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PubMed1989

Myocardial perfusion imaging by contrast echocardiography with use of intracoronary sonicated albumin in humans.

Sonicated albumin has been proposed as a near ideal echocardiographic contrast agent with little myocardial toxicity or hemodynamic effect. Its use has not yet been reported in humans, partly because of difficulties in preparation. With use of the newly modified sonication method, 10 ml of 5% albumin was sonicated for 75 s with a 5.0 ml slow infusion of air. This resulted in microbubbles with a mean diameter (+/- SD) of 5 +/- microns). Fourteen patients undergoing routine coronary angiography were studied. One patient had normal coronary arteries; the other 13 had significant coronary artery disease. In a subgroup of nine patients, sonicated albumin and sonicated diatrizoate meglumine sodium (microbubble diameter 9 +/- 3 microns) were injected several minutes apart, using the same technique. Videodensity-time curves were obtained from a region of interest in the myocardium. Corrected peak contrast intensity (baseline contrast intensity subtracted from peak contrast intensity, gray scale U/pixel) for sonicated albumin and for sonicated diatrizoate meglumine sodium was 51 +/- 26 and 52 +/- 19, respectively (p = 0.89). Washout half-time (T1/2) for the two agents was 5.5 +/- 4.5 and 16.0 +/- 12.2 s, respectively (p = 0.01). One patient with unstable angina experienced transient chest pain after repeated albumin injections. No electrocardiographic changes, blood pressure changes or wall motion abnormalities were observed. Administered by intracoronary injection, sonicated 5% albumin is a safe and effective echocardiographic contrast agent for myocardial perfusion imaging, yielding excellent myocardial contrast with physiologic washout time.

Adult↗
PubMed1990

Intravenous contrast echocardiography with use of sonicated albumin in humans: systolic disappearance of left ventricular contrast after transpulmonary transmission.

The transmission of echocardiographic contrast medium and the cyclic changes in left ventricular videodensity during transpulmonary contrast echocardiography were investigated in nine adult volunteers with the use of intravenous injections of sonicated albumin (microbubble size 5.2 +/- 2.6 microns). Right and left ventricular and myocardial contrast were quantitated by videodensitometric analysis. The injections caused no symptoms, and no hemodynamic or electrocardiographic changes were observed. All injections resulted in right ventricular contrast. Mean peak right ventricular videodensity was 75 +/- 48 at end-diastole and 61 +/- 36 gray scale U/pixel at end-systole (p less than 0.05). Seventy-eight percent of injections resulted in left ventricular contrast with a mean peak videodensity of 21 +/- 33 gray scale U/pixel. Early systole was associated with a rapid decrease in left ventricular contrast intensity with near total disappearance of contrast by end-systole (from 23 +/- 33 and 17 +/- 23 U/pixel at end-diastole to 6 +/- 10 and 3 +/- 2 at end-systole at the left ventricular base and apex, respectively; p less than 0.05). None of the injections resulted in myocardial contrast enhancement by visual or quantitative analysis. Thus, left ventricular contrast echocardiography can be achieved after intravenous injections of sonicated albumin. Transpulmonary left ventricular contrast echocardiography is associated with near total disappearance of contrast during systole. This may be secondary to the destruction of microbubbles by the high left ventricular systolic pressure. These findings may help explain the limited success of this technique thus far for myocardial perfusion imaging.

Adult↗
PubMed1992

Clinical application of transpulmonary contrast-enhanced Doppler technique in the assessment of severity of aortic stenosis.

