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PubMed2006

Imaging of malignant liver masses: characterization and detection.

Noninvasive characterization of focal liver lesions is largely based on their enhancement patterns on contrast-enhanced imaging. The use of microbubble contrast agents combined with specialized ultrasound (US) techniques has significantly expanded the role of US in the diagnosis of focal liver lesions based on their vascularity and specific enhancement features. With the advantage of real-time scanning, contrast-enhanced ultrasound (CEUS) can evaluate small lesions that are indeterminate on computed tomography (CT) or magnetic resonance imaging (MR), because CEUS is far less affected by timing issues. Hepatocellular carcinoma is typically characterized by increased arterial flow with frequent dysmorphic tumor vessels and decreased portal venous flow. However, negative enhancement in the portal phase is often not obvious until late (>2 minutes). On the other hand, metastasis shows prompt brief arterial hypervascularity, with either a rim or diffuse pattern and rapid washout, seen as perfusion defects during the portal venous phase. This pattern of complete rapid washout of metastases within the homogeneously enhanced background liver parenchyma can improve their detection and also improve differentiation from hepatocellular carcinoma or benign focal lesions. All malignant lesions generally show negative enhancement or washout during the extended portal venous phase, and this pattern is useful to differentiate them from benign lesions. Microbubble agents, confined to the intravascular space, may infrequently characterize malignancy by showing washout whereas CT or MR shows persistent enhancement due to interstitial distribution.

Carcinoma, Hepatocellular↗

PubMed2006

Ultrasound radiation force modulates ligand availability on targeted contrast agents.

Radiation force produced by low-amplitude ultrasound at clinically relevant frequencies remotely translates freely flowing microbubble ultrasound contrast agents over distances up to centimeters from the luminal space to the vessel wall in order to enhance ligand-receptor contact in targeting applications. The question arises as to how the microbubble shell might be designed at the molecular level to fully take advantage of such physical forces in targeted adhesion for molecular imaging and controlled therapeutic release. Herein, we report on a novel surface architecture in which the tethered ligand is buried in a polymeric overbrush. Our results, with biotin-avidin as the model ligand-receptor pair, show that the overbrush conceals the ligand, thereby reducing immune cell binding and increasing circulation persistence. Targeted adhesion is achieved through application of ultrasound radiation force to instantly reveal the ligand within a well-defined focal zone and simultaneously bind the ligand and receptor. Our data illustrate how the adhesive properties of the contrast agent surface can be reversibly changed, from stealth to sticky, through the physical effects of ultrasound. This technique can be combined with any ligand-receptor pair to optimize targeted adhesion for ultrasonic molecular imaging.

Animals↗

PubMed2003

Fast high-resolution 3D segmented echo planar imaging for dose mapping using a superheated emulsion chamber.

The superheated emulsion chamber (SEC) consists of superheated droplets of halocarbons in an aqueous gel. The gel resides in a pressure chamber. Brachytherapy sources can be implanted in the SEC for radiation dosimetry studies. Upon irradiation by ionizing radiation, the metastable droplets vaporize to form microbubbles. MRI can be used to determine the distribution of bubbles following irradiation of the SEC. In order to generate sufficient statistical accuracy in the determination of dose distributions around brachytherapy sources, it is necessary to use hundreds of irradiation cycles. Susceptibility-weighted images provide contrast between the gel and the vapor microbubbles. This article describes a 3D, blipped, double-sampled, segmented echo-planar imaging technique for rapidly imaging the SEC at 650 microm isotropic 3D resolution in about 2 min. This method was used with a pressure cycling SEC to acquire hundreds of images in several hours. Results are presented showing the 2D dose distribution generated by an (125)I source as measured in the SEC using this new imaging method.

