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PubMedDate not supplied

Harmonic imaging with Levovist.

Our purpose was to test the hypothesis that second harmonic imaging preferentially detects backscatter from microbubbles compared with tissue structural components. A prototype second harmonic scanner was used to image a flow channel in a tissue-mimicking rubber phantom (liver density). Video time-intensity curves were calculated from repeated bolus injections of microbubble echocardiographic contrast material under the same fluid dynamic conditions but with three different imaging modes: (1) fundamental imaging at 2.5 MHz (transmit and receive at 2.5 MHz), (2) fun damental imaging at 5.0 MHz (transmit and receive at 5.0 MHz), and (3) second harmonic imaging (transmit at 2.5 MHz and receive at 5.0 MHz). Each video time-intensity curve was calibrated-such that quantitative backscatter intensity was measured relative to the tissue phantom (0 dB). The peak increase in backscatter from the contrast material in the channel relative to the tissue phantom and the intensity in the channel before the contrast effect (the noise floor) was measured along with the area under the calibrated time-intensity curve relative to the phantom. When referenced to the noise floor in the flow channel, all imaging modes produced approximately 25 dB of enhancement. However, when referenced to the tissue phantom, second harmonic imaging produced a 22.3 +/- 1.8 dB peak enhancement, which was greater than either fundamental imaging at 2.5 MHz (15.5 +/- 0.8 dB; p < 0.001) or fundamental imaging at 5.0 MHz (15.3 +/- 1.5 dB; p < 0.001). The area under the time-intensity curves confirmed that harmonic imaging has approximately 7 dB of relative enhancement to the phantom compared with fundamental imaging at either frequency. Second harmonic imaging specifically enhances backscatter from microbubbles compared with a tissue-mimicking phantom. This specificity for microbubbles is due to a decrease in backscatter for the tissue phantom, rather than an increase in backscatter for the microbubbles. These data support the hypothesis that second harmonic imaging may be able to detect microbubbles in the tissue vascular space by preferentially decreasing the backscatter from tissue structural components.

Echocardiography↗

PubMed2001

Gene delivery using ultrasound contrast agents.

With the human genome product and continuing advances in molecular biology many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Using physical properties of microbubbles and coating materials, genetic drugs have been incorporated into ultrasound contrast agents. Gene-bearing microbubbles can be injected IV and ultrasound energy applied to the target region. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing DNA. Cavitation also likely causes a local shockwave that improves cellular uptake of DNA. With transthoracic ultrasound, using commercially available diagnostic ultrasound system and an IV injection of gene-bearing microbubbles, high levels of transgene expression are observed in the insonated region of the myocardium. This new technology using microbubbles and ultrasound for gene delivery merits further study and development.

Animals↗

PubMed2002

Assessment of myocardial blood flow and volume using myocardial contrast echocardiography.

The development of new microbubble agents and ultrasound imaging modalities now allows the assessment of myocardial perfusion with echocardiography. Microbubbles also can be administered intravenously as constant infusions, which allows their concentration in blood to reach steady state. If the relation between microbubble concentration and video intensity is within the linear range, then myocardial video intensity will reflect the concentration of microbubbles in that region, which at steady state is the myocardial blood volume. The ability to destroy microbubbles and measure their replenishment into the ultrasound beam provides an opportunity to evaluate microbubble (or red blood cell) velocity. The product of myocardial blood volume and red blood cell velocity represents myocardial blood flow.

Blood Flow Velocity↗

PubMed1997

Ultrasound-mediated destruction of contrast agents. Effect of ultrasound intensity, exposure, and frequency.