OBJECTIVE: The aim of this study was to demonstrate the clinical usefulness of the transpulmonary contrast-enhanced Doppler technique by using it to assess the severity of aortic stenosis. BACKGROUND: Sonicated albumin microbubbles can pass through the pulmonary circulation after peripheral venous injection and have been reported to enhance Doppler signals from the left side of the heart. Therefore, their use to determine aortic flow velocity would facilitate the assessment of the severity of aortic stenosis. METHODS: Twenty-two patients with aortic stenosis and seven normal volunteers were examined. Aortic flow velocity was recorded with continuous wave Doppler technique from an apical window before and after injection of 2 ml of sonicated albumin. RESULTS: In 10 patients with aortic stenosis, the aortic velocity envelope was too indistinct to determine the peak velocity before sonicated albumin was injected. After injection, the aortic flow Doppler signal was enhanced in 9 of the 10 patients and the velocity envelope became clear enough to measure the peak velocity, enabling calculation of the transaortic pressure gradient. In the remaining 12 patients with aortic stenosis and in all 7 normal volunteers, the velocity envelope was clear before injection and became much clearer after injection. The calculated transaortic pressure gradient showed a good agreement with catheterization measurements (y = 1.1x-6.5, r = 0.88, p less than 0.001, SEE = 16 mm Hg, n = 13). Duration of Doppler signal enhancement was measured as the time during which the envelope was clearer than before injection throughout the ejection period. The duration was significantly shorter in patients with aortic stenosis than in normal volunteers (16 +/- 5 vs. 52 +/- 32 s, p less than 0.01). There was a significant correlation between left ventricular systolic pressure measured by catheterization and the duration of signal enhancement (r = -0.69), suggesting that albumin microbubbles were fragile at high pressure. CONCLUSIONS: The transpulmonary contrast-enhanced Doppler technique using sonicated albumin is useful for assessing the severity of aortic stenosis even in patients with poor Doppler recordings, although the duration of signal enhancement might be affected by left ventricular systolic pressure.

Aortic Valve Stenosis↗
PubMed1993

Myocardial contrast echocardiography has the potential for the assessment of coronary microvascular reserve.

Coronary vasodilators increase coronary flow by increasing myocardial blood volume. Diseases affecting the coronary microvasculature will affect vasodilator-induced changes in coronary flow by inhibiting changes in myocardial blood volume. In such cases, when myocardial time-intensity curves after administration of a vasodilator are compared with those at baseline, a less than anticipated increase in microbubble transit rates will be noted. As long as we understand what we are measuring in the context of where and how we inject the bubbles, we can begin to define the role of myocardial contrast echocardiography in assessing changes in coronary microvascular reserve. It is also conceivable that because myocardial contrast echocardiography can assess changes in myocardial flow/volume relations rather than just changes in flow, this technique could be used to provide additional insights into the mechanisms of action of different coronary vasodilators and into the pathophysiology of various diseases affecting the coronary microvasculature. Finally, with the advent of commercially available microbubbles, robust on- and off-line analysis algorithms and intracardiac imaging, myocardial contrast echocardiography may become an invaluable adjunct to coronary angiography for determining the pathophysiologic significance of coronary disease in individual patients.

Contrast Media↗
PubMed2005

Myocardial contrast echocardiography accurately reflects transmurality of myocardial necrosis and predicts contractile reserve after acute myocardial infarction.

BACKGROUND: Both myocardial contrast echocardiography (MCE) and cardiovascular magnetic resonance (CMR) can identify myocardial necrosis after acute myocardial infarction (AMI). However, transmural extent of infarction (TEI) correlates of myocardial perfusion by MCE after AMI are unknown. We sought to ascertain the ability of MCE to (1) predict TEI as defined by contrast-enhanced CMR and (2) to compare the relative accuracy of these techniques to predict contractile reserve late after AMI. METHODS: MCE and CMR were performed in 42 patients with AMI 7 to 10 days after thrombolysis. Contractile reserve with low-dose dobutamine was evaluated 12 weeks after revascularization. RESULTS: Both qualitative (myocardial contrast intensity) and quantitative MCE [peak contrast intensity, microbubble velocity (beta), and myocardial blood flow] showed a significant (P < .0001) inverse relationship with increasing TEI. However, beta was the single best predictor of TEI (P = .002). Both qualitative MCE and CMR predicted contractile reserve similarly (area under receiver operating characteristic curve were 0.84 and 0.80, respectively). Qualitative and quantitative MCE parameters as well as CMR correlated significantly with the degree of contractile reserve (P < .001). Multiple logistic regression analysis using clinical, electrocardiographic, MCE, and CMR parameters showed that both MCE (OR = 0.03, 95% CI 0.01-0.10, P < .001) and CMR (OR = 0.11, 95% CI 0.04-0.26, P < .001) are independent predictors of contractile reserve. The most discriminative quantitative parameters for prediction of contractile reserve were microbubble velocity (P < .001) and myocardial blood flow (P = .001) assessed by MCE. CONCLUSION: MCE reflects the transmural extent of AMI as assessed by CMR. Both techniques predict contractile reserve.