Brachytherapy↗

PubMed1997

On the Elastic Properties of the Interfaces That Stabilize Gas Cavitation Nuclei

Many important systems feature strongly curved interfaces with low surface tension. Four examples are micelles, emulsions, giant bilayer vesicles, and biological membranes. A fifth is the microbubble nuclei that initiate cavitation in aqueous media. A model describing these nuclei and how they respond to changes in ambient pressure attributes their remarkable resiliency to a surrounding film of surface-active molecules. An independent derivation of this model is obtained in this paper by applying thermodynamic methods formulated recently to describe strongly curved amphiphilic interfaces. This illuminates previous models for microbubble nuclei and provides additional information on the mechanical and thermodynamic properties of interfaces in general. Copyright 1997Academic Press

Journal Article↗

PubMed2001

Vascular and perfusion imaging using encapsulated laser-polarized helium.

In this work, the use of hyperpolarized (HP) 3He for in vivo intravascular imaging on animal is reported. To overcome the problem of the low solubility of helium in blood, we propose an approach based on helium encapsulation in lipid-based carrier agents. The mean diameter of the 3He microbubbles, measured equal to 3.0+/-0.2 microm, makes it possible to conduct in vivo studies. In vitro spectroscopy yielded a longitudinal relaxation time T(1) equal to 90 s and an apparent transverse relaxation time T(2)(*) of 4.5 ms. Angiographic imaging (venous and cardiac cavity visualization), as well as lung perfusion imaging, were demonstrated in rats using intravenous injections of microbubble suspensions. Suitable signal and spatial resolution were achieved. The potential of this technique for lung perfusion assessment was assessed using an experimental animal embolism model. Lung perfusion defects and recovery towards a normal perfusion state were visualized. This study was completed with the demonstration of a new ventilation-perfusion lung exploration method based entirely on HP 3He.

Animals↗

PubMed1998

New ultrasound contrast agents for left ventricular and myocardial opacification.

Until recently, the use of contrast agents with 2-dimensional echocardiography has been limited to the detection of intracardiac shunts or abnormal venous connections. The advent of commercially available transpulmonary contrast agents and progress in imaging technology changed this situation. New indications for contrast echocardiography include improved assessment of ventricular function by endocardial border enhancement and the assessment of myocardial perfusion. The major advantage of novel contrast agents is their persistence in circulation, due to the content of a gas that is poorly soluble in plasma or a specific microcapsule wall composition. These features, in conjunction with advanced imaging techniques (intermittent harmonic imaging, harmonic power Doppler, pulse inversion Doppler) allow the detection of minute amounts of the agents in myocardium. There are more than 10 echocardiographic contrast agents undergoing clinical or late preclinical tests. Apart from commercially available Albunex, Levovist, Optison, such agents as EchoGen, Quantison, NC100100 and PESDA have been successfully used in humans. Initial clinical data demonstrating the feasibility of myocardial perfusion studies in patients have been presented for PESDA, Optison, Quantison and NC100100. Early attempts are being made for therapeutic applications of microbubbles, including ultrasound-intensified thrombolysis, tissue targeting and drug delivery. Rapid progress in microbubble technology and imaging techniques has raised a wide interest of the clinicians for contrast echocardiography, which may soon become an established technique for the evaluation of myocardial perfusion, competitive for radionuclide imaging.

Animals↗

PubMed1999

Wideband harmonic imaging: a novel contrast ultrasound imaging technique.

A novel ultrasonic imaging method, wideband harmonic imaging, for nonlinear imaging of microbubble contrast agents is evaluated. In wideband harmonic mode, two pulses of alternate phase are send out. The image is then processed from the sum of both pulses, resulting in an image of nonlinear scatterers such as microbubbles. A prototype ultrasound system, Siemens Elegra, was evaluated with in vitro investigations and animal trials, using conventional, harmonic and wideband harmonic settings with the galactose based ultrasound contrast agent Levovist. Wideband harmonic imaging offers superior sensitivity for ultrasound contrast agents compared to conventional imaging and harmonic imaging. At low transmit power settings (MI 0. 1-0.5) the nonlinear response is already sufficient to generate a image of the blood pool distribution of Levovist in the rabbit kidney including the microvasculature, with clear delineation of vessels and perfused parenchyma. At high transmit amplitudes, nonlinear tissue response reduced the apparent image contrast between contrast agent and tissue. The results suggest that wideband harmonic imaging is currently the most sensitive contrast imaging technique, maintaining highest spatial resolution. This may add to image quality and offer new clinical potential for the use of ultrasound contrast agents such as Levovist.