RATIONALE AND OBJECTIVES: Although ultrasound contrast microbubbles theoretically could serve as tracers for the noninvasive quantification of blood flow, results have been inconsistent. Accurate quantification may be limited by ultrasound energy-mediated microbubble destruction. This study examined the effect of different ultrasound delivery parameters on microbubble destruction. METHODS: Experiments were performed in an in vitro hydraulic perfusion model consisting of a thin-walled rubber tube encased in agar. Ultrasonic parameters tested during different parts of the experiment were (1) intensity, (2) duration, and (3) frequency. Four ultrasound contrast agents: Aerosomes MRX115 (ImaRx Pharmaceuticals Corp., Tucson, AZ), Imagent AF0150 US (Alliance Pharmaceutical Corp., San Diego, CA), Levovist (Berlex Laboratories, Wayne, NJ), and Echogen (Sonus Pharmaceuticals, Bothel, WA) were imaged with three different ultrasound systems: ATL Ultramark AM-9 HDI, Vingmed 800 and Hewlett-Packard 2500. RESULTS: Microbubble destruction and reductions in reflectivity were noted in all agents tested. Although no significant reductions in counts or reflectivity occurred at 0.3 W/cm2 with any agent, exposure to 25 W/cm2 produced more than 80% reductions in both microbubble counts (P < 0.0001) and reflectivity (P < 0.0001). Declines in reflectivity were increased by longer exposure to ultrasound (P < 0.0001); slower flow through an ultrasound beam (P < 0.0001); continuous, rather than intermittent, imaging (P = 0.0002); use of a higher pulse repetition rate (P < 0.0001); and exposure to 2.5 MHz, rather than 7.5 MHz, ultrasound (P < 0.0001). CONCLUSIONS: Ultrasound energy-mediated destruction of contrast microbubbles is a function of many factors, including ultrasound intensity, duration, and frequency. Optimization of ultrasound delivery parameters may be used to maximize or minimize the destruction of ultrasound contrast agents.

Contrast Media↗

PubMed2002

Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium.

The early stages of atherosclerosis are characterized by increased endothelial cell (EC) surface expression of leukocyte adhesion molecules (LAMs). Ultrasound detection of acoustically active LAM-targeted microbubbles might provide a means to noninvasively assess the functional status of the endothelium. Toward this end, a lipid-based perfluorobutane-filled microbubble was synthesized with various densities of anti-ICAM-1 monoclonal antibodies conjugated to the bubble shell. We hypothesized that modulating the surface antibody density would permit regulation of the adhesion characteristics of the microbubbles, and that microbubble adhesion would be dependent on local wall shear rate. Coverslips of cultured human coronary artery ECs were exposed to microbubbles with various surface antibody densities (1%, 5%, 10%, 50%, 75%, and 100% of maximum coverage) at various wall shear rates (100, 175, 250, 350, and 500 s-1) in a parallel plate perfusion chamber. ECs were either normal or activated by interleukin-1 beta to overexpress ICAM-1. Adhesion was greater to activated vs. normal ECs (p < 0.001), increased with increasing surface antibody density (p < 0.01), and decreased with increasing wall shear rate (p = 0.02). We conclude that shell antibody density and wall shear rate are critical parameters controlling differential microbubble adhesion. This phenomenon might ultimately permit imaging of clinically relevant LAM expression in vivo.

Animals↗

PubMed2003

Blood flow quantification with contrast-enhanced US: "entrance in the section" phenomenon--phantom and rabbit study.

PURPOSE: To investigate changes in destruction-replenishment curves (in vitro and in vivo) that result from microbubble destruction in feeding vessels that pass through the imaging plane before microbubbles enter the region of interest (ROI). MATERIALS AND METHODS: During continuous injections of an ultrasonographic contrast agent, nonlinear gray-scale images were obtained in vitro in the longitudinal plane of a renal dialysis cartridge flow phantom (flow rates of 100, 200, and 400 mL/min) and in vivo in the coronal plane of the left kidneys of two rabbits (two kidneys). Destruction-replenishment curves were obtained for the dialysis cartridge in ROIs located immediately after the entrance of the microbubbles into the image plane and further from the entrance, after microbubbles had traveled across the complete length of the imaging plane. Replenishment curves were also obtained from ROIs in the rabbit kidneys at the level of segmental arteries, distal interlobar arteries, and the cortex. RESULTS: The ROIs immediately after the entrance of the microbubbles in the image plane of the dialysis cartridge and in the segmental artery of the kidney followed a typical exponential function, A(1 - e-alphat). Early portions of curves obtained in ROIs filled with microbubbles that had already passed through the image plane of the dialysis cartridge or in the renal cortex were not well described by such a function. The shape of the curve and the variations as a function of flow rate can be explained by means of a mathematical model based on indicator-dilution theory. CONCLUSION: When the feeding vessels of an ROI travel across the ultrasound field before they reach the measurement region, the typical shape of the replenishment curve is modified (reduced velocity parameter and plateau).