Echocardiography↗
PubMed2004

Early impairment of myocardial blood flow reserve in men with essential hypertension: a quantitative myocardial contrast echocardiography study.

OBJECTIVE: Aims of this study were to: (1) demonstrate whether quantitative myocardial contrast echocardiography could detect an index of myocardial blood flow reserve through the analysis of refilling curves generated by microbubble transit into myocardium both at rest and after vasodilatation induced by dipyridamole; and (2) explore with this method myocardial microcirculatory function in two different models (ie, patients with essential hypertension and control subjects). METHODS: Two groups of strictly age-matched men were studied (case-control study): 12 patients who were adults (28.2 +/- 0.2 years) and asymptomatic with never-treated essential hypertension, a mild degree of left ventricular hypertrophy, and normal left ventricular function; and 12 control subjects. Quantitative myocardial contrast echocardiography was performed in all study participants. We used second-generation ultrasound microbubbles as echocardiography contrast agent. Real-time color-coded power modulation was performed with a phased-array system interfaced to a S3 transducer (1.3-3.6 MHz). RESULTS: In control subjects there was little increase in myocardial blood volume (30%) between basal and hyperemic status (P <.05); in patients with hypertension this parameter increased by 22% (P <.05). Myocardial blood velocity increased after dipyridamole by 270% in control subjects (P <.01), whereas for patients with hypertension this parameter increased only by 150% (P <.02). The index of myocardial blood flow reserve was significantly lower for patients with hypertension than in control subjects (3.3 +/- 0.3 vs 4.4 +/- 0.3, respectively; P <.01). CONCLUSION: Results of our study documented that myocardial microcirculation in young adult patients with hypertension showed an early impairment in the vasodilatation capacity of the resistance arterioles under dipyridamole-induced hyperemia, as demonstrated by a reduction of myocardial blood flow reserve. Myocardial blood velocity increased after dipyridamole induction in control subjects, whereas patients with hypertension showed a significantly lesser increase. Myocardial blood flow reserve was significantly lower for patients with hypertension because of an early impairment in vasodilatation capacity of resistance arterioles under dipyridamole-induced hyperemia.

Adult↗
PubMed2006

Quantification of myocardial perfusion using intravenous myocardial contrast echocardiography in healthy volunteers: comparison with positron emission tomography.

BACKGROUND: Intravenous myocardial contrast echocardiography (ivMCE) has the potential to evaluate myocardial contraction and perfusion simultaneously. The purpose of this study was to assess quantification of myocardial blood flow (MBF) using ivMCE and to compare this with MBF as measured with positron emission tomography (PET). METHODS: A total of 16 healthy volunteers underwent ivMCE using power pulse inversion and contrast agent microbubbles at rest and during pharmacologically induced vasodilation. Microbubble destruction was achieved with a burst of high-energy ultrasound, followed by imaging of contrast replenishment with low-energy ultrasound. Regions of interest were drawn and time intensity curves were calculated that were fitted to a monoexponential function. An estimate of MBF (perfusion estime) was calculated as the product of the plateau value A and the exponential beta describing the replenishment curve. MBF was measured with PET using oxygen-15-labeled water at rest and during adenosine stress. RESULTS: Significant correlations were found between MBF as measured with PET and perfusion estimate as measured with ivMCE in the left anterior descending coronary artery (r = 0.87, P < .01), right coronary artery (r = 0.66, P < .01), and left circumflex artery (r = 0.75, P < .01) territories. Heterogeneity, however, was significantly larger for ivMCE (coefficient of variation 32 +/- 15%) than for PET (9 +/- 6%) measurements (P < .01). CONCLUSION: Perfusion parameters as measured with ivMCE correlated with PET-derived MBF, but associated heterogeneity was significantly larger. Currently, this heterogeneity precludes true quantification of MBF using ivMCE.

