism of inhibition of bubble coalescence by electrolytes. The Gibbs-Marangoni effect did not provide a satisfactory explanation for the inhibition of coalescence for all electrolytes and from the present study we suggest that dissolved gas (microbubble) gradients between macroscopic bubbles plays an important role in the coalescence process.

Journal Article↗

PubMed2000

Electrohydrodynamic Velocity and Pumping Measurements in Water and Alcohols.

Bubble and particle velocities in water and alcohols, under the influence of an electric field, were investigated in this work. Air bubbles were injected into the liquids through an electrified metal capillary insulated by glass with its tip left exposed. The end of the capillary from which the bubbles were released was conical in shape. Due to an electric field formed between the noninsulated capillary tip and a ground electrode immersed in the solvent, small bubbles were formed and used as tracers for the electrohydrodynamic (EHD) flow field. The pressure inside the capillary was measured for all liquids used in this study. For water, ethanol, and n-propanol, it was found that, at relatively low applied voltage, the pressure increases with voltage, reaches a maximum (pressure breakpoint), and then sharply decreases. This behavior is a result of the competition between the electric force appearing at the interface and the force due to the EHD flow near the capillary tip. The electric force tends to increase the pressure inside the capillary, while the EHD flow tends to decrease this pressure. For isopropanol and butanol, the pressure breakpoint was not observed in the range of voltage applied in the experiments. The EHD flow velocity was measured by using microbubbles and particles as flow tracers. An adaptive phase-Doppler velocimeter was employed to measure the velocity of bubbles, while the velocity of particles was measured by trajectory visualization of fluorescent particles. A discrepancy was observed between the two methods because of the location at which the measurements were made. It was found that average velocities of both bubbles and particles increase linearly with applied voltage. Experiments were also conducted to investigate pumping of water, which is a result of the EHD velocity near the capillary tip. The pumping flow rate was linearly related to the applied voltage and agreed well with EHD velocity measurements obtained from particle trajectories. Copyright 2000 Academic Press.

Journal Article↗

PubMed2005

Intravascular ultrasound-based imaging of vasa vasorum for the detection of vulnerable atherosclerotic plaque.

Vulnerable plaques are dangerous atherosclerotic lesions that bear a high risk of complications that can lead to heart attacks and strokes. These plaques are known to be chronically inflamed. The vasa vasorum (VV) are microvessels that nourish vessel walls. Proliferation of VV is part of the "response to injury" phenomenon in the process of plaque formation. Recent evidence has shown strong correlations between neovessel formation and macrophage infiltration in atherosclerotic plaque, suggesting VV density as a surrogate marker of plaque inflammation and vulnerability. We have developed a novel method for imaging and analyzing the density and perfusion of VV in human coronary atherosclerotic plaques using intravascular ultrasound (IVUS). Images are taken during the injection of a microbubble contrast agent and the spatiotemporal changes of the IVUS signal are monitored using enhancement-detection techniques. We present analyses of in vivo human coronary cases that, for the first time, demonstrate the feasibility of IVUS imaging of VV.

Coronary Artery Disease↗

PubMed1996

The value of colour Doppler imaging in assessing flow through ventriculo-peritoneal shunts.

So far, Doppler ultrasonography has had little application in paediatric neurosurgery. The incidental observation of normally invisible CSF flow from the peritoneal end of a ventriculo-peritoneal (V-P) shunt on colour Doppler during a conventional abdominal ultrasound examination in one of our patients suggested that colour Doppler imaging might be of potential interest. Using a 10-5 MHz broad-band linear array transducer, conventional 2D and Doppler (spectral and colour-coded) ultrasonography was performed in 17 patients with V-P shunts, who were aged 3 months to 12 years. In all, 20 examinations were performed, because 2 patients had repeat examinations before and after shunt revision. In 13 examinations (65%) CSF flow was identified through the shunt tube. Flow velocities between 5 and 7 cm/s were measured. No flow was seen in 7 examinations (35%), 3 of which (15%) were performed before revisions for a blocked shunt. Further in vitro studies with simulated shunt/ventricular system model demonstrated that although clear CSF is not ultrasonically visible, the presence of particulate matter, such as choroid plexus debris, can generate a satisfactory Doppler signal with the probe insonating over the length of the tubing. In the presence of clear CSF, turbulence generated at junction points of the shunt system or at the exit of the peritoneal tube can be visualised well with Doppler ultrasonography, presumably due to generation of microbubbles. The clinical implications for the management of shunt obstruction are discussed.

Cerebrospinal Fluid↗