Animals↗

PubMed1992

Successful and reproducible myocardial opacification during two-dimensional echocardiography from right heart injection of contrast.

BACKGROUND: Myocardial contrast echocardiography currently involves intro-arterial injection of contrast. For this technique to have a broader application, it is necessary that myocardial opacification be achieved from a venous injection of contrast. METHODS AND RESULTS: To achieve myocardial opacification after right-side injection of contrast, two groups of open-chest anesthetized dogs were studied. Group 1 included nine dogs in whom microbubbles of various sizes, concentrations, and volumes were injected into the left atrium to determine microbubble characteristics that influence myocardial opacification. Group 2 included eight dogs in whom the effect of the combination of microbubble characteristics and myocardial blood flow on myocardial opacification was evaluated after right atrial injection of contrast. Background-subtracted time-intensity plots were generated from the myocardium to measure peak videointensity. In the group 2 dogs, digital subtraction and color coding were used to further highlight the contrast effect. The number, concentration, and size of the microbubbles all independently affected (p less than 0.01) peak myocardial videointensity after left atrial injection of contrast on multivariate analysis. Highly concentrated microbubbles (4.4 to 5.1 billion/ml) given during dipyridamole-induced coronary hyperemia was most frequently (88%) associated with myocardial opacification after right atrial injection of contrast and was the best predictor of this result on multivariate analysis (chi 2= 9.01, p = 0.003). No changes were noted in left atrial, left ventricular, and pulmonary artery pressures despite injection of large numbers of microbubbles into the right atrium. CONCLUSIONS: Successful and reproducible myocardial opacification can be achieved during myocardial contrast echocardiography after right atrial injection of contrast. These findings could have far-reaching implications in the use of myocardial contrast echocardiography in acute and chronic ischemic syndromes in humans.

Algorithms↗

PubMed2004

Controlled contrast transcranial Doppler and arterial blood gas analysis to quantify shunt through patent foramen ovale.

BACKGROUND AND PURPOSE: A right-to-left shunt can be identified by contrast transcranial Doppler ultrasonography (c-TCD) at rest and/or after a Valsalva maneuver (VM) or by arterial blood gas (ABG) measurement. We assessed the influence of controlled strain pressures and durations during VM on the right-to-left passage of microbubbles, on which depends the shunt classification by c-TCD, and correlated it with the right-to-left shunt evaluation by ABG measurements in stroke patients with patent foramen ovale (PFO). METHODS: We evaluated 40 stroke patients with transesophageal echocardiography-documented PFO. The microbubbles were recorded with TCD at rest and after 4 different VM conditions with controlled duration and target strain pressures (duration in seconds and pressure in cm H2O, respectively): V5-20, V10-20, V5-40, and V10-40. The ABG analysis was performed after pure oxygen breathing in 34 patients, and the shunt was calculated as percentage of cardiac output. RESULTS: Among all VM conditions, V5-40 and V10-40 yielded the greatest median number of microbubbles (84 and 95, respectively; P<0.01). A significantly larger number of microbubbles were detected in V5-40 than in V5-20 (P<0.001) and in V10-40 than in V10-20 (P<0.01). ABG was not sensitive enough to detect a shunt in 31 patients. CONCLUSIONS: The increase of VM expiratory pressure magnifies the number of microbubbles irrespective of the strain duration. Because the right-to-left shunt classification in PFO is based on the number of microbubbles, a controlled VM pressure is advised for a reproducible shunt assessment. The ABG measurement is not sensitive enough for shunt assessment in stroke patients with PFO.

Adult↗

PubMed1997

A comparison of gaseous emboli release in five membrane oxygenators.