Animals↗

PubMed2002

Myocardial perfusion imaging using contrast echocardiography.

BACKGROUND: Intense work during the last two decades has brought forth the use of myocardial contrast echocardiography to the clinical threshold for the diagnosis and evaluation of coronary artery disease. CLINICAL USE: A number of ultrasound contrast agents have been developed that act as red blood cell tracers and display myocardial perfusion when imaged by dedicated ultrasound imaging modalities. A considerable amount of experimental and clinical research has shown that myocardial contrast echocardiography can aid in the recognition of acute and chronic myocardial infarction, viable myocardium, and functionally significant coronary stenoses. Comparison of this technique to nuclear imaging and coronary arteriography has demonstrated excellent diagnostic accuracy in the evaluation of various coronary syndromes. Optimal practice of perfusion imaging requires a thorough knowledge of microbubble characteristics and imaging modalities, as well as good experience in the method. PERSPECTIVES: The technique continues to evolve from intermittent gated examination to real-time perfusion imaging that allows evaluation of both perfusion and functional parameters. The opportunity to target sites of pathology with specially engineered microbubbles could also aid in many therapeutic applications besides diagnostic imaging.

Animals↗

PubMed2004

[Scuba diving and the heart. Cardiac aspects of sport scuba diving].

Diving with self-contained underwater breathing apparatus (scuba) has become a popular recreational sports activity throughout the world. A high prevalence of cardiovascular disorders among the population makes it therefore likely that subjects suffering from cardiovascular problems may want to start scuba diving. Although scuba diving is not a competitive sport requiring athletic health conditions, a certain medical fitness is recommended because of the physical peculiarities of the underwater environment. Immersion alone will increase cardiac preload by central blood pooling with a rise in both cardiac output and blood pressure, counteracted by increased diuresis. Exposure to cold and increased oxygen partial pressure during scuba diving will additionally increase afterload by vasoconstrictive effects and may exert bradyarryhthmias in combination with breath-holds. Volumes of gas-filled body cavities will be affected by changing pressure (Figure 1), and inert gas components of the breathing gas mixture such as nitrogen in case of air breathing will dissolve in body tissues and venous blood with increasing alveolar inert gas pressure. During decompression a free gas phase may form in supersaturated tissues, resulting in the generation of inert gas microbubbles that are eliminated by the venous return to the lungs under normal circumstances. Certain cardiovascular conditions may have an impact on these physiological changes and pose the subject at risk of suffering adverse events from scuba diving. Arterial hypertension may be aggravated by underwater exercise and immersion. Symptomatic coronary artery disease and symptomatic heart rhythm disorders preclude diving. The occurrence of ventricular extrasystoles according to Lown classes I and II, and the presence of atrial fibrillation are considered relative contraindications in the absence of an aggravation following exercise. Asymptomatic subjects with Wolff-Parkinson-White syndrome may be allowed to dive, but in case of paroxysmal supraventricular tachycardia they must refrain from diving. Pacemakers will fail with increasing pressure, but some manufacturers have proven their products safe for pressure equivalents of up to 30 m of seawater, so that patients may dive uneventfully when staying within the 0-20 m depth range. Significant aortic or mitral valve stenosis will preclude diving, whereas regurgitation only will not be a problem. Right-to-left shunts have increasingly gained attention in diving medicine, since they may allow venous gas microbubbles to spill over to the arterial side of the circulation enabling the possibility of arterial gas embolism. Significant shunts thus preclude diving. The highly prevalent patent foramen ovale is considered a relative contraindication only when following certain recommendations for safe diving (Table 2). Metabolic disorders are of concern, since adiposity is associated with both, higher bubble grades in Doppler ultrasound detection after scuba dives when compared to normal subjects, and an increased epidemiologic risk of suffering from decompression illness. In conclusion, cardiovascular aspects are important in the assessment of fitness to dive, and certain cardiovascular conditions preclude scuba diving. Any history of cardiac disease or abnormalities detected during the routine medical examination should prompt to further evaluation and specialist referral.