Adult↗
PubMed2005

Potential clinical applications of myocardial contrast echocardiography in evaluating myocardial perfusion in coronary artery disease.

Myocardial contrast echocardiography (MCE) is a relatively new technique that uses microbubbles to produce myocardial opacification. Recent advances in echocardiography have resulted in improved detection of microbubbles within the myocardium allowing combined acquisition of function and perfusion data, thus making MCE suitable for bedside use. Regardless of the imaging modality chosen or the type of stress used, MCE detects changes developing in the coronary microcirculation, providing important information for the evaluation of severity of coronary artery disease and for the detection of viable myocardial tissue in acute or chronic coronary artery disease.

Coronary Artery Disease↗
PubMed2006

Gushing in canned beer: the effect of ultrasonic vibration.

Everybody has had the experience of a canned carbonated drink overflowing and soiling their clothes. It is difficult to guess the amount of overflow before opening the can, although the phenomenon can be simply explained as the result of the formation of gas bubbles. In this article, we report the surprising result that intensive shaking using ultrasonic vibration can calm this effect in beer. These experiments showed evidence of a memory effect in liquid. The 'calming down' is due to a fine balancing act between a change in the amount of microbubbles (or embryos) and a change in the pattern of their size distribution. Our experimental evidence shows that modification of the pre-existing microbubbles noticeably influences the subsequent nucleation, and this may open a new route to nucleation studies.

Journal Article↗
PubMed2006

Gene delivery by combination of novel liposomal bubbles with perfluoropropane and ultrasound.

Microbubbles and ultrasound have recently been investigated with a view to improving the transfection efficiency of non-viral gene delivery systems. However, microbubbles are unstable and their targeting ability is insufficient for clinical use. To circumvent these problems, we developed novel polyethyleneglycol (PEG) modified liposomes (Bubble liposomes) containing perfluoropropane, which is an ultrasound imaging gas. Here, we used ultrasound to induce cavitation in Bubble liposomes and then investigated their ability to deliver genes in vitro and in vivo. Bubble liposomes could deliver plasmid DNA to many cell types without cytotoxicity. Additionally, in vivo gene delivery, Bubble liposomes were more effective delivery into femoral artery than lipofection method. Thus, Bubble liposomes might be efficient and novel non-viral tools for gene delivery.

Animals↗
PubMed2005

Microfoam sclerotherapy.

Sclerosant microfoam is composed of microbubbles of room or air carbon dioxide (CO(2)). When air is mixed into the surfactant liquid sclerosant, microbubbles of reduced diameter can be obtained of sufficient stability to be injected into the vessels. The area of liquid on the surface is enormously increased in inverse proportion to the diameter of the bubble. Polidocanol in microfoam form displaces the blood from the vessel, permitting homogeneous contact between the sclerosant and the endothelium and facilitating endothelial destruction, and is visible in real time by ultrasonography. The concentration and volume of microfoam can be adjusted according to the disease treated. In the case of home-made foams, however, the volume of gas that can be injected is limited by the low solubility of nitrogen, and only the concentration can be modified. CO(2) is a nontoxic and highly soluble physiological gas, and large amounts can be administered. Here, we report the technique and long-term outcomes of ultrasound-guided injection of polidocanol microfoam in the treatment of large varicose long saphenous veins, postsurgical recurrence varicose veins, varicose ulcers, and venous vascular malformations.

Female↗
PubMed2005

Intrahepatic venous anastomosis formation of the right liver in living donor liver transplantation: evaluations by Doppler ultrasonography and pulse-inversion ultrasonography with Levovist.