The purpose of this study was to compare the air handling capability of five currently used membrane oxygenators: the Avecor Affinity, the Bentley SpiralGold, the Medtronic Maxima Plus, the Sarns Turbo and the Sorin Monolyth M. A circuit was constructed to include a hardshell venous reservoir and roller pump. Pressure monitoring sites and ultrasonic microbubble detection probes were located proximal and distal to the oxygenator. An air injection/infusion site was provided proximal to the roller pump inlet. Each circuit was primed with fresh anticoagulated bovine blood, adjusted to a haematocrit of 25% and maintained at 38 +/- 1 degree C. Three different bolus amounts of air (10, 20 and 40 cm3) were injected at three blood flow rates (3, 4.5 and 6 l/min). A 1-min infusion of air delivered at 1 ml/s was also administered at three blood flow rates (3, 4.5 and 6 l/min). The hardshell reservoir was also completely emptied at each flow rate to simulate a massive air infusion. At any given blood flow, outlet microbubble counts were usually higher with greater bolus amounts of air. When indexed to the inlet bubble counts, the following average percent microbubbles were released from the outlet: Turbo 25%, Affinity 7%, Monolyth 5%, Maxima 3% and SpiralGold 1%. With a constant air infusion of 1 ml/s, greater outlet microbubble counts were associated with higher blood flow rates. Again, when indexed to the inlet bubble counts, the following average percent microbubbles were released from the outlet: Turbo 44%, Affinity 25%, Maxima 19%, Monolyth 16% and SpiralGold 0%. All oxygenators deprimed when the hardshell reservoir was emptied and all shed microbubbles into the outlet blood except the SpiralGold. The results of this study indicate that air handling is not a simple function of blood flow pattern (i.e. top to bottom versus bottom to top), but also includes dynamics associated with oxygenator design, fibre arrangement and flow resistance.

Animals↗

PubMed2004

Liver tumors: evaluation with contrast-enhanced ultrasound.

The development and clinical introduction of microbubble contrast agents has had a particular impact on the detection and differential diagnosis of liver tumors. The first approach widely employed made use of high-transmission power ultrasound, which destroyed the microbubbles in the process of imaging them. It is particularly successful for those agents that have a liver-specific post-vascular phase because, like liver-specific agents used in other imaging modalities such as magnetic resonance imaging and nuclear medicine, malignancies do not retain the contrast, so they stand out with very high conspicuity. Used this way with color Doppler or variants of it, more subcentimeter lesions can be demonstrated with ultrasound than with computed tomography. However, the destructive nature of this approach meant that continuous real-time scanning was impossible. Two developments allowed this to be redressed: new classes of microbubbles with perfluoro gasses instead of air and the invention of multipulse scanning modes that are sensitive to the nonlinear (harmonic) responses of the microbubbles and suppresses tissue signals. This low-power approach is now used almost exclusively, and it has the advantage of displaying the arterial phase of blood supply to a mass and a later phase when the bubbles are trapped in the sinusoids so that the vascular volume of the tissue is depicted. Malignancies typically show a low signal intensity in this phase, regardless of whether they are hyper- or hypovascular in terms of their arterial supply. This allows them to be detected with high sensitivity and much more easily than the destructive modes allowed. In addition, the arterial supply that can be now depicted in real time has characteristics that allow most benign masses to be distinguished from each other and from malignancies, thus improving specificity. Microbubbles also can be used as tracers to provide functional information that can detect occult metastases and cirrhosis noninvasively.

Acoustics↗

PubMed2006

Targeted therapeutic applications of acoustically active microspheres in the microcirculation.

The targeted delivery of intravascular drugs and genes across the endothelial barrier with only minimal side effects remains a significant obstacle in establishing effective therapies for many pathological conditions. Recent investigations have shown that contrast agent microbubbles, which are typically used for image enhancement in diagnostic ultrasound, may also be promising tools in emergent, ultrasound-based therapies. Explorations of the bioeffects generated by ultrasound-microbubble interactions indicate that these phenomena may be exploited for clinical utility such as in the targeted revascularization of flow-deficient tissues. Moreover, development of this treatment modality may also include using ultrasound-microbubble interactions to deliver therapeutic material to tissues, and reporter genes and therapeutic agents have been successfully transferred from the microcirculation to tissue in various animal models of normal and pathological function. This article reviews the recent studies aimed at using interactions between ultrasound and contrast agent microbubbles in the microcirculation for therapeutic purposes. Furthermore, the authors present investigations involving microspheres that are of a different design compared to current microbubble contrast agents, yet are acoustically active and demonstrate potential as tools for targeted delivery. Future directions necessary to address current challenges and advance these techniques to clinical practicality are also discussed.

Animals↗

PubMed2006

Acoustic response of compliable microvessels containing ultrasound contrast agents.