Coronary Artery Disease↗

PubMed2001

[Determining myocardial perfusion--contribution of contrast echocardiography].

There is great demand for a non-radioactive bed-side method for the assessment of myocardial perfusion by contrast echocardiography, which may gain clinical relevance for diagnostic strategies only with i.v. application of the contrast agent as opposed to the intracoronary application used until recently. This has finally become true after many years of developing left heart contrast agents and more adequate ultrasound acquisition methods. This leads to the question: Where are we now? Myocardial contrast echocardiography yields unique information on the pathophysiology of microcirculation in vivo due to the fact that microbubbles remain strictly intravascular. Experimental and clinical studies using intracoronary contrast application have shown that infarct size and area at risk are depicted with high accuracy and furthermore that reflow vs no reflow phenomena are demonstrated after the revascularization procedure. In addition, presence and prognostic implications of collateralization may be assessed. Microvascular integrity plays an important role for functional recovery after revascularization. The breakthrough to a potentially clinical role of contrast echocardiography is mainly due to the development of new acquisition methods, such as pulse inversion technique, which allow differentiation of the microbubble signature from the surrounding myocardium. Initial publications show good diagnostic accuracy for the assessment of infarct size and area at risk as well as for the reflow vs no reflow phenomena and microvascular integrity, in particular also as follow up after protective interventions to improve microcirculation. Now, it is conceivable to assess relative or absolute changes of myocardial perfusion. This may be achieved by using non-video signals for analysis and by understanding attenuation effects and other artifacts. Further intensive and critical evaluation and standardization of imaging and analysis techniques is required before general clinical acceptance. New insight into the dynamic nature of perfusion, however, may already allow progress in some urgent questions of microvascular protection.

Contrast Media↗

PubMed2005

Pulmonary blood transit time and impaired arterial oxygenation in patients with chronic liver disease.

BACKGROUND: Contrast-enhanced echocardiography (CEE) using agitated saline can detect intrapulmonary vasodilatation (IPVD) in patients with hepatopulmonary syndrome (HPS). We estimated the pulmonary transit time of erythrocytes (PTT) by CEE, using microbubbles, and studied its relationship to arterial oxygenation in chronic liver disease. METHODS: Sixteen patients with chronic liver disease and seven healthy subjects were studied. PTT was defined as the time between opacification of the right atrium and left atrium on CEE, using human serum albumin-air microbubble complexes with a mean diameter of 4 microm (Albunex). IPVD was detected by CEE with agitated saline. Arterial blood gases were analyzed with patients in the supine position, and while they were seated. Cardiac output (CO) was determined by Doppler echocardiography. RESULTS: The mean PTT value for all of the patients was 4.0 +/- 1.4 s. One of the 3 patients who showed IPVD was normoxemic. Mild orthodeoxia was observed in the patients with abnormal alveolar-arterial oxygen difference (A-aDO2) values (>15 mmHg), but not in those with normal A-aDO2 values, or in the healthy subjects. PTT was correlated with PaO2 (r = 0.52; P < 0.05; n = 16) and A-aDO2 (r = -0.54; P < 0.05; n = 16) in the seated position. CO was significantly correlated with PTT (r = -0.62; P < 0.05; n = 15), but not with PaO2 and A-aDO2, in both positions. CONCLUSIONS: PTT may be a useful parameter for evaluating arterial oxygenation in patients with chronic liver disease with early HPS.

Adult↗

PubMed1988

Echocardiographic imaging of the left ventricle by peripheral intravenous injection of echo contrast agent.