BACKGROUND: Our aim was to investigate the development of intrahepatic venous anastomoses between the middle hepatic vein (MHV) and the right hepatic vein (RHV) in adult-to-adult, living donor, liver transplantation. METHODS: Using Doppler ultrasonography, we studied the formation of venous anastomoses between the MHV tributaries for segments 5 and 8 (V5, V8) and the RHV in the liver remnants of 7 donors of a left liver, including the MHV, and in the liver grafts of 8 recipients of a right liver, without including the MHV. In 1 donor and 5 recipients, we performed pulse-inversion ultrasonography with a microbubble contrast agent to evaluate hepatic parenchymal perfusion in the drainage region of the MHV. RESULTS: We observed 15 MHV tributaries of V5 and 13 of V8 among the 15 adult transplant patients. During the first postoperative week, we detected venous anastomosis between V5 and the RHV in 4 patients and in 10 patients between V8 and the RHV. After the 1st week, we observed the formation of anastomosis between V5 and the RHV in 10 patients, and between V8 and the RHV in 3. In both MHV tributaries, the mean flow velocities increased (P < .01). By the end of the 1st week, the formation rate in V8 was higher than in V5 (77% vs 27%, P < .03). In the parenchymal phase of the pulse-inversion ultrasonography with the microbubble contrast agent, the V5 drainage region had low intensities, while the V8 drainage territory revealed high intensities in 4 of 6 patients (66.7%). CONCLUSIONS: Functional venous anastomoses between either V5 or V8 and the RHV developed in most of the donors of left hepatic lobes and in recipients of right hepatic lobes; however, anastomoses developed earlier in V8 than in V5. Furthermore, perfusion was decreased in the drainage area of V5, compared with V8.

Adolescent↗
PubMed2004

Quantification of perfusion of liver tissue and metastases using a multivessel model for replenishment kinetics of ultrasound contrast agents.

Low-MI (mechanical index) ultrasound allows real-time observation of replenishment kinetics after destruction ("flash") of ultrasound contrast agents (USCA). We developed an examination protocol and a mathematical model to quantify perfusion of liver tissue and hepatic metastases. Using a modified multivessel model, we attempted a consistent, physiological description of microbubble replenishment in liver tissue. Perfusion parameters were calculated, separately for the arterial and portal venous phase of liver perfusion, using an i.v. bolus injection of 2 x 2.4 mL SonoVue. The model was evaluated for 10 examinations of liver metastases using flash/low-MI imaging. In contrast to the established, exponential model, the new model consistently describes the sigmoid replenishment of USCA measured in vivo, using flash/low-MI imaging. Parameters for blood volume, blood velocity and blood flow in liver tissue and metastases can be calculated during the arterial and the portal venous phase after a CA bolus injection. The median arterial perfusion in the examined liver metastases was more than 2.5 times higher than in normal liver tissue, whereas the median perfusion during the portal venous phase was more than five times higher in the liver tissue than that in metastases. Microbubble replenishment measured with flash/low-MI US techniques can be consistently analyzed using the multivessel model, even after a bolus injection of USCA. This allows for the quantification of perfusion of liver tissue and hepatic metastases and provides promising parameters of tissue viability and tumor characterization.

Arteries↗
PubMed1997

Relation of contrast echo intensity and flow velocity to the amplification of contrast opacification produced by intermittent ultrasound transmission.