The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 microm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 microm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 microm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the circumferential stress is predicted to increase. Decreasing the vessel size or the centre frequency increases the circumferential stress. For the two frequencies considered in this work, the circumferential stress does not scale as the inverse of the square root of the acoustic frequency va as in the mechanical index, but rather has a stronger frequency dependence, 1/va.

Acoustics↗

PubMed2007

Experimental investigations of nonlinearities and destruction mechanisms of an experimental phospholipid-based ultrasound contrast agent.

OBJECTIVES: We sought to characterize the acoustical behavior of the experimental ultrasound contrast agent BR14 by determining the acoustic pressure threshold above which nonlinear oscillation becomes significant and investigating microbubble destruction mechanisms. MATERIALS AND METHODS: We used a custom-designed in vitro setup to conduct broadband attenuation measurements at 3.5 MHz varying acoustic pressure (range, 50-190 kPa). We also performed granulometric analyses on contrast agent solutions to accurately measure microbubble size distribution and to evaluate insonification effects. RESULTS: Attenuation did not depend on acoustic pressure less than 100 kPa, indicating this pressure as the threshold for the appearance of microbubble nonlinear behavior. At the lowest excitation amplitude, attenuation increased during insonification, while, at higher excitation levels, the attenuation decreased over time, indicating microbubble destruction. The destruction rate changed with pressure amplitude suggesting different destruction mechanisms, as it was confirmed by granulometric analysis. CONCLUSIONS: Microbubbles showed a linear behavior until 100 kPa, whereas beyond this value significant nonlinearities occurred. Observed destruction phenomena seem to be mainly due to gas diffusion and bubble fragmentation mechanisms.

Contrast Media↗

PubMed2003

Gene transfer with echo-enhanced contrast agents: comparison between Albunex, Optison, and Levovist in mice--initial results.

PURPOSE: To determine if commercially available echo-enhanced microbubble contrast agents could be used to increase gene transfection efficiency by means of relatively low-intensity ultrasound-mediated microbubble destruction in skeletal muscles. MATERIALS AND METHODS: Three types of ultrasound microbubble contrast agents (0.01 mL of albumin [Albunex] and human albumin [Optison] and 10 mg/mL of SH U 508A [Levovist]) were each separately mixed with the reporter plasmid DNA (25 microg) encoding green fluorescent protein (GFP) prior to intramuscular injection into the quadriceps muscle of a mouse thigh bilaterally (seven mice per contrast agent). One of the muscle sites that was injected with plasmid DNA was irradiated with low-intensity therapeutic ultrasound (1 MHz) at an intensity of 2.0 W/cm2 for 2 minutes. Mice were sacrificed 7 days after ultrasound treatment for gene expression assay. The number of GFP-expressing muscle fibers was counted. Statistical significance was determined with a two-tailed Student t test. P <.05 was considered to indicate statistically significant difference. RESULTS: Muscle tissue exposed to ultrasound with air-filled Albunex or Levovist microbubbles revealed no difference in the number of GFP-expressing muscle fibers compared with the control non-ultrasound-exposed muscle. Albumin-coated octafluoropropane gas-filled Optison microbubbles showed a 10-fold increase in the number of GFP-expressing fibers (P <.05). CONCLUSION: Low-intensity ultrasound with echo-enhanced Optison induced efficient gene transfer unlike that with Albunex or Levovist.

Albumins↗

PubMed2026

Differential gene transcription following intravenous injection of air bubbles in rats with varying resistance to decompression sickness.