With the use of a new echo contrast agent (ECA) that consists of a suspension with microbubbles (100% less than 3.9 micron in a moving system), we were able to opacify the left ventricle by peripheral intravenous injection in 124 of 130 patients (95%) without shunt connection. In 12 patients with aortic valve disease we measured the opacification of the right and left ventricles videodensitometrically by means of increasing doses. Dose 1 (8.7 ml ECA) and dose 4 (50 ml ECA) led to no significant difference in intensity in the right ventricle (168 +/- 32 vs 184 +/- 16 units, respectively; p greater than 0.05); however, opacification of the left ventricle was significantly more evident after dose 4 (60 +/- 60 vs 88 +/- 62 units, respectively; p less than 0.05). On the basis of the farthest distance reached by the regurgitant microbubbles from the aortic valve, the severity of regurgitation was graded on a four-point scale; the results were compared with those of aortography. A significant correlation (r = 0.98, n = 9) was found between ECA grading and aortography in the evaluation of the severity of aortic insufficiency. In addition, flow characteristics in patients with mitral stenosis, aortic insufficiency, and the regurgitation jet in incompetent aortic prosthesis in connection with diastolic inflow over the mitral valve were described. Moreover, it was possible to differentiate between inflow of ECA into the left atrium via an atrial septal defect and across the pulmonary vascular bed. No adverse effects were reported by the patients. Left ventricular end-diastolic volume index, end-systolic volume index, stroke volume index, and ejection fraction were determined before and after intravenous injection of increasing doses of ECA by means of the area-length method of Sandler and Dodge. Even after dose 4 we observed no significant changes in left ventricular function. The values before and after injection were in the range of intra- and interobserver reproducibility. Only three patients reported a slight taste sensation. In nine patients with a history of allergies there were no side effects.

Aortic Valve Insufficiency↗

PubMed1978

Electron microscopic analysis of replicating DNA of sea urchin embryos.

DNA was extracted from Paracentrotus lividus embryos at the third S phase afer fertilization and analyzed with the electron microscope. The most relevant structures observed in this actively replicating DNA are clusters of short, closely spaced microbubbles (about 0.1 micron long on the average), partially or entirely single-stranded molecules and few linear forks. Unexpectedly, no long eye forms were observed. The analysis of DNA purified from gastrulae and from adult somatic tissues has revealed the same structures, although at a low frequency. A quantitative analysis has been carried out to determine the size distribution and spacing of microbubbles. A number of control experiments have been performed to characterize these structures better. Various possiblities are discussed to account for the presence of the observed forms and the absence of larger eyes.

Animals↗

PubMedDate not supplied

Efficacy of Doppler ultrasound [correction of utrasound] for screening symptoms of decompression sickness during simulated extravehicular activities.

Doppler ultrasound is frequently used for monitoring circulating microbubbles during decompression to assess the symptoms of Decompression Sickness (DCS). This analysis was carried out to evaluate its effectiveness for screening symptoms of DCS during simulated extravehicular activities (EVA). The information from various hypobaric chamber studies carried out at the NASA Johnson Space Center, Houston, TX was used in this analysis (n=516). The circulating microbubbles were detected in the precordial area in 42% (218/516), and symptoms were reported in 16% (81/516) of these exposures. The accuracy of Doppler-detectable bubbles (Spencer grades) on all symptoms of DCS was examined by calculating measures of sensitivity and specificity. The efficacy of Doppler as a screening device was examined by calculating their positive predictive value (PPV) and negative predictive value (NPV). The results of these analyses indicated that the sensitivity of Doppler decreased, and the PPV increased with higher Spencer grades. However, the likelihood of detecting true negative cases (NPV) was consistently higher with all bubble grades. Due to the high false-positive rate and low prior probabilities of the risk of DCS, Doppler was found to be more useful to identify those who did not develop DCS, than to detect positive cases of DCS in the simulated EVA exposures.

Decompression Sickness↗

PubMedDate not supplied

Observations of ultrasound-induced effects in the fish Xiphophorous maculatus.

Tails of the fish Xiphophorous maculatus have been studied by transmission light microscopy during irradiation with continuous wave ultrasound (frequencies 0.78-3 MHz, spatial average intensities 0.01-3 Wcm-2). Blood flow started to increase a few minutes after the start of an irradiation, reaching a maximum after 5-10 min. Periodic variations in blood flow rate were often seen, and the response varied considerably among individual specimens. Acoustic microstreaming, which resulted in rapid rotation of clusters of cells, was observed in blood vessels adjacent to cartilaginous rods in the tail. The threshold average spatial intensities to initiate this were a few hundred mW cm-2 at 0.78, 1.5 and 3 MHz. The microstreaming resembled that occurring around ultrasonically stimulated microbubbles, but no evidence of any association was found. Microbubbles, possibly originating in water, were sometimes seen in the tissue of the fish following treatment with ultrasound.