Intermittent ultrasound transmission during contrast echocardiography, so-called transient response imaging (TRI), amplifies contrast intensity. This effect of TRI is attributed to decreased microbubble destruction by reduced exposure time to ultrasound energy. The present study examined the hypothesis that the signal amplification produced by TRI is related to the baseline intensity present in the image and the velocity of flow. We performed second harmonic (2.5/5.0 MHz) imaging during both continuous (frame rate 55 Hz) and electrocardiogram-triggered TRI mode. Contrast images produced by perfluorohexane microbubbles (AF0150) in a steady flow model were obtained every minute throughout the decay phase at transit velocities of 8.1, 6.2, 3.4, 1.9, and 0.7 cm/sec. The decay of videointensity over time could be fitted to a sigmoid curve for both imaging modes with r > 0.99 for individual velocities. The intensity with TRI was greater than that with continuous imaging (CI) at any time and velocity. The mean increase in intensity between modes throughout decay was 8.2 +/- 3.7, 12.8 +/- 4.2, 25.7 +/- 5.8, 49.5 +/- 8.0, and 64.0 +/- 14.4 gray levels for the respective velocity levels studied (p < 0.0001). Although varying with baseline intensity at early and late phases, the TRI amplification plateaued during middecay, and within the intensity range of 16 to 143 gray levels for CI and 67 to 186 gray levels for TRI, it showed no overlap among the different velocity levels. Thus the ability of TRI to enhance contrast opacification is much greater at low flow velocities, which has implications regarding the mechanism of TRI effect and preferential visualization of intramyocardial coronary arteries by this agent. Although this effect was influenced by the baseline intensity, it was relatively constant for each velocity level within an optimal intensity range during middecay, providing the basis for flow velocity measurement by contrast echo.

Blood Flow Velocity↗
PubMed2000

Preliminary clinical experience in cardiology with sonazoid.

Sonazoid (formerly NC100100) is a new ultrasound contrast agent for intravenous injection developed by Nycomed-Amersham. It consists of perfluorocarbon microbubbles that are stabilized with a surfactant and are within a well-defined size range (median diameter approximately 3 microm). Due to the low diffusibility and blood solubility of the gas, the controlled size distribution of the microbubbles, and the flexibility of the shell, Sonazoid is a free-flowing tracer capable of crossing the pulmonary capillary bed after peripheral intravenous injection. It is stable enough for the duration of the ultrasound examination and provides echo enhancement useful for clinical requirements. The preliminary clinical experience in cardiology indications, including its use in reducing the frequency of inadequate echocardiographic studies in patients with suboptimal echocardiograms, and its use as a myocardial perfusion agent in the setting of acute myocardial ischemia is briefly discussed.

Angioplasty, Balloon, Coronary↗
PubMed2002

Instrumentation for contrast echocardiography: technology and techniques.

Contrast echocardiography is the only clinical imaging technique in which the imaging modality (ultrasound) can cause a change in the contrast agent (microbubbles). The change in the contrast agent can range from small oscillations of the microbubbles at a low mechanical index to their disruption at a high mechanical index. The specific mechanical index required to produce these various effects may be different for each contrast agent, depending on the bubble dimension as well as shell and gas characteristics. These alterations in bubbles result in changes in ultrasound backscatter that are specific for the bubbles themselves, rather than for tissue, and are therefore exploited for imaging their presence in tissue. These signal-processing techniques have resulted in an increased signal-to-noise ratio from bubbles vis-à-vis the tissue and have made online assessment of myocardial perfusion possible.

Contrast Media↗
PubMed2002

Contrast enhanced vascular three-dimensional ultrasound imaging.

In other imaging modalities three-dimensional (3D) data displays are well established; not so in ultrasound. Due to the real-time requirements of ultrasound the time available to compute 3D displays is limited, particularly when flow data is acquired with Doppler techniques. Consequently, it is only recently that improvements in computer processing power have resulted in useful vascular 3D ultrasound scans. Many manufacturers have now implemented free-hand 3D power Doppler capabilities on their scanners. However, to obtain flow signals from smaller vessels associated e.g., with tumor neovascularity, may very well require the introduction of a microbubble based ultrasound contrast agent into the blood stream. Given the up to 30 dB enhancement of Doppler signals produced by the contrast microbubbles quite spectacular vascular 3D images are feasible. Moreover, new contrast imaging techniques, such as harmonic imaging, have now permitted 3D vascular information to be acquired and displayed in grayscale with the associated improvement in resolution. In this paper we will review different aspects of contrast enhanced vascular 3D ultrasound imaging including implementation, contrast specific techniques and in vivo imaging.

Animals↗