Decompression sickness (DCS) is a pathology caused by the appearance of gas emboli in the bloodstream and tissues. However, the weak correlation between the amount of venous gas emboli (VGE) and the development of DCS, as well as the considerable interindividual variability in DCS susceptibility, suggests that a higher DCS resistance could be associated with a better management of VGE-induced stress. To study the effects of VGE independently of the hyperbaric stress induced by diving, Wistar and DCS-resistant male and female rats received 5 mL/kg of a 0.9% NaCl solution containing air microbubbles through the tail vein. After 120 min, the liver and lungs were harvested. Wet-to-dry weight ratio was determined in the lungs. Gene expression was quantified by reverse transcription-polymerase chain reaction in the liver. Compared with standard Wistar, DCS-resistant rats exhibited a lower lung wet-to-dry weight ratio after air microbubble injection, suggesting lower pulmonary fluid accumulation. In the liver, DCS-resistant rats showed higher tissue factor transcription at the basal state and post-air microbubble injection. Tissue factor pathway inhibitor was lower in DCS-resistant rats at the basal state but higher following air microbubble injection. Levels of heat shock protein 70 (HSP70), heat shock protein 27 (HSP27), and early growth response 1 (Egr-1) were higher in DCS-resistant rats after air microbubble injection. At the basal state, only HSP27 was higher in DCS-resistant rats, with HSP70 lower and Egr-1 not different. These results help clarify the pathways involved in the response to VGE and highlight potential mechanisms underlying resistance to DCS, including enhanced anticoagulant pathways and improved cellular stress responses.NEW & NOTEWORTHY This study suggests for the first time that DCS resistance may be associated with a better tolerance to VGE. This greater DCS resistance could be achieved through improved control of the procoagulant effects of bubbles via TFPI-dependent inhibitory mechanisms and an enhanced cellular stress response to VGE by HSP70, HSP27, and EGR-1. It also suggests that it may be possible to stratify the individual DCS risk based on the thromboinflammatory response to bubbles.

Animals↗

PubMed2004

Ultrasonic drug delivery--a general review.

Ultrasound has an ever-increasing role in the delivery of therapeutic agents, including genetic material, protein and chemotherapeutic agents. Cavitating gas bodies, such as microbubbles, are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilise cell membranes and disrupt the vesicles that carry drugs. Thus, the presence of microbubbles enormously enhances ultrasonic delivery of genetic material, proteins and smaller chemical agents. Numerous reports show that the most efficient delivery of genetic material occurs in the presence of cavitating microbubbles. Attaching the DNA directly to the microbubbles, or to gas-containing liposomes, enhances gene uptake even further. Ultrasonic-enhanced gene delivery has been studied in various tissues, including cardiac, vascular, skeletal muscle, tumour and even fetal tissue. Ultrasonic-assisted delivery of proteins has found most application in transdermal transport of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; and makes cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has on cells and drug-carrying vesicles.

Animals↗

PubMed2006

Bubble dynamics involved in ultrasonic imaging.

In clinical ultrasound, blood cells cannot be differentiated from surrounding tissue, due to the low acoustic impedance difference between blood cells and their surroundings. Resonant gas bubbles introduced in the bloodstream are ideal markers, if rapid dissolution can be prevented. Ultrasound contrast agents consist of microscopically small bubbles encapsulated by an elastic shell. These microbubbles oscillate upon ultrasound insonification. Microbubbles with thin lipid shells have demonstrated highly nonlinear behavior. To enhance diagnostic ultrasound imaging techniques and to explore therapeutic applications, these medical microbubbles have been modeled. Several detection techniques have been proposed to improve the detectability of the microbubbles. A new generation of contrast agents, with special targeting ligands attached to the shells, may assist the imaging of nonphysical properties of target tissue. Owing to microbubble-based contrast agents, ultrasound is becoming an even more important technique in clinical diagnostics.

Blood Cells↗

PubMed1984

Two-dimensional contrast echocardiography. I. In vitro development and quantitative analysis of echo contrast agents.

To facilitate the passage of echo contrast agents through the microcirculation and the echocardiographic study of myocardial perfusion, ultrasonic energy (sonication) was employed to produce contrast agents consisting of relatively uniform, stable and small (less than 10 mu diameter) gaseous microbubbles suspended in liquid solutions. The size and persistence of the microbubbles was verified by light microscopy and an in vitro system were employed for comparative assessment of peak echo amplitude and echo persistence characteristics of various contrast agents. The study indicated that although a variety of hand-agitated and sonicated contrast agents provided satisfactory echo intensities, sonication was clearly superior to the hand-agitation method, because sonication produced smaller, more uniform and more stable microbubbles that may be suitable for myocardial contrast echocardiography. It is concluded that of the contrast agents examined, sonicated solutions of sorbitol (70%) and dextrose (70%) appeared to have particular potential because of the small sizes of the microbubbles (6 +/- 2 and 8 +/- 3 mu, respectively) and their prolonged in vitro persistence. The use of sonication to produce standardized, small and stable microbubbles should facilitate physiologic passage of the contrast agent through the capillary beds and allow two-dimensional imaging of the left heart myocardium during right-sided, aortic root, coronary sinus or intracoronary contrast injections.

Contrast Media↗