Animals↗

PubMed1993

Myocardial regional blood flow: quantitative measurement by computer analysis of contrast enhanced echocardiographic images.

Quantitation of regional myocardial blood flow constitutes the missing link between the anatomy of coronary obstruction and its physiological effect on regional oxygen supply. Microscopic air bubbles, introduced into the coronary circulation, were shown to produce a transitory enhancement of the myocardial tissue contrast, easily detectable with standard ultrasonic imaging equipment. This study presents a new approach linking the tissue blood flow with the time-dependent changes in the intensity of the ultrasonic reflections produced by the microbubbles. The tissue blood flow is evaluated using the well-known indicator dilution relation, according to which flow equals the ratio between the intravascular fraction of the tissue sample volume and the mean transit time of the contrast agent. We derive these two parameters from the time curves representing the contrast induced variations in the mean videointensity measured in two regions of interest, a reference region in the left ventricular cavity and the region of interest within the myocardial tissue. The intravascular volume fraction is computed as the ratio of the total power of the above two intensity curves, as each of these is assumed to be proportional to the total amount of tracer traversing the corresponding region of interest. The mean transit time is computed using combined time- and frequency-domain processing, involving Fourier deconvolution of the response function of the myocardial tissue sample. This approach was validated in an in vivo model in a series of animal experiments involving left atrial injection of albumin coated air microbubbles (Albunex). Videointensity curves obtained during contrast enhancement of the myocardium were analyzed to provide values of regional myocardial blood flow (in mL/min/100 g) in 45 myocardial regions of interest defined in 7 experiments performed on 4 animals. The values obtained with our approach correlated well (r = 0.77, p < 0.001) with standard reference measurements based on radiolabeled microspheres. The intertechnique variability was found to be smaller than the intersegment variability characterizing our technique. The difference between the mean flow values obtained with microspheres for segments of the entire heart and the mean flow obtained with our technique for all regions of interest ranged between 1 to 19% in the 7 experiments. In its present form, based on left atrial or left ventricular injection of contrast solution, this method may allow, for the first time, quantitative evaluation of myocardial regional blood supply in the cardiac catheterization laboratory or the operation theater.(ABSTRACT TRUNCATED AT 400 WORDS)

Albumins↗

PubMed1988

Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies.

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

PubMed1988

Myocardial contrast echocardiography without significant hemodynamic effects or reactive hyperemia: a major advantage in the imaging of regional myocardial perfusion.

All agents used for myocardial contrast echocardiography to date produce adverse hemodynamic effects and alter coronary blood flow. It was hypothesized that because 5% human albumin, when sonicated for use as a contrast agent, is neither hyperosmolar nor a calcium chelator, it would not have significant effects on coronary blood flow, left ventricular function or systemic hemodynamics. Albumin microbubbles of two distinct sizes (mean size 2.9 and 5.8 micron) were produced and compared with nonsonicated albumin, nonsonicated Renografin, sonicated Renografin and hand-agitated Renografin for their effects on hemodynamics, coronary blood flow and regional left ventricular systolic thickening in 15 open chest anesthetized dogs. None of the albumin solutions significantly altered left atrial, left ventricular systolic and end-diastolic and mean aortic pressures. These agents did not cause a coronary hyperemic response or alter left ventricular systolic thickening, but slightly lowered the peak positive left ventricular maximal rate of rise in pressure (dP/dt) (-4.1 +/- 5.4%, p less than 0.01). In contrast, all the Renografin solutions caused significant changes in all these variables (p less than 0.02). In six dogs. albumin solutions did not alter these variables even in the presence of critical coronary stenosis. The contrast opacification produced by 5.8 micron albumin microbubbles was equivalent to that produced by sonicated Renografin. Compared with an equivalent amount of saline and nonsonicated albumin solutions, 10 ml of sonicated albumin did not produce any evidence of infarction, embolization or hemorrhage in the myocardium, brain or kidneys of